UAB Pathology in Focus Vol. 1 Issue 1

Pathology in focus UAB DEPARTMENT OF PATHOLOGY

UAB Pathology researchers define immune response mechanism describing T cell fate determination

Volume 1, Issue 1 2019

Inside CLINICAL 2 3 3 4 4 5 6

RESEARCH

3 Faculty Join Laboratory Medicine Renowned Pathologist Named New AP Division Director Faculty Awarded for Service to HSF Lab Medicine Names New Directors Anatomic Pathology Adds New Faculty CDC App Aims to Improve Diagnosis Community Practice Pathology Program Expands

15 17 18 19 21 22 24 25 26 27 28 29 30

EDUCATION 7 8 8 9 10 10

Department Celebrates Outgoing Residents and Fellows Welcome Class of 2022 Siegal Named President-Elect of ASCP Trainee Research Day Elaine Jaffe with WHO Delivers Pritchett Lecture Listinsky Lecture Welcomes Glycobiology Expert

AND MORE

31 A Fond Farewell to Dr. Robin Lorenz 32 Conference and Committee Roundup

AWARDS 11 11 12 12 13 13 14

Yemelyanova Named First Hazel Gore Endowed Professor Chen Wins Best Paper Award Pathology Takes Home 3 Argus Awards Marques and Wende Win Dean's Excellence Awards 3 Faculty Earn Promotions Netto Becomes SOM's 3rd Featured Discovery Recipient 2 Faculty Earn Emeritus Status

Immune Response Mechanism Described for Fate Determination of T Cells BĂźttner Lecture Integrates Molecular Pathology and Clinical Oncology Possible Treatment for a Rare, Potentially Deadly, Blood-Clotting Disorder Epigenetic Reprogramming of Hearts Found in Congestive Heart Failure ID of Subgroup of Heart Failure Patients Could Lead to Improved Care Immune Cells Identified that Create and Sustain Chronic IBD Scientists Reverse Aging Symptoms in Mouse Model Magnanimous Gift from Former Pathology Chair Croatian Faculty Visit Department in Research Exchange Inaugural Pilot Awards Support Translational and Clinical Research Big Change from a Small Player UALCAN: Interpreting and Presenting the Growing Pool of Cancer Data TTP Fair Showcases Research Progress

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24 UAB PATHOLOGY IN FOCUS is published by the Department of Pathology in the School of Medicine at the University of Alabama at Birmingham. West Pavilion 210 619 South 19th Street Birmingham, AL 35233-7331 205.934.4303

Chair George Netto, M.D. Editor in Chief Christina Crowe Communications Graphic Design Jane Ehrhardt In High Spirits Creative

Please direct any questions, comments and suggestions to: Christina Crowe phone 205.975.2498 email pathnews@uabmc.edu

Catch up on our latest announcements, news and accomplishments at UAB.EDU/MEDICINE/PATHOLOGY Follow us on Twitter @UABPathology

LE T T E R FRO M TH E C H AI R

WELCOME

TO THE INAUGURAL ISSUE of UAB Pathology In Focus magazine. With a nod to previous departmental newsletters, we hope to reinvigorate the concept with this comprehensive publication in both print and electronic form. As 2018 concluded and a new year begins, we as a Department have many reasons to celebrate. It was a year of growth, with the addition of 8 new faculty members across our 6 divisions this year alone, featured on pages 2 and 4. This includes the addition of a division director in Anatomic Pathology who brings international renown to the department—read more about her on page 3. At the same time, several faculty received promotions, and two achieved emeritus status (pages 13 and 14). As you'll see, we've divided the magazine into four categories: Clinical, covering content in our Anatomic Pathology Division and various labs, including the Community Practice Pathology Program, highlighted on page 6; Education, including several world-renowned experts in their fields visiting us as guest lecturers for our endowed lectureships, including Listinsky and Pritchett lectures (page 10), among others. The Awards section (page 11) covers accolades from across the Department, ranging this year from recognitions by the School of Medicine, to faculty promotions, to professional organizations highlighting our faculty and staff. The Research section (page 15) takes a closer look at some of the many exciting research endeavors currently underway by faculty in our Department. We hope you'll enjoy this inaugural issue of an existing communique in a new format, which builds on communications in our monthly electronic newsletter, website, and social media content. Please send feedback to us at pathnews@uabmc.edu, and let us know what you'd like to see in upcoming issues. This year was one of tremendous growth for the Department, the UAB School of Medicine, and the University. Research grants and award funding topped $500 million in a single year this year, and a $30 million donation to name the O'Neal Comprehensive Cancer Center are among some of the exciting developments. As a Department, we rank 12th for NIH funding among pathology departments nationally. This issue reflects on recent accomplishments; I'm looking forward to another exciting year as chair of this growing department. We have many plans ready to announce in early 2019, which marks the 50th anniversary of the University of Alabama at Birmingham. We hope you'll grow with us as we continue to build on the momentum we've generated and the reputation built by generations of career scientists, doctors, and educators here at UAB.

George Netto, M.D. Professor Robert and Ruth Anderson Endowed Chair UAB Department of Pathology

2019 Vol. 1, Issue 1 | UAB Pathology

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Faculty Join Laboratory Medicine

NEW FACULTY recently joined the Division of Laboratory Medicine, directed by X. Long Zheng, M.D., Ph.D., Robert B. Adams Professor of Pathology.

Sixto M. Leal Jr., M.D., Ph.D.

Bryan Guillory, M.D.

Prabhakara Nagareddy, Ph.D.

SIXTO M. LEAL JR., M.D., PH.D., completed his residency training in clinical pathology at the University of North Carolina, and a medical microbiology fellowship at the Cleveland Clinic. Leal joins the Division as an Assistant Professor, Assistant Director of Clinical Microbiology, and Associate Director of the UAB Mycoplasma Diagnostic Reference Laboratory. He

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is board certified in clinical pathology and medical microbiology with a special interest in mycology, parasitology, mycoplasmology, and histopathologic identification of microorganisms. Leal serves on the CAP Clinical Pathology Education Committee and harbors a significant interest in medical education. He has a basic and translational research background in mycology, immunology, and clinical microbiology and will pursue ongoing research projects focused on the development of novel molecular diagnostic tests for infectious agents and the biology of microbial pathogenesis. BRYAN GUILLORY, M.D., completed his residency in Anatomic and Clinical Pathology at Texas A&M, and a fellowship in Blood Banking and Transfusion Medicine at Yale University. Guillory is board certified in anatomic and clinical pathology. He joins the Division as an Assistant Professor focusing on service in blood banking, apheresis and coagulation. Guillory looks forward to continuing his research in clinical informatics, test utilization, clinical decision support systems, treatment optimization, and artificial intelligence.

PRABHAKARA NAGAREDDY, PH.D., is a principal investigator currently holding R00- and R01-grants from the National Institutes of Health. Broadly, his research focuses on understanding how the so-called “cardiovascular risk factors” actually contribute to cardiovascular disease. Specifically, he has studied the roles of diabetes, obesity, rheumatoid arthritis and other risk factors on atherosclerosis and ischemic heart disease, and published several papers in highimpact journals. Nagareddy is mentoring several postdoctoral trainees, and has received many national and international awards for his research accomplishments. He is an ad hoc reviewer for the Atherosclerosis and Inflammation of the Cardiovascular System (AICS) study section at NIH, US-Israel BNF, UK Diabetes, and many peer-reviewed journals. He has presented numerous invited talks and lectures. “The Division of Laboratory Medicine has gained three outstanding colleagues in Drs. Leal, Guillory and Nagareddy,” Zheng says. “Their wide-ranging clinical and research interests represent the direction in which the division is heading, with faculty specializing in a diverse range of disciplines within the field.”

CL I N I C AL

Renowned Pathologist Named New AP Division Director

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Cristina Magi-Galluzzi, M.D., Ph.D., an internationally recognized pathologist and researcher, has been named director of the Division of Anatomic Pathology in the Department of Pathology. Magi-Galluzzi comes to UAB from the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, where she was professor. She officially joined UAB in October. “Dr. Magi-Galluzzi is renowned in her field, bringing expertise in genitourinary pathology,” said George Netto, M.D., Department Chair. “Her addition to our team will provide renewed leadership for the Division of Anatomic Pathology and enhance our sub-specialized clinical expertise in surgical pathology. Her research focus on prostate, bladder and kidney cancers will further establish our department as a major player in the field of GU pathology.” Magi-Galluzzi takes over the role of Division Director for interim director Vishnu Reddy, M.D. Her clinical expertise is the pathological diagnosis of genitourinary diseases, including prostate, bladder, testicular, adrenal and kidney malignancies. Her research interest focuses on prostate carcinogenesis and in the discovery and

validation of tumor markers and genomic tests of value in furthering the goals of successful treatment and understanding of the pathogenesis of genitourinary diseases. “I am delighted to join the UAB School of Medicine's Department of Pathology and excited about leading a team on collaborative projects,” Magi-Galluzzi said. “I consider myself a pathologist first, and a teacher and researcher second, and my main goal is to provide excellent clinical service to patients.” In September she was named to The Pathologist magazine's 2018 Power List of “100 of the best, brightest and most powerful advocates of pathology.” “As a clinician, I always strive to have a positive impact on the patients' present,” she said. “As a teacher and researcher, making a difference in the patients' future care is also critical to my success and the success of my team.”

Pathology Faculty Awarded for Decades of Service to HSF

30 YEARS

On Friday, June 6, several of our Department Pat Bucy, M.D., Ph.D., Professor, Laboratory Medicine faculty were awarded by the UAB Health Services Foundation for their decades of clinical service at the 25 YEARS Physician Service Awards event. Ona Marie Faye-Petersen, M.D., Professor, Anatomic Pathology Presented by Tony Jones, M.D., Stephen Moser, Ph.D., Professor, Laboratory Medicine COO, Chief Physician Executive; Patricia Vishnu Reddy, M.D., Professor, Anatomic Pathology, Pritchett, Executive Vice President; and Interim Division Director, Neurology Billy Connelley, Senior Associate Vice Casey Weaver, M.D., Professor, Anatomic Pathology President of Ambulatory Services and held at the Kirklin Clinic, the event had a 20 YEARS lighthearted tone as each award recipient was introduced with a witty description of Andra Frost, M.D., Professor, Anatomic Pathology their career at UAB. Robert Hardy, Ph.D., Professor, Laboratory Medicine The Department is proud to Andrew Robinson, Ph.D., Professor, Laboratory Medicine Tony Jones, M.D., (L) President of celebrate each of these well-deserving University of Alabama Health Services Foundation and Chief Physician Executive individuals for their many years of hard of UAB Health System, shares a laugh work in service to UAB Medicine. 2019 Vol. 1, Issue 1 | UAB Pathology 3 with Pat Bucy, M.D., Ph.D.

C L INI C A L

New Lab Directors

Anatomic Pathology

The Division of Laboratory Medicine, under the leadership of Division Director X. Long Zheng, M.D., Ph.D., announces the naming of several new laboratory directors.

IN 2018,

DENIZ PEKER, M.D., Associate Professor of Pathology, Attending Physician in Hematopathology/Surgical Pathology in the Division of Laboratory Medicine APPOINTED director of the Flow Cyotmetry Lab at UAB Hospital, effective October 1, 2018. ALLEN BRYAN, M.D., PH.D., Assistant Professor of Pathology, Attending Physician in Laboratory Medicine, APPOINTED director of the University Emergency Department Laboratory, UAB-POCT, The Kirklin Clinic POCT, UAB Hospital PPM and Callahan Eye Hospital Labs. Dr. Bryan takes over for Pat Bucy, M.D., Ph.D., Professor; Andrew Robinson, Ph.D., Professor; and John Smith, M.D., Professor. Zheng thanks them for their outstanding service to the division. BRYAN GUILLORY, M.D., Assistant Professor of Pathology, Attending Physician of Transfusion Medicine, APPOINTED director of Anesthesia/CICU lab at UAB Hospital. He replaces Marisa Marques, Professor of Pathology, after 20 years of service in this area. Guillory is also appointed assistant director of the Hemostasis Lab at UAB Hospital, working with Dr. Zheng, the director of hemostasis lab. LIYUN CAO, PH.D., Instructor of Pathology, APPOINTED assistant director of the Clinical Chemistry Lab at UAB Hospital, working with Dr. Robert Hardy who is the director of clinical chemistry lab. LANCE WILLIAMS, M.D., Associate Professor of Pathology, Attending Physician of Transfusion Medicine, APPOINTED associate director of the Blood Bank, in addition to his current directorship of Therapeutic Apheresis at UAB Hospital and CPPP transfusion service. SIXTO LEAL, M.D., PH.D., Assistant Professor and Attending Physician of Pathology, APPOINTED as assistant director of the Clinical Microbiology Lab, associate director of the Fungal Lab, and co-director of the Mycoplasma Lab at UAB Hospital. Dr. Leal will be working closely with Dr. Kenneth Waites who serves as the director of the mycoplasma lab. “Congratulations to all of the newly appointed directors and associates for their leadership roles in these important laboratory roles throughout the UAB Hospital and Health System,” Zheng said. “The Department of Pathology is proud to continue to serve at the helm of these key clinical facilities.”

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Adds New Faculty

FIVE

new faculty joined the Division of Anatomic Pathology led by Director Cristina Magi-Galluzzi, M.D., Ph.D., Professor in the Surgical Pathology section. VIRGINIA DUNCAN, M.D., a graduate and chief resident in the UAB Anatomic Pathology Residency, joins the division as Assistant Professor. Board certified in Anatomic and Clinical Pathology, she completed her fellowship in Pediatric and Perinatal Pathology at the University of Washington. Her research interests focus on pediatric pathology; specifically the clinicopathologic aspects of entities spanning the perinatal period from fetus to neonate. DINA KOKH, M.D., is a board certified anatomic and clinical pathologist and cytopathologist. She completed her residency in anatomic and clinical pathology at the University of Maryland, followed by a fellowship in cytopathology. Kokh subsequently pursued a fellowship in gynecologic pathology at Stanford University. Her research interests include gynecologic and breast pathology/cytopathology. Kokh joins the division as an assistant professor. GOO LEE, M.D., PH.D., joins the Division as Assistant Professor in the Surgical Pathology Section and Gastrointestinal Pathology. Lee comes to the Department from the Department of Pathology and Laboratory Medicine at the Ottowa Hospital/University of Ottowa. He is board certified in Anatomic and Clinical Pathology, and has clinical expertise in GI and GYN Pathology. Lee completed a fellowship at Emory University in GI/Hepatic Pathology. His research interests focus on chronic inflammation, molecular pathways, and chemoprevention in inflammatory bowel disease-associated colorectal cancer, as well as early detection of dysplasia in IBD and transepithelial migration of neutrophils in IBD. CONTINUED ON NEXT PAGE

C L I N I C AL

CDC App Aims to Improve Diagnosis, Treatment of Hematologic Disorders Blood clots affect nearly a million Americans each year, according to the Centers for Disease Control and Prevention, and determining the correct type and dosage of an anticoagulant to treat them can be challenging. A new app designed by a multidisciplinary team including Marisa B. Marques, M.D., Professor, Department of Pathology, Division of Lab Medicine, aims to guide the user in lab testing and the administration of anticoagulant drugs. The Anticoagulation Manager (ACM) App is a free mobile app developed by researchers with the CDC and the Georgia Institute of Technology. It serves as a resource for clinicians to assist in the correct dosage and frequency of the appropriate drug for patients with various thrombotic risks or diagnoses. The app walks users through possible patient scenarios, such as “start a patient on anticoagulation” or “reverse a patient's anticoagulation,” then prompts a selection of the patient's condition and provides options based on specific traits of each individual, such as age,

comorbidities, and other medications he or she is taking. “This app was designed with the goal of decreasing the confusion experienced by clinicians when ordering lab tests and choosing or managing a patient's anticoagulation,” Marques said. “Solutions for these challenges will improve utilization of laboratory services and reduce diagnostic and treatment errors and delays.” Marques is one of two pathologists who created the app with the technical assistance of the CDC, along with Michael Laposata, M.D., Ph.D., Professor and Chair of the Department of Pathology at the University of Texas Medical Branch in Galveston. The project is the work of the CDC's Clinical Laboratory Integration into Healthcare Collaborative (CLIHC™), established by the CDC's Division of Laboratory Systems to “develop solutions to optimize the effective use of laboratory services for better patient care,” according to its website. The app was a response to a need for challenges faced by clinicians when choosing and monitoring anticoagulants.

Marques previously worked with Laposata on the development of another app for the CDC called Partial Thromboplastin Time or PTT Advisor, which aims to assist in the ordering and evaluation of a prolonged PTT. “We are excited to be a part of the team designing apps specifically for clinicians, which aim to reduce the rate of errors by assisting with decision-making,” Marques said. “They are easy to incorporate in a physician's existing workflow, while building user confidence.” The apps run on Apple products and are free to download. Visit the CDC's website for more information about CLIHC and the app: www.cdc. gov/csels/dls/clihc.html

DIANA LIN, M.D., joins the division as an assistant professor whose research interests focus on cytopathology and head and neck pathology. This includes molecular characterization of thyroid tumors, specifically focusing on the sequencing of cytologic smears. Lin completed her residency in anatomic and clinical pathology at Rush University Medical Center, and a cytopathology fellowship at the University of Illinois at Chicago. JESSICA TRACHT, M.D., Assistant Professor, is a UAB Pathology graduate who completed a fellowship in cytopathology at UAB and served as chief resident in clinical pathology at our program. Subsequently, she pursued a gastrointestinal pathology fellowship at Emory University. Tracht is interested in clinical research in cytopathology and gastrointestinal tumors. She has a special interest in pancreatic neoplasms, and in developing optimal screening parameters for cervical cancer screening. “We are excited to welcome these incoming faculty to our Division,” said Vishnu Reddy, M.D., Professor, Laboratory Medicine. “Their diverse research interests and expertise build on those of our existing faculty, as we continue to expand the Department's reach.” 2019 Vol. 1, Issue 1 | UAB Pathology

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CLIN I C AL

Community Practice Pathology Program Expands The UAB Department of Pathology expanded its Community Practice Pathology Program (CPPP) in August, reaching deeper into northeast Alabama with the addition of the Riverview Regional Medical Center in Gadsden. “The new relationship between the UAB Department of Pathology and Riverview Regional Medical Center will allow more patients access to high-quality diagnostics,” says Jennifer Gordetsky, M.D., Associate Professor, Anatomic Pathology, UAB Department of Pathology, who serves as Medical Director and Site Chief. The Department provides a full range of anatomic pathology services at the site.

“

It is my pleasure to serve as

part of this effort to bring the excellence associated with UAB Pathology to the patients here in Gadsden. Jennifer Gordetsky, M.D.

Ian Martin, M.D., joins the team as Assistant Professor of Pathology. Faculty performing work at RRMC will be overseen by Walter Bell, M.D., Professor and Chief of the CPPP, and by Gene Siegal, M.D., Ph.D., Professor, Anatomic Pathology and Interim Chair, UAB Department of Genetics. The faculty will be credentialed by the MDSO + Health System Foundation to meet the UAB Standard of Care. Riverview Regional Medical Center is a short-term acute care facility located at 600 South Third Street, Gadsden, AL, opened in 1931. Owned by Prime Healthcare Services (purchased from Community Health Systems March 2015), Riverview has 281 total beds, and 500 Medicare inpatient surgeries per year. Annually, it serves more than 350,000 residents in Etowah and surrounding counties. The volume in surgical pathology procedures prior to UAB Pathology

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enhancing services is 3,500 annually. Expected volume in the next two years, under the expansion program is 6,000 annually. Additional locations where the Department has a community based health system practice throughout the state include: • • • • •

Northeast Regional Medical Center, Anniston Baptist Medical Center East, Montgomery Baptist Medical Center South, Montgomery RMC Stringfellow Memorial Hospital, Anniston Prattville Baptist Hospital, Prattville

The CPPP Program is also supported by UAB Department of Pathology faculty assistant professors Darryl Sanders, M.D., and Manjula Garapati, M.D., in Anniston; and Ian Martin, M.D., Evan Alston, M.D. and Sam Borak, M.D., in Montgomery. These faculty will also help support the UAB Pathology workload. “This program is vital to our support of the community by providing the same quality of service expected at a leading academic medical center like UAB,” said George Netto, M.D., Chair of the Department of Pathology.

BLAZER BOLT 2018

The Department's Forensics Division had a blast running and raising funds for brain cancer research at 2018's Blazer Bolt. L to R: Drs. Daniel Atherton, Daniel Dye, Brandi McCleskey and Gregory Davis, Division Director, Forensics.

EDUCATION Department Celebrates

2018 Outgoing Residents & Fellows The Outstanding Teaching Award for Multidisciplinary & Medical Student Education Award, presented by Ona Marie Faye-Peterson, M.D., Professor, Anatomic Pathology, is voted on by all medical students and trainees and all teaching faculty in the medical school. The awards went to Tiffany Graham, M.D., and Scott Taylor, D.O.

OUR 2018 RESIDENTS & FELLOWS

IT WAS A LOVELY EVENING for a reception on

Thursday, May 24, at the Renaissance Birmingham Ross Bridge Golf Resort & Spa as the Department celebrated its outgoing residents and fellows with a dinner and awards at the 2018 Outgoing Reception. Host James Hackney, M.D., Director of the Pathology Residency Programs, emceed the event which included refreshments and dinner, followed by comments from Chair George Netto, M.D., and the presentation of awards.

faculty awards

Alexander Feldman, M.D., Chief Resident in Anatomic Pathology, presented Frida Rosenblum, M.D., Assistant Professor in Cytopathology, with the Leonard H. Robinson Award for Resident Education in Anatomic Pathology. Joseph Drwiega, M.D., Clinical Pathology Chief Resident, presented Lawrence Williams, M.D., Associate Professor, Laboratory Medicine with the Shu T. Huang Award for Excellence in Laboratory Medicine Education.

resident awards

The Roger Denio Baker Prize in Anatomic Pathology was presented by David R. Baker, J.D., son of Roger, who was the Department's first chair. On December 1, 1944, Roger Denio Baker became the medical school's first full-time faculty member and the first departmental chair appointed by Dean Roy R. Kracke. It is a cash prize of $1,000 given to a resident in recognition of excellence in Anatomic Pathology. Baker, accompanied by his wife, Lois Gaeta Baker and caretaker Ida Russell Webster, presented the award in person to Joseph Drwiega, M.D. The Kracke Award for Best Presentation in Anatomic Pathology was presented by Jennifer Gordetsky, M.D., Associate Professor, Anatomic Pathology, to Zheng Ping, M.D.

The Jay M. McDonald Award for Excellence in Laboratory Medicine, named for former Department Chair Jay McDonald, M.D., was presented by Pat Bucy, M.D., Ph.D., Professor, Laboratory Medicine, to Jeffery Adam Jones, M.D.

chief residents

X. Long Zheng, M.D., Ph.D., Division Director, Laboratory Medicine, announced Erin Baumgartner, M.D., and Vishnu Reddy, M.D, announced David Dorn, M.D.

resident certificates

Drs. Netto and Hackney presented certificates to: Tyler Clemmensen, M.D. (AP/CP) Robin Collingwood, M.D. (AP) Joseph Drwiega, M.D. (AP/CP) Alexander Feldman, M.D. (AP/CP) Zheng Ping, M.D. (AP/CP) Scott Taylor, D.O. (AP/CP)

fellows presentations

• Deniz Peker, M.D., presenting Hematopathology to R. Gabe Koenig, D.O. • X. Long Zheng, M.D., Ph.D., presenting Hemostasis to Elizabeth Staley, M.D., Ph.D. • Shuko Harada, M.D., presenting Molecular Genetic to Diana Morlote, M.D. • Vishnu Reddy, M.D., presenting Surgical Pathology to Erik Kouba, M.D., Ian Martin, D.O., Andrew Martowski, M.D., and Chirag Patel, M.D. • Dr. Reddy also presented Transfusion Medicine to Ashish Manne, M.D.

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E D U C AT ION

Welcome

Class of 2022 Residents & Fellows MATCH DAY 2018 was held around the country on

Friday, March 16, with UAB's Match Day Ceremony taking place at the Alys Stephens Performing Arts Center. The Department is thrilled to announce matches for each of our eight open slots. The students who will join us as the class of 2022 are: Benjamin Ross Daggett Trinity School of Medicine St. Vincent & the Grenadines Mahtab Fakhari University of Kansas School of Medicine Raima Adeel Memon Dow Medical College Pakistan Eric Peter Ollila Medical College of Georgia Augusta University

INTERNATIONAL Medical Graduate (IMG) Residents Abrar Ghurmallah Alghamdi King Abdulaziz University College of Medicine and Allied Sciences Saudi Arabia Mohammaed Abdulgader Sait King Abdulaziz University College of Medicine and Allied Sciences Saudi Arabia

Oraine Damian Smith St. George's University of Medicine Grenada Qing Wei Wuham University School of Medicine China

Siegal Named President-elect of ASCP Congratulations to Gene Siegal, M.D., Ph.D., Interim Chair, Genetics, Robert W. Mowry Endowed Professor and Executive Vice-Chair of Pathology, on being named President-elect of the American Society of Clinical Pathology for 2018-19.

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UAB Pathology proudly welcomed new fellows for the 2018-19 academic year:

Joining us from UAB Tyler Clemmensen 2018-2019 Hematopathology Fellow Robin Collingwood 2018-2019 GI Pathology Fellow Joseph Drwiega 2018-2019 Surgical Pathology Fellow Diana Morlote 2018-19 Hematopathology Fellow Scott Taylor 2018-2019 Surgical Pathology Fellow New to UAB this year David Marbury 2018-2019 Surgical Pathology Fellow. Dr Marbury completed residency at the University of Mississippi. Lindsey Matthews 2018-2019 Surgical Pathology Fellow. Dr. Matthews was a Renal Pathology fellow at the University of North Carolina at Chapel Hill. James Sikora 2018-2019 Transfusion Medicine Fellow. Dr. Sikora comes to us from the University of Florida residency program. Nirupama Singh 2018-2019 Molecular Genetic Pathology Fellow. Dr. Singh completed residency at Brookwood Baptist Health in Birmingham. Yiqin Zuo 2018-2019 Cytopathology Fellow. Dr. Zuo completed a Renal Pathology fellowship at Vanderbilt University.

THE FELLOWS AND RESIDENTS took part

in an orientation program the week of June 25, which included lab management training and meetings with chief residents David Dorn, M.D., Anatomic Pathology and Erin Baumgartner, M.D., Clinical Pathology. We are excited to have these outstanding young doctors join our department!

E DUC AT I ON

13th Annual

AWA RD E E S

Trainee Research Day

Oral Presentations

The annual Department of Pathology Trainee Research Day took place on Wednesday, May 2, in the Hill University Center on the UAB campus.

Chang Hyun Byon – Researcher, Molecular & Cellular Pathology

The event is run by a committee of trainees who assist in its planning and execution, which this year included: Manoja Brahma, Gobinath Shanmugam, Ann Hanna, Dominque Hinshaw, Tshering Lama-Sherpa, Ashish Kurundkar, Jianhua Zhang, Lijia Yu, Shyam Bandari, and Joo Lee and Helen Collins, who also served as event emcees. The event is organized by Rajeev Samant, Ph.D., Professor, Pathology, with support from the Division of Molecular and Cellular Pathology administrative staff Cindy Brown and Kathy Coleman. This exciting event featured morning and afternoon poster sessions, oral presentations by Department trainees, and a Data Blitz of six five-minute presentations. The Keynote Speaker Laurie Harrington, Ph.D., Associate Professor, Department of Cell, Developmental, and Integrative Biology lectured on “My Life with T Cells.” All Pathology graduate students and GBS graduate students (working with Department of Pathology mentors), postdoctoral fellows, residents and other trainees undertaking research in Department of Pathology laboratories were invited to submit abstracts to showcase the vast research undertaken in our Department. Abstracts and posters were judged by an expert faculty panel. Pathology Assistant Professor Craig Maynard, Ph.D., introduced Harrington, a former Department trainee, who spoke on her career path and how she found her way into immunology research. Nearly 100 participants attended the event. “Each year we encourage all trainees to submit abstracts and take advantage of this unique opportunity to share their research with the Department of Pathology research community. Participation in this setting is a great way to gain experience in data presentation to a wide audience,” Samant said.

BET T Y P R I TCH E T T S P E N C E R AWA R D Tshering “Tesh” Lama-Sherpa, Graduate Research Assistant, Cancer Biology, poses with Department Chair George Netto, M.D., (left) after being presented the Betty Pritchett Spencer Award, which provides up to $1,000 toward attending and presenting data at a national scientific meeting related to cancer research. Robert Pritchett, M.D., (right) presented the award, which is named after his sister Betty who passed away in 2008 due to pancreatic cancer.

Daniel Silberger – Postdoctoral Fellow, Anatomic Pathology

Ashish Dhyani Kurundkar – Resident, Pathology Chirag Patel – Fellow, Surgical Pathology Emma Dean – Graduate Student Trainee, M.D./Ph.D. program Ann Hanna – Graduate Research Assistant, Cancer Biology

Data Blitz

Vinayak Khattar – Postdoctoral Fellow, Molecular & Cellular Pathology Kaushlendra Tripathi – Postdoctoral Fellow, Molecular & Cellular Pathology Sumit Agarwal – Postdoctoral Fellow, Anatomic Pathology Kellie Regal – Graduate Student Trainee, Pathobiology & Molecular Medicine Mateus Mota – Graduate Research Assistant, Cancer Biology Bo Chen – Resident, Pathology

Poster Presentations

Jamelle Brown – Graduate Student Trainee, Pathobiology & Molecular Medicine Mark Pepin – Graduate Student Trainee, Biomedical Engineering Yulianna Jimenez – Undergraduate, Biomedical Engineering Diana Morlote – Fellow, Molecular Genetic Pathology Mohammed Rigi – Resident, Pathology Manoja Kumar Brahma –Postdoctoral Trainee, Molecular & Cellular Pathology Jason Craver – Researcher I, Molecular & Cellular Pathology Kiyoung Kim – Postdoctoral Trainee, Molecular & Cellular Pathology

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E D U C AT ION 27th ANNUAL Paulette Shirey Pritchett Endowed Lecture

Elaine Jaffe, M.D., WHO, Delivers Pritchett Lecture Robert Pritchett and family. Dr. Pritchett was a highly respected, young member of the UAB Department of Pathology when she unexpectedly passed away on August 4, 1984. She was a native Alabamian who obtained her medical degree from the University of Alabama, where she was awarded the Stewart Graves Award and the William Boyd Medal for her demonstrated excellence in pathology. L TO R: GEORGE NETTO, M.D., ELAINE JAFFE, M.D., YABING CHEN, PH.D. AND ROBERT PRITCHETT, M.D. “It was a privilege to have Dr. Jaffe deliver the Pritchett lecture UAB Pathology celebrated the 27th this year,” says George Netto, M.D., year of its Paulette Shirey Pritchett Chair, UAB Department of Pathology. Endowed Lecture in Pathology with an “Her talk, on the heels of the publication outstanding lecture by Elaine Jaffe, of the most recent 'blue book' of WHO M.D., Series Editor, World Health classification of tumors, was an enlightOrganization Classification of Tumours. ening update on the latest taxonomy for Jaffe's lecture, “Charting the Future of lymphoma classification.” Lymphoma Classification: A Road Map Jaffe is the author of more than for Disease Discovery and Treatment,” 600 peer reviewed articles, 150 book took place before a full house on chapters and invited reviews, and Monday, September 17, with the Pritchett 38 editorials. She is an editor for the family in attendance. WHO Classification of Tumours of the This endowed lecture series is named Hematopoietic and Lymphoid Tissues. in honor of Dr. Paulette Shirey Pritchett, She completed her medical studies at and is supported by her husband Dr.

Cornell University Medical College and the University of Pennsylvania. She has been Chief of the Hematopathology Section at the NCI since 1980.

Science Watch named

Jaffe among the 10 most highly cited researchers in clinical oncology, and she was included among the 400 most highly cited researchers in Biomedical Science worldwide between 1996 and 2011. Jaffe has held leadership positions in several major medical societies, including the American Society of Hematology, United States and Canadian Academy of Pathology, and the Society for Hematopathology. She has served on 18 journal editorial boards. In 2008, Jaffe was elected to the Institute of Medicine of the National Academies, and in 2013 was awarded the Stratton Medal from the American Society of Hematology. She gave the Henry Rappaport Memorial Lecture at the Lugano International Congress on Malignant Lymphoma in 2013. Jaffe received the 2016 Rous Whipple Award from the American Society of Investigative Pathology.

5th Annual Listinsky Lecture Features World Expert on Glycobiology

THE

UAB Department of Pathology on Tuesday, November 13, welcomed world-renowned expert in glycobiology Richard Cummings, Ph.D., Professor, Harvard Medicine, to present the fifth annual John Jay Listinsky Endowed Lecture in Glycobiology. Cummings, an Alabama native, is Professor of Surgery at Harvard Medical School's Beth Israel Deaconess Medical Center, Director, HMS Center for Glycoscience, and Director, National Center for Functional

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Glycomics. The topic of his lecture was “Integration of Glycomics, Immunology, and Infectious Disease.” Cummings presented his lecture, held in the Comprehensive Cancer Center's Wallace Tumor Institute, to a standing-room only audience. Dr. Jay John Listinsky, an adjunct associate professor of pathology at UAB at the time of his untimely death in 2012, originally trained as a diagnostic radiologist but had a decades-long interest in fucosylated molecules and their overlapping

physiologic properties. He collaborated with investigators in the Division of Anatomic Pathology for many years, which generated a number of novel manuscripts which added important data to the knowledge base of glycobiology. To further this work, his friends, colleagues, and family, spearheaded by his wife and UAB pathologist, Cathy, endowed this lectureship for future generations. The Listinsky lecture is one of several endowed lectureships the Department hosts each year annually.

AWARDS Yemelyanova Named First Hazel Gore Endowed Professor The department is proud to recognize Anna Yemelyanova, M.D., as the inaugural Hazel Gore, M.D., Endowed Professorship in Gynecologic Pathology, generously supported by the Gore family. The University of Alabama Board of Trustees approved the nomination October 1. Yemelyanova joined our team as Professor in the Division of Anatomic Pathology and Director of the Gynecologic Pathology Section in spring of 2018. In addition, Dr. Yemelyanova has the role of Associate Director of our Division of Genomic Diagnostics and Bioinformatics, led by Interim Division Director Shuko Harada, M.D. Yemelanova's previous professional appointments include Associate Professor of Pathology at the Gynecologic Pathology Division at the University of Texas, MD Anderson Cancer Center, and Assistant Professor of Pathology at the Division of Gynecologic Pathology at Johns Hopkins University.

She has formal training in Molecular Genetic Pathology, having received her Doctor of Medicine and completed a residency in internal medicine from Russian State Medical University in Moscow, Russia. Yemelyanova completed her residency at Washington Hospital Center Department of Pathology and Laboratory Medicine, and fellowships at The Department of Pathology, Division of Gynecologic Pathology at Johns Hopkins University School of Medicine and the Division of Molecular Genetic Pathology at the Icahn School of Medicine at Mount Sinai, New York. Her research interests focus primarily on HPV-related lesions of the gynecologic tract; in particular, biomarkers of HPVrelated cancer precursors. She is also conducting research on the development of diagnostic markers of endometrial carcinoma.

diagnoses in gynecologic pathology. She serves as Editorial Board Member for the International Journal of Gynecologic Pathology. Hazel Gore, M.D., a pioneering woman in medicine in Alabama who served on the faculty of the UAB Departments of Pathology and Obstetrics & Gynecology, was among a select few gynecological pathologists from around the world honored in the journal Pathology by Dr. Robert H. Young, Harvard Medical School, for her influence in the development of modern gynecologic pathology.

Yemelyanova is the author of the textbook, Differential Diagnoses in Surgical Pathology: Gynecologic Tract, a guideCYNTHIA MCCALEB GORE (L) AND IRA GORE, M.D., BENEFACline for solving challenging TORS OF THE HAZEL GORE, M.D., ENDOWED PROFESSORSHIP IN GYNECOLOGIC PATHOLOGY, WITH DR. YEMELYANOVA (CENTER).

Chen Wins Best Paper Award Researcher Yabing Chen, Ph.D., won a 2018 “best paper” award from the not-for-profit Science Unbound Foundation. Chen, Professor of Pathology in the UAB School of Medicine and a research career scientist at the Birmingham VA Medical Center, won for

by Jeff Hansen

explaining how dietary potassium regulates calcification of arteries. Chen's winning paper, titled “Dietary potassium regulates vascular calcification and arterial stiffness,” was published in JCI Insight in 2017. The Science Unbound Foundation has as its mission: “Furthering scientific knowledge in the service of health, happiness, and quality of life of humankind

through scientific research and education.” It focuses on research and educational activities in the areas of obesity, nutrition, statistical science and public health. Each year, the foundation offers five awards for best papers published in the preceding year. Winners receive a plaque and a cash prize: $1,000 for faculty and postdocs and $500 for students.

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Pathology Takes Home Three 2018 Argus Awards MEDICAL STUDENTS nominated five Pathology teaching faculty nomi-

Department of Pathology teaching faculty for awards this year, and three of our faculty took home awards. The Argus Awards, created in 1996 to recognize faculty members, give medical students the chance to honor their mentors, professors, courses and course directors for outstanding service to medical education. Faculty are nominated by course evaluations and students vote to select award winners in each category.

Jennifer Gordetsky, M.D., Associate Professor, won for both of her nominations, for Best Educator in the Reproductive Systems Module—her second year in a row winning this category, and Best MS2 Organ Module with co-director Erin Cook, M.D., Obstetrics & Gynecology. This is Gordetsky's third time winning the Best MS2 Organ Module award. The award for Best Educator: Hematology/ Oncology went to Lawrence Williams, M.D., Associate Professor, Anatomic Pathology.

nated for the 2018 Argus Awards, including:

Silvio Litovsky, M.D., Professor, Anatomic Pathology and director of the Cardiovascular Module, was nominated for the Best MS1 Organ System Module and Best Educator in the Cardiovascular Module.

Dr. Jennifer Gordetsky is a five-time Argus Award winner.

Kenneth Fallon, M.D., Associate Professor, Neuropathology, was nominated for Best MS2 Organ Module. Vishnu Reddy, M.D., Professor, Laboratory Medicine, was nominated as Best Educator in the Hematology Oncology Module. “We are so proud to be represented by such stellar teaching faculty in our department,” said George Netto, M.D., Chair of the Department. “A teaching award bestowed by students is a prestigious recognition. Congratuations to each of our nominees and our winners.”

Award nominees and past recipients Drs. Vishnu Reddy (L) and Silvio Litovsky celebrate. Argus photos by Yabing Chen, MD, PhD

Marques & Wende Win Dean's Excellence Award Two of the Department of Pathology faculty members are recipients of the 2018 School of Medicine Dean's Excellence Awards: Marisa Marques, M.D., Professor, Drs. Adam Wende and Marisa Marques, winners of 2018 Dean's Laboratory Excellence Awards Medicine who won the Senior Excellence in Teaching Award, and Adam Wende, Ph.D., Associate Professor in Molecular & Cellular Pathology, with the Junior Excellence in Research Award.

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Fifteen outstanding faculty members were named recipients of the 2018 Dean's Excellence Awards, an honor recognizing exceptional contributions made by School of Medicine faculty in service, teaching, research, diversity enhancement and mentorship.

“I AM SO PLEASED TO ANNOUNCE THE WINNERS

of the 2018 Dean's Excellence Awards,” said Selwyn M. Vickers, M.D., FACS, senior vice president for Medicine and Dean of the UAB School of Medicine. “These awards acknowledge and celebrate the excellent work done by our faculty across these key areas. Each of the individuals honored this year have much to be proud of in their careers here at UAB, and I greatly appreciate what they bring to our community and this institution.” Videos of Drs. Wende and Marques' perspectives on their awards are available at: https://vimeo.com/uabsom.

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Three Faculty Earn Promotions The Department of Pathology is proud to announce the promotion of three of our faculty, effective October 1, 2018.

surgical neuropathology and overseeing and participating in the training of the next generation of pathologists.

James Hackney, M.D. Assistant

Daniel Dye, M.D. Assistant

Professor of Neuropathology and Director of the Pathology Residency Program, receives a promotion to associate professor. Hackney came to academic pathology somewhat late in life, completing a Neuropathology Fellowship at UAB after a 25-year-career spent in the private practice of Surgical Pathology and Hematopathology in New Orleans and Birmingham. Hackney completed his M.D. degree at the University of South Alabama College of Medicine in Mobile in 1979, followed by combined AP/ CP training at Ochsner Clinic in New Orleans, and a Fellowship in Hematopathology at the Hospital of the University of Pennsylvania in Philadelphia. For the last 21 years of his career in private practice, Hackney practiced at St. Vincent's Hospital, Birmingham, serving as Chief of Pathology from 2002 until departing for UAB in 2010 for a two-year Neuropathology Fellowship. His research year was spent in the newly organized Division of Informatics within the Department of Pathology, developing modular, browser-based web apps for diagnostic image analysis in partnership with Division Director Jonas Almeida, Ph.D. Hackney stepped into the role of Program Director of the Pathology Residency Program at UAB in 2016, and now splits time between

Professor of Forensic Pathology, is promoted to associate professor. He joined the department in 2014 and took on the role of Director of the Forensic Pathology Fellowship Program, training and mentoring the next generation of pathologists. He is an integral member of the Jefferson County Coroner's team.

Adam Wende, Ph.D.

Assistant Professor, Molecular & Cellular Pathology, is promoted to associate professor. Wende joined the department in 2012 and has been lauded by such notable distinctions as the School of Medicine's Dean's Excellence Awards this year, with the Junior Excellence in Research Award. “We are proud to announce the well-deserved promotion of these dedicated faculty,” said George Netto, M.D., Chair, Department of Pathology. “Congratulations to each of them for this distinction, marking the next step in their respective academic careers.”

Netto is SOM's 3rd Featured Discovery Recipient Congratulations to our Chairman, George Netto, M.D., on receiving the third UAB School of Medicine Featured Discovery award. This initiative celebrates the important research from UAB School of Medicine faculty members, in particular those published in prominent scientific journals. Netto, an internationally recognized clinician-scientist, was selected for his study titled, “Non-invasive detection of urothelial cancer through the analysis of driver gene mutation and aneuploidy” (eLife, 2018; 7:e32143). Dr. Netto conducted research that found a new test for urothelial cancers, which is less invasive and more accurate. From the announcement by Selwyn Vickers, M.D., FACS, Senior Vice President for Medicine and Dean, UAB School of Medicine: “His study, the 'Non-invasive detection of urothelial cancer through the analysis of driver gene mutation and aneuploidy,' found that the UroSEEK test, which he and colleagues developed, combined with cytology significantly enhanced early detection for patients considered at risk for bladder cancer. The test, which uses urine, significantly reduces the need for invasive testing. This work highlights the remarkable advancements he and other researchers are making to translate scientific findings from the bench to the bedside at rapid speed. I'm honored to work alongside Dr. Netto, who is making tremendous strides in finding more effective and accurate ways to test for urothelial cancers. Netto recorded a UAB MedCast podcast on the topic, entitled, “UroSEEK: A Novel NonInvasive, Urine-Based Test for Urothelial Cancers” that is available on the UAB Medicine website, and offers CME credit.

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Distinguished Faculty Earn Emeritus Status

Two of our distinguished faculty have achieved emeritus status in the Department of Pathology. Congratulations to Dennis Kucik, M.D., Associate Professor, Pathology, and R. Pat Bucy, M.D., Ph.D., Professor, Laboratory Medicine.

Dennis Kucik, M.D., retired on December 31,

2016. Dennis joined UAB's Department of Pathology, Division of Laboratory Medicine in August of 1997. In 2003 he was appointed Chief of Pathology and Laboratory Medicine at the Birmingham Veterans Administration Medical Center. In addition to his invaluable service with the VA, Kucik maintained an active research portfolio during his career. He has been recognized nationally for his achievements related to his NASA-funded research project using both cell and animal models to determine the mechanism of radiation-induced aortic endothelial cell adhesiveness and its consequences for atherosclerosis. His research helped predict the risks associated with interplanetary travel for astronauts, as well as develop countermeasures to mitigate the adverse effects of prolonged exposure to cosmic radiation. Dr. Kucik served as a mentor to many UAB graduate students and Pathology residents throughout the years.

R. Pat Bucy, M.D., Ph.D., retired from active service at UAB on October 1, 2018, and was appointed Professor Emeritus. He joined the Medical Scientist Training Program at Washington University (one of only three in the nation with full funding at the time) in the fall of 1975. Bucy completed his Ph.D. in cellular immunology with a focus on the Ir gene control of immune responses to insulin and graduated in 1981 with both an M.D. and Ph.D. He completed a residency in Anatomic Pathology at Washington University and joined the Faculty there as Assistant Professor in 1984. Bucy joined UAB in 1987. He began his research program focused on T cell biology and clinical service on the autopsy and heart transplant biopsy services. He initiated a long-standing project on murine heart transplant rejection that resulted in characterization of the cytokine expression pattern in murine cardiac allografts and production of multiple transgenic, including the first TCR transgenic mouse line that was specific for an authentic indirect

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alloantigen. Bucy served as the director of the UAB Hospital Flow Cytometry lab in 1989, a role he continued for his remaining tenure at UAB. He initiated a clinical core lab funded by the Adult AIDS Clinical Trial Group in 1996 in collaboration with Dr. Rick Hockett. He was involved in multiple projects in HIV research, including the design and execution of several novel

Dennis Kucik, M.D. (l) with Chair George Netto, M.D.

clinical trials focused on the concept of therapeutic vaccination. He served as the Director of the UAB MSTP program from 2001 to 2006. Bucy was appointed as the Associate Director of the Residency Program for Lab Medicine, and began a focus on teaching critical analysis of medical literature and presentation skills in the Lab Medicine Seminar series. “We are honored to celebrate Dr. Bucy and Dr. Kucik in their respective careers at UAB, each spanning several decades in the laboratory, in research, and teaching,” said George Netto, M.D., Chair, Department of Pathology. “Their legacies run deep in the Department and we are privileged to have had them on our team for so many years. Their contributions will continue to be felt in the years to come. We thank them both for their service to the institution.”

RESEARCH Immune Response Mechanism Described for Fate Determination of T Cells by Jeff Hansen

After a pathogen infects the body, the

immune system responds with a remarkable — and remarkably complicated — cascade of events. Some immune cells, called lymphocytes, migrate to the site of infection; others migrate to areas of the lymph node where antibody production can begin. Profuse signaling among immune cells takes place, through both cell-to-cell contact and release of signaling molecules. The goals of these responses are destruction of the pathogen and repair of tissue injury. During the response, many immune cells undergo maturation into cells with enhanced functions that enable them to respond to particular types of pathogens in specific ways. This is called “effector cell differentiation.”

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For one type of immune cell, called T follicular helper cells, understanding the mechanism of effector cell differentiation could be key to producing better vaccines; helping clinicians fight difficult viral, bacterial or multicellular pathogens; or understanding how to dampen autoimmune diseases.

USING THE REPORTER MICE, they were able to distinguish the IL-2 producers and non-producers and sort them within hours of activation.

In a paper published in the journal Science, University of Alabama at Birmingham researchers and colleagues at four other United States institutions have detailed a mechanism that sets the stage for the fate decision that gives rise to two major subsets of effector cells: T follicular helper cells and non-T follicular helper cells, known as Tfh and non-Tfh cells. Both types of cells develop from naïve T cells that express the surface marker CD4 in the lymph

nodes. When activation signals announce an infection elsewhere in the body, the naïve T cells are induced to develop into Tfh cells or into one of three types of non-Tfh cells — Th1, Th2 or Th17 cells. Tfh cells migrate to the B-cell zones of lymph nodes, where they interact with B cells to CASEY WEAVER, M.D., create germinal centers; there PROFESSOR, UAB PATHOLOGY the B cells produce and release high-affinity antibodies that specifically target the pathogen. Antibody production is one arm of adaptive immunity, and begins only after several days, or sometimes after a delay of weeks. Non-Tfh cells, on the other hand, migrate to the site of entry of a pathogen in non-lymphoid tissues, where they orchestrate the other arm of adaptive immunity — the enhanced function of innate immune cells. During the early events of effector cell differentiation, it was known that a subset of the activated CD4+ T cells started to produce the cell-signaling cytokine interleukin-2, or IL-2. But researchers had no markers to tell which of the activated cells were producing IL-2, nor could they tell which would become Tfh cells and which would become non-Tfh cells. This changed when members of the laboratory of Casey Weaver, M.D., the Wyatt and Susan Haskell Professor of Medical Excellence in Pathology at UAB, genetically engineered IL-2 reporter mice. These mice had a gene for green fluorescent protein linked to the IL-2 gene. As soon as an activated T cell began to produce IL-2, the cell would glow green when exposed to blue light. This allowed automated sorting of IL-2-producing and IL-2-nonproducing cells into two distinct groups. Up until the CONTINUED NEXT PAGE

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development of these reporter mice, the Tfh and non-Tfh cells could be distinguished only two to three days after activation. Using the reporter mice, Daniel DiToro, Ph.D., in the UAB Medical Scientist Training Program, and co-first author, Colleen Winstead, Ph.D., a UAB postdoctoral fellow, were able to distinguish the IL-2 producers and non-producers and sort them within hours of activation. Testing of each group of sorted cells showed that they induced divergent sets of genes. The IL-2-producing T cells induced genes known to be important in Tfh cell development and function. In contrast, the IL-2-non-producing T cells induced genes characteristic of non-Tfh effector cell differentiation. This suggested that IL-2 producers were fated to become Tfh cells, and IL-2 non-producers were fated to become non-Tfh effector cells. This fate determination appeared to be set within hours, even before cell division of the activated T cells had begun. DiToro, Winstead and colleagues in the UAB Department of Pathology; Emory University; HudsonAlpha Institute for Biotechnology, Huntsville, Alabama; Massachusetts General Hospital and Harvard Medical School; and Cincinnati Children’s Hospital used a second reporter mouse engineered in the Weaver lab to prove this fate determination. The second reporter gene, also linked to the IL-2 gene, created a cell surface marker on the IL-2producing T cells. When IL-2-producing cells were selectively removed using an antibody directed against the cell surface marker, no Tfh cells were produced — only non-Tfh cells were left.

The researchers, led by Weaver, also ran a series of experiments to reveal the mechanics that control this early bifurcation of CD4+ T cells into Tfh and non-Tfh effectors. They showed that the percentage of Tfh cells correlated with the amount of antigen used to activate the naïve CD4+ T cells, and the percentage also correlated with the strength with which the antigen bound to antigen receptors of the naïve T cells. IL-2 production was limited to the cells receiving the strongest T-cell receptor signals. “So, it depends on the strength of activation and the strength of signaling,” DiToro said. “Having learned what goes into the development of Tfh cells, we can now manipulate these powerful cells that are required by B cells to drive production of high-affinity antibodies.”

THE RESEARCH TEAM ALSO FOUND that the IL-2 production by cells fated to become Tfh cells acted on the non-IL-2-producing cells through up-regulation of a high-affinity component of the IL-2 receptor, which, in turn, induced genes for differentiation into non-Tfh effector cells. Thus, IL-2 acted in a paracrine manner, meaning it acts in a hormone-like fashion on other cells in the vicinity of cells secreting it. The IL-2 producers were affecting nearby IL-2 non-producers.

One of the genes up-regulated in the IL-2 producing cells was Bcl6, which is important for Tfh cell development. Development of the three types of T helper cells, collectively known as non-Tfh cells, occurs at the same time as Tfh cell development, so the researchers looked at those fate determinations as well. Helper cells are important in adaptive immunity to help suppress or regulate immune responses. The three types respond to three different groups of pathogens — intracellular single-celled protozoal, viral or bacterial pathogens for Th1; multi-celled organisms like worms for Th2; and extra-cellular bacterial or fungal pathogens for Th17. CONTINUED

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Büttner Lecture Integrates Molecular Pathology and Clinical Oncology

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Integrating molecular

diagnostics into patient care to truly personalize medicine is key to the future of successful medicine, in particular cancer care. That was the message delivered by Reinhard Büttner, M.D., Professor and Chair, Pathology, at the University Hospital in Cologne, Germany, when he gave a lecture as part of the joint SurgeryBiomedical EngineeringPathology seminar series, on May 22. Buttner is an authority on the genomics of lung cancer and targeted therapy. Büttner opened his talk with slides showing the

common cranes that twice annually fly over his home in Cologne, Germany, on their migration path south from Scandanavia to Spain and Northern Africa, a journey of some 1,500 miles. He used it as an analogy for pathologists who, in the diagnosing of diseases must also find the right time and mode of treatment, he said. Lung cancer is one of the most frequent causes of cancer deaths worldwide, Büttner said, with high levels in Germany where smoking is still permitted in some public areas and private businesses such as restaurants.

The researchers stimulated naïve CD4+ T cells in conditions designed to drive Th1, Th2 or Th17 development. They found that IL-2 production and Bcl6 mirrored one another under each of these non-Tfh conditions. They then used multiple in vivo inflammatory models to confirm that IL-2 producing cells develop into Tfh, regardless of the inflammatory context. This has led the researchers to a prediction for another subset of T effector cells called memory

Büttner discussed biomarker analysis and histopathology diagnosis in lung cancer, including how to conduct personalized medicine in a large hospital setting. When only 15 to 20 percent of patients are getting resections done, he said, it is a challenge to analyze many genes simulatenously. Büttner is part of a team of world-class researchers making up the Network for Genomic Medicine Lung Cancer, a $12 million-supported national collaborative made up of academic research centers and hospitals throughout Germany. Its stated goal

is to “offer comprehensive and high-quality molecular diagnostics for all patients with lung cancer and thus to promote the implementation of personalized therapy in routine clinical care.” He served as president of the German division of the International Academy of Pathology, and co-president of the joint IAP/ESP Pathology World Congress in 2016. Büttner shared a concluding slide about a patient advocacy group, Bärbel Söhkle, made up of lung cancer survivors who have beaten the odds.

cells. Memory T cells are long-lived cells that previously responded to an infection; they can quickly reproduce after a subsequent infection to produce a faster and stronger immune response. The researchers predict that IL-2 non-producers are fated for effector memory T cells, whereas IL-2 producers are fated for central memory T cells. Central memory T cells are found largely in the lymph nodes; effector memory T cells lack the ability to home to lymph nodes, and they stay in peripheral blood and tissues.

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Possible Treatment

for Rare, Potentially Deadly, Blood-Clotting Disorder by Jeff Hansen

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proof-of-concept experiments, University of Alabama at Birmingham researchers have highlighted a potential therapy for a rare but potentially deadly blood-clotting disorder, TTP. The researchers deliver this therapeutic enzyme via the cellular equivalent of a Trojan Horse, using tiny blood cell platelets as their protective delivery vehicle, with a key enzyme hidden inside. TTP, or thrombotic thrombocytopenic purpura, appears as blood clots in small arterioles throughout the body, particularly in the brain, heart, pancreas and kidneys, resulting in organ damage. The onset of symptoms can be sudden and nonspecific, and the in-hospital death rate remains as high as 20 percent. TTP is caused by lack of the enzyme ADAMTS13 in the blood, most often because of autoantibodies against this enzyme. ADAMTS13 normally acts to cleave a large protein called von Willebrand factor, which is involved in blood clotting. Loss of the enzyme allows destructive microvascular clots to form in important organ tissues. UAB researchers, led by X. Long Zheng, M.D., Ph.D., Robert B. Adams Professor and Division Director of Laboratory Medicine in the Department of Pathology in UAB's School of Medicine, have now reported that platelets can spontaneously take up ADAMTS13. The enzyme stays stable in those cells, and the platelets can effectively deliver the enzyme where it is needed.

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In ex vivo experiments with human blood from TTP patients and in vivo experiments with a mouse model of TTP, the researchers showed that human recombinant ADAMTS13, or rADAMTS13, carried in the platelets can “dramatically” reduce the rate and final amount of blood clot formation in injured arterioles. “Our results for the first time demonstrate that transfusion of rADAMTS13-loaded platelets may be a novel and potentially effective therapeutic approach for arterial thrombosis, associated with congenital and immune-mediated TTP,” Zheng said.

“THIS NOVEL approach could be translated to patient care once rADAMTS13 receives an approval from the U.S. Food and Drug Administration for therapy of congenital TTP.” In previous work published in Blood in 2015, the UAB researchers created transgenic mice, where human rADAMTS13 was expressed exclusively in the platelets. In a background of mice lacking their own ADAMTS13 enzyme, the rADAMTS13-loaded platelets blocked arterial

thrombosis and prevented TTP in the mouse model. As the next step toward patient care, Zheng and colleagues sought to determine whether platelets outside of the body could be loaded with rADAMTS13, such as in blood collected for transfusions. If so, they also wanted to test whether transfusion with those rADAMTS13-loaded platelets could be as effective to block thrombosis and prevent TTP in mice as the transgenic platelets that expressed high levels of rADAMTS13. Four key experiments — described in a study published in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology, or ATVB — answered those questions. First, the researchers incubated isolated human platelets — which are one-fifth the diameter of red blood cells and have a normal function to stop bleeding from blood vessels — for up to two hours in varying concentrations of rADAMTS13 at varying temperatures. At the cold temperature of 4 C, the platelets did not take up rADAMTS13. But at both 25 and 37 C, the platelets took up rADAMTS13, apparently through endocytosis, in a concentration-dependent manner. Second, they showed that the rADAMTS13 taken up by the human platelets remained intact and enzymatically active against von Willebrand factor, a key ingredient for platelet adhesion and aggregation. Also, the rADAMTS13

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was releasable under arterial shear conditions that cause platelet aggregates to break, as simulated with microfluidic channels. Third, using microfluidic channels coated with a fibrillar collagen that simulates the flow in arterioles and presents a surface for clot formation, they showed that addition of rADAMTS13-loaded platelets to normal, TTP-patient and reconstituted-TTP blood dramatically inhibited in vitro thrombus formation under arterial flow. Finally, they showed that transfusion of the rADAMTS13-loaded mouse platelets into genetically engineered mice lacking ADAMTS13 dramatically inhibited thrombus formation in abdominal arterioles after injury.

Thus, it may be possible to pack rADAMTS13 inside human platelets during the time that bags of donated blood sit at room temperature for three days as they are tested for multiple infectious disease markers. These packed platelets could then be transfused into patients with TTP. While routine transfusion of platelets in TTP patients is not recommended, transfusion of rADAMTS13-loaded platelets clearly showed a therapeutic benefit by inhibiting thrombus formation in human and mouse blood lacking ADAMTS13 enzyme. Other researchers have worked on therapeutic strategies to bypass the autoantibody for TTP treatment, with some success. However, unlike Zheng's platelet-ADAMTS13 approach, none of those strategies

have addressed the underlying mechanism of TTP — a lack of ADAMTS13 and/or autoantibody against ADAMTS13. Co-authors with Zheng on the paper, “Transfusion of platelets loaded with recombinant ADAMTS13 is efficacious for inhibiting arterial thrombosis in mice and in human,” are Mohammad S. Abdelgawwad, M.D., graduate student; Wenjing Cao, M.D., Ph.D., instructor of pathology; Liang Zheng, Ph.D., postdoctoral fellow; Nicole K. Kocher, research technician; and Lance A. Williams, M.D., associate professor; all at the UAB Department of Pathology.

Epigenetic Reprogramming of Human Hearts

Found in Congestive Heart Failure by Jeff Hansen

CONGESTIVE HEART FAILURE is a terminal disease that affects nearly 6 million Americans. Yet its management is limited to symptomatic treatments because the causal mechanisms of congestive heart failure — including its most common form, ischemic cardiomyopathy — are not known. Ischemic cardiomyopathy is the result of restricted blood flow in coronary arteries, as occurs during a heart attack, which starves the heart muscle of oxygen. Researchers at the University of Alabama at Birmingham have now described an underlying mechanism that reprograms the hearts of patients with ischemic cardiomyopathy, a process that differs from patients with other forms of heart failure, collectively known as dilated (non-ischemic) cardiomyopathies. This points the way toward future personalized care for ischemic cardiomyopathy.

The study used heart tissue samples collected at UAB during surgeries to implant small mechanical pumps alongside the hearts of patients with end-stage heart failure that assist in the pumping of blood. As a routine part of this procedure, a small piece of heart tissue is excised and ultimately discarded as medical waste. The current study acquired these samples from the left ventricles of five ischemic cardiomyopathy patients and six non-ischemic cardiomyopathy patients, all men between ages 49 and 70. The research team, led by Adam Wende, Ph.D., associate professor in the UAB Department of Pathology, CONTINUED NEXT PAGE

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“ALTOGETHER, WE BELIEVE that epigenetic changes encode a so-called 'metabolic plasticity' in failing hearts, the reversal of which may repair the ischemic and failing heart.”

found that epigenetic changes in ischemic cardiomyopathy hearts likely reprogram the heart's metabolism and alter cellular remodeling in the heart. Epigenetics is a field that describes molecular modifications known to alter the activity of genes without changing their DNA sequence. One well-established epigenetic change is the addition or removal of methyl groups to the cytosine bases of DNA. Generally, hyper-methylation is associated with reduction of gene expression, and conversely, hypo-methylation correlates with increased gene expression.

regulator EZH2. Conversely, the researchers also found hypo-methylation of anaerobic glycolytic metabolic genes. This contribution by EZH2 offers a new molecular target for further mechanistic studies that may aid precision-based heart disease therapies. Of note, co-author Sooryanarayana Varambally, who has spent over 15 years studying this protein, has already made progress using small-molecular inhibitors to regulate EZH2 to treat various cancers.

Wende and colleagues found an epigenetic signature in the heart of patients with ischemic cardiomyopathy that differed from the non-ischemic hearts. Furthermore, this signature was found to reflect a long-known metabolic change in ischemic cardiomyopathy, where the heart's preference of metabolic fuel switches from using oxygen to produce energy in cells, as healthy hearts do, to an anaerobic metabolism that does not need oxygen. This anaerobic metabolic preference is seen in fetal hearts; however, after birth, the baby's heart quickly changes to oxidative metabolism.

The Wende-led study, now published in Nature– Laboratory Investigation, employed a wide array of bioinformatics tools. First author Mark Pepin used publicly available programs to create a fully automated computational pipeline, which is provided as an online supplement to the paper. This protocol, written in the R programming language, allowed the investigators to both analyze their multi-Omics datasets and compare their findings to those of animal-based studies and public data repositories. “Supplying the coding scripts,” Wende said, “is our way of demonstrating the rigor and reproducibility that should be expected of any bioinformatics study.”

“Altogether, we believe that epigenetic changes encode a so-called 'metabolic plasticity' in failing hearts, the reversal of which may repair the ischemic and failing heart.”

Pepin is a sixth-year M.D.-Ph.D. student at UAB and is currently completing the Ph.D. portion of his training in the Medical Scientist Training Program.

The researchers found that increased DNA methylation correlated with reduced expression of genes involved in oxidative metabolism. The transcription factor KLF15 is an upstream regulator of metabolic gene expression, which the researchers found is suppressed by the epigenetic

The UAB team also performed cell culture experiments showing repression of KLF15 after EZH2 over-expression in rat cardiomyoblasts, and they demonstrated that EZH2 over-expression depended on EZH2's having an intact SET catalytic domain.

HEART + SOLE 5K

The Department had a strong showing at this year's Equal Access Birmingham annual event. Held Saturday, August 18, it brought in more than $25,000. Marie-Lise Eich, Pathology Post-Doc, (#9) won the women's overall with a time of 21:45.4. All the UAB Pathology faculty, students and family who participated. L to R: FRONT: Shuko Harada (her first 5K), Frida Rosenblum (with youngest “runner” Ben), Ona Marie Faye-Petersen, Marie-Lisa Eich (women's contestant race winner!), Deniz Peker. BACK: Jennifer Gordetsky, Alexandra (Ali) Simpson, Kerry Nivens (OFP's husband); Daniel Goldberg-Zimrig. NOT PICTURED: Rob Hardy, Maria Del Carmen Rodriguez Pena

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Identifying a Subgroup of Heart Failure Patients

Could Lead to Improved Care by Jeff Hansen

FOR MORE THAN SIX DECADES, oxidative stress has

been linked to heart failure, a progressive weakening of the heart muscle that can lead to death. While antioxidant supplements such as vitamin C, vitamin B and beta-carotene have been widely used in heart failure, they often prove ineffective. Rajasekaran NamakkalSoorappan, Ph.D., of Molecular and Cellular Pathology, School of Medicine at the University of Alabama at Birmingham and colleagues at the PSG-Institute of Medical Sciences & Research, Coimbatore, India, sought to determine whether some heart failure patients might have reductive stress instead of oxidative stress, and whether that condition and its related mechanisms might help personalize treatment of heart failure patients, resulting in better outcomes. Namakkal-Soorappan and colleagues Thiagarajan Sairam, Ph.D., and Ramalingam Sankaran, M.D., recruited patients at PSG Hospitals and found that classifying heart failure patients based on the oxidant vs. antioxidant levels

RAJASEKARAN NAMAKKALSOORAPPAN, PH.D.

in the blood, known as the circulating redox status, may serve as a predictive tool for guiding personalized antioxidant therapies. Specifically, they found that members of a subgroup of heart failure patients have a hyper-reductive state, called reductive stress, and some have normal redox states. This raises some interesting questions about one of the most prevalent health issues facing Americans today.

“We are hypothesizing

that the general treatment of antioxidants for heart failure may not be beneficial for a subset of heart failure patients,” NamakkalSoorappan said. “Patients with normal redox may not need any antioxidants. There is very solid evidence that antioxidants seem to fail in some patients, possibly because the right antioxidant was not used. The specificity of antioxidants is very important for its use.” The study, “Evidence for a hyper-reductive redox in a sub-set of heart failure patients,” was published in the Journal of Translational Medicine on May 18. While sample size was relatively small — 54 heart failure patients and 42 healthy controls — the results could impact how heart failure patients are treated and could guide personalized antioxidant therapies. “This was the first evidence to correlate some heart patients' having too many antioxidants,” Namakkal-Soorappan said. The study used the circulatory redox state to separate the heart

failure patients into normal redox, hyper-oxidative and hyper-reductive groups. A majority of patients, 42 percent, exhibited a hyper-oxidative state; nearly an equal number, 41 percent, exhibited a normal redox state; and 17 percent exhibited a hyper-reductive state. “This finding suggests a strong implication for reductive stress in the progression of heart failure, but the mechanisms are unknown,” Namakkal-Soorappan said. Namakkal-Soorappan, along with Ivor Benjamin, M.D., and their research team at the University of Utah Department of Medicine, first discovered in 2007 that hypertrophy, or enlargement of the heart, is caused by a chaperone protein, alpha-B-crystallin, that is mutated in cardiac myocytes, the muscle cells of the heart associated with reductive stress. “The cardiac cells respond to stress by enlarging,” NamakkalSoorappan said. “Patients who have this genetic mutation develop hypertrophy.” This enlargement normally occurs when patients are in their 40s or older, as aging usually leads to oxidative stress. “However, when we closely studied this mutated gene in animal models over their lifespans, transgenic mice developed hypertrophy in six to eight months, which is equivalent to a human being in his or her late 30s, and to our surprise, these mice had excess levels of antioxidants to create reductive stress,” he said. “We thought it could be oxidative CONTINUED NEXT PAGE

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R E S EAR C H because of aging, but it's not.” We decided to use the terminology of reductive stress — originally named in the 1960s and lately as seen in patients with Alzheimer's disease, but not often described in pathophysiology of other major human diseases.”

What does this mean clinically?

Though the sample size is not sufficient to make definitive conclusions, it simply means that patients come in diverse forms, though their clinical diagnosis may be the same, and therefore

in terms of treatment “one size does not fit all.” Prescribing antioxidant treatment to all may not only not be beneficial, but could result in harm. The good news is that testing for reductive stress is accomplished easily in about two hours with a blood test, says co-senior author Ramalingam Sankaran, dean and professor at the PSG Institute of Medical Sciences & Research, Coimbatore, Tamil Nadu, India. Future steps include a study to screen for reductive stress in several different heart diseases that lead to heart failure, with

a long-term goal of conducting collaborative research as part of a multi-site clinical trial, NamakkalSoorappan says. “We would like to study a couple thousand patients and screen them for genetic mutations, and analyze for correlations to study how human beings develop this reductive stress,” Thiagarajan and Namakkal-Soorappan said.

Immune Cells Identified

that Create and Sustain Chronic IBD by Jeff Hansen

IN PRECLINICAL EXPERIMENTS,

Laurie Harrington, Ph.D., and colleagues at the University of Alabama at Birmingham have discovered a subset of immune cells that create and sustain chronic inflammatory bowel disease. These cells could become potential therapeutic targets to ameliorate or cure Crohn's disease and ulcerative colitis.

Inflammatory bowel disease, or IBD, has two forms: Crohn's disease, which can affect any part of the gastrointestinal tract but most often occurs in the lower small intestine; and ulcerative colitis, found in the large intestine and rectum. In both, prolonged inflammation damages the GI tract, accompanied by symptoms that include persistent diarrhea and abdominal pain.

Furthermore, if this subset of CD4 T cells plays a similar role in other autoimmune diseases, such as Type 1 diabetes, multiple sclerosis or rheumatoid arthritis, they could also be targets for therapy.

IBD is an autoimmune disease caused by a dysfunctional immune response, yet the mechanisms of how the immune cells cause chronic inflammation and pathology are unknown. In IBD, the cytokine interferon-gamma is abundantly produced by a type of immune cells called CD4 T cells, yet there is conflicting information about the role of interferon-gamma in the disease.

VICTOR M. DARLEY USMAR, PH.D., PROFESSOR, UAB PATHOLOGY, CO-AUTHOR OF THE STUDY.

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“We think these cells could be in a number of auto-inflammatory diseases,” said Harrington, an associate professor in the UAB Department of Cell, Developmental and Integrative Biology. “Our hope is, if we could treat these cells, it could be curative.”

The immune system in mammals functions via an exquisite series of interactions among a large cast of different immune cells. The goal is to trigger a response that will identify and eliminate infecting bacteria or viruses, and then turn off that response when the infection is gone. At the same time, the immune response is not supposed to attack a person's own cells, a harmful attack that is called autoimmunity.

RE SE AR C H This tightly controlled immunity starts with blood-line stem cells in the bone marrow that have the capacity to differentiate into a large number of different immune cells. The stem cells themselves can divide indefinitely. The stem cells produce intermediate cells known as progenitor cells. Progenitor cells can divide for a while, but not indefinitely, and they have the ability to further differentiate into one or several types of fully differentiated immune cells. As an example, effector CD4 T cells are progenitors that can differentiate into various types of T-helper cells that are found in IBD. In a mouse model of colitis, Harrington, first author Boyoung Shin and colleagues found that effector CD4

Inflammatory bowel disease has 2 forms: Crohn's disease, which can affect any part of the gastrointestinal tract but most often occurs in the lower small intestine; and ulcerative colitis, found in the large intestine and rectum. T cells exist in a spectrum of differentiation states, and the pathogenic potential of the cells was directly linked to the differentiation status. They were able to separate the CD4 T cells into two groups: interferon-gamma-producing CD4 T cells and CD4 T cells that did not produce interferon-gamma.

The interferon-gamma-positive CD4 T cells were not able to confer colitis when transferred to healthy mice, and those cells were not required to sustain disease. In contrast, it was the interferon-gamma-negative CD4 T cells that were pathogenic. Those cells were capable of eliciting and maintaining intestinal inflammation. That group showed a stem cell-like transcriptional signature, which supports the capacity to self-renew and resist the programmed cell death, called apoptosis. They also continually seeded terminally differentiated, interferon-gamma-producing cells in the inflamed intestine. The researchers also identified a glycosyltransferase enzyme in the interferon-gamma-negative CD4 T cells that positively regulated a transcription factor involved in stemness. Similar to the Harrington study, a different group of researchers recently found there is a distinct subset of CD8 T cells that sustains the control of chronic viral infections, and this unique cell population is distinguished by its stem-like qualities. Besides Harrington and Shin, co-authors of the study, “Effector CD4 T cells with progenitor potential mediate chronic intestinal inflammation,� published in the Journal of Experimental Medicine, are Robert L. Kress and Susan L. Bellis, UAB Department of Cell, Developmental and Integrative Biology; and Philip A. Kramer and Victor M. Darley Usmar, UAB Department of Pathology. This work was supported by National Institutes of Health grants DK084082, AI113007, GM111093 and DK079337; American Heart Association grant 16PRE29650004; a UAB Multiple Sclerosis Center grant; and a UAB School of Medicine Blue Sky Award. At UAB, Darley-Usmar holds the Endowed Professorship in Mitochondrial Medicine and Pathology.

L TO R FRONT: JAROSLAW ZMIJEWSKI, PH.D.; KAREN BERNARD, PH.D.; ANNA ZMIJEWSKA, PH.D; AND VICTOR DARLEY-USMAR, PH.D.; BACK: NATHANIEL BONE, PH.D.; ROSLYN MANNON, M.D.; MORGAN LOCY; AND VICTOR THANNICKAL, M.D. 2019 Vol. 1, Issue 1 | UAB Pathology

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Scientists Reverse Aging-associated Skin Wrinkles and Hair Loss in a Mouse Model by Jeff Hansen

Wrinkled skin and hair loss are hallmarks of aging. What if they could be reversed? Keshav Singh, Ph.D., and colleagues have done just that, in a mouse model developed at the University of Alabama at Birmingham. When a mutation leading to mitochondrial dysfunction is induced, the mouse develops wrinkled skin and extensive, visible hair loss in a matter of weeks. When the mitochondrial function is restored by turning off the gene responsible for mitochondrial dysfunction, the mouse returns to smooth skin and thick fur, indistinguishable from a healthy mouse of the same age. “To our knowledge, this observation is unprecedented,” said Singh, a professor of pathology and genetics in the UAB School of Medicine. Importantly, the mutation that does this is in a nuclear gene affecting mitochondrial function, the tiny organelles known as the powerhouses of the cells. Numerous mitochondria in cells produce 90 percent of the chemical energy cells need to survive. In humans, a decline in mitochondrial function is seen during aging, and mitochondrial dysfunction can drive age-related diseases. A depletion of the DNA in mitochondria is also implicated in human mitochondrial diseases, cardiovascular disease, diabetes, age-associated neurological disorders and cancer. “This mouse model,” Singh said, “should provide an unprecedented opportunity for the development of preventive and therapeutic drug development strategies to augment the mitochondrial functions for the treatment of aging-associated skin and hair pathology and other human diseases in which mitochondrial dysfunction plays a significant role.”

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The mutation in the mouse model is induced when the antibiotic doxycycline is added to the food or drinking water. This causes depletion of mitochondrial DNA because the enzyme KESHAV SINGH, PH.D. to replicate the DNA becomes inactive. In four weeks, the mice showed gray hair, reduced hair density, hair loss, slowed movements and lethargy, changes that are reminiscent of natural aging. Wrinkled skin was seen four to eight weeks after induction of the mutation, and females had more severe skin wrinkles than males. Dramatically, this hair loss and wrinkled skin could be reversed by turning off the mutation. The photos below show the hair loss and wrinkled skin after two months of doxycycline induction, and the same mouse a month later after doxycycline was stopped, allowing restoration of the depleted mitochondrial DNA. Little change was seen in other organs when the mutation was induced, suggesting an important role for mitochondria in skin compared to other tissues.

The wrinkled skin showed changes

similar to those seen in both intrinsic and extrinsic aging — intrinsic aging is the natural process of aging, and extrinsic aging is the effect of external factors that influence aging, such as skin wrinkles that develop from excess sun or long-term smoking. Among the details, the skin of induced-mutation mice showed increased numbers of skin cells, abnormal thickening of the outer layer, dysfunctional hair follicles and increased inflammation that appeared to contribute to skin pathology. These are similar to extrinsic aging of the skin in humans. The mice with depleted mitochondrial DNA also showed changed expression of four

RE SE AR C H

Magnanimous Gift from Former Pathology Chair aging-associated markers in cells, similar to intrinsic aging. The skin also showed disruption in the balance between matrix metalloproteinase enzymes and their tissue-specific inhibitor — a balance of these two is necessary to maintain the collagen fibers in the skin that prevent wrinkling. The mitochondria of induced-mutation mice had reduced mitochondrial DNA content, altered mitochondrial gene expression, and instability of the large complexes in mitochondria that are involved in oxidative phosphorylation. Reversal of the mutation restored mitochondrial function, as well as the skin and hair pathology. This showed that mitochondria are reversible regulators of skin aging and loss of hair, an observation that Singh calls “surprising.”

“It suggests that epigenetic mechanisms underlying mitochondria-to-nucleus cross-talk must play an important role in the restoration of normal skin and hair phenotype,” Singh said, who has a secondary UAB appointment as professor of pathology. “Further experiments are required to determine whether phenotypic changes in other organs can also be reversed to wildtype level by restoration of mitochondrial DNA.” Co-authors with Singh for the paper, “Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function,” published in the Cell Death and Disease, a Nature online journal, are Bhupendra Singh, Trenton R. Schoeb and Prachi Bajpai, UAB Department of Genetics; and Andrzej Slominski, UAB Department of Dermatology. This work was supported by Veterans Administration grant 1I01BX001716 and National Institutes of Health grants CA204430, AR071189-01A1 and AR073004. At UAB, Singh holds the Joy and Bill Harbert Endowed Chair in Cancer Genetics, and Slominski holds the Endowed Professorship in Basic Research in the Department of Dermatology.

Jay McDonald, M.D.,

Professor Emeritus and former chair of the Department of Pathology, is a champion of the department who, with his wife Sarah, continue to generously support its mission. In 2010, Dr. and Mrs. McDonald established the Jay M. McDonald Endowed Professorship in Bone Pathobiology. Five years later, the McDonalds generously funded the Jay M. McDonald Endowed Professorship in Laboratory Medicine. In late 2018, the McDonalds pledged continued support of the endowments.

JAY MCDONALD, M.D.

McDonald’s academic career spanned three decades and included Directorship of the Division of Laboratory Medicine in the Departments of Pathology and Medicine at Washington University School of Medicine in St. Louis for 10 years prior to his recruitment to UAB in 1990 to Chair the Department. He served as Chair of UAB Pathology from 1990–2008, and was Editor-in-Chief of the primary pathology research journal, The American Journal of Pathology, from 2003–2008. He directed an NIH-funded Center for Metabolic Bone Disease — one of five in the country — from 1996–2010. “Dr. McDonald’s continued commitment to the UAB Department of Pathology illustrates his dedication to and passion for the field,” says George Netto, M.D., Chair. “In his tenure as chair, McDonald grew the department into prominence nationally, increasing faculty and research funding to make it one of the country’s top-ranked programs. The impact of his ongoing role supporting excellence in research and teaching through these endowments continues to be felt deeply by the next generation of UAB pathologists.”

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Croatian Pathology Faculty Visit Department in Research Exchange he said. “Apart from great infrastructure and strong management, it was highly motivating to meet great people 'creating' UAB by their honest commitment to clinical practice, teaching and research. It was inspiring!” During the visit, Netto gave his first Grand Rounds presentation to the department since arriving at UAB, on the topic of “Changing the Landscape of Bladder Cancer Management,” which the visiting group attended. “We are excited about the opportunity for the exchange of ideas, future collaborations in research, training and education with a premier university such as the University of Zagreb,” Netto said. “This visit is just one in a series of what we hope will be a long-lasting relationship with our European counterparts. We stand to learn a great deal from one another.” DRS. VARAMBALLY (L), NETTO (CENTER) AND PONNAZHAGAN (R) ENJOY THE COMPANY OF CROATIAN COLLEAGUES DURING THEIR VISIT.

The Department of Pathology was proud to wel-

come visiting faculty from the University of Zagreb and the University Clinical Hospital in Zagreb, Croatia, in April. The visit was part of a reciprocal exchange initiated by Department Chair Dr. George Netto, who visited the university in Eastern Europe in winter 2017. The visitors included Monika Ulamec, M.D., Ph.D., Assistant Professor of Pathology, Clinical Department of Pathology & Cytology at the University Clinical Hospital; Ana Katusic Bojanac, Ph.D., and Nino Sincic, M.D., Ph.D., both asssisant professors in the Department of Biology, School of Medicine, University of Zagreb. The trio spent three days in Birmingham visiting with faculty in the Department of Pathology as well as in the School of Health Professions. They also visited several pathology labs around campus, and said they were impressed with what they saw. “This visit was very pleasant and useful as we got the opportunity to meet with wonderful people who work at your Hospital and University,” Ulamec said. “You have a great network of basic researchers and clinicians collaborating and working together. I'm sure this is just the beginning of collaboration between our institutions.” Dr. Sincic agreed. “I must confess that we expected a lot from our visit to UAB and I'm glad to say that we found even more,”

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In 2017, UAB signed a memorandum of understanding with the University of Zagreb School of Medicine, represented by the dean, Professor Marijan Klarica, M.D., Ph.D., and the UAB Board of Trustees, represented by Senior Vice Provost and Senior International Officer, Suzanne Austin, Ph.D., with the intent of establishing “joint relations and working schemes on projects of mutual academic interests, both for the advancement of knowledge in their particular field of inquiry, as well as for the development of good relations between their respective institutions and cultural environments.” UNIVERSITY OF ZAGREB FACULTY WELCOME DR. GEORGE NETTO TO CROATIA.

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Inaugural Pilot Awards

Support Translational and Clinical Research This spring the Department launched its inaugural Pilot Grant Awards Program to support clinical and translational research. The program, spearheaded by Rakesh Patel, Ph.D., Professor, Molecular & Cellular Pathology, was inspired in part by feedback provided at an annual department-wide faculty retreat. The request for proposals was announced in December 2017, with a proposal deadine of February 15, 2018, and requests for full applications announced on March 15. The Translational Research Pilot Awards encouraged multi-PI projects that have advanced beyond the first stages of planning, designed to generate sufficient data for use in extramural funding applications including large programmatic grants (e.g., R01, DoD, PPG, P50, U54). Projects that are responsive to upcoming/issued RFAs were highly encouraged.

2

Translational Research Pilot Awards were chosen from 10

applications, and funded at the rate of $25,000 each for one year starting June 1. They are:

“Nuclear-mitochondrial Genetic Interaction Drives Tumor Metabolism and Breast Cancer Growth,” with principle investigators Douglas Hurst, Ph.D., Assistant Professor, Molecular & Cellular Pathology and Scott Ballinger, Ph.D., Professor, Molecular & Cellular Pathology

1

2

“Novel Transcriptional Regulation of Lysosomal Biogenesis and Autophagy

in Cardiac Pathophysiology,” with principle investigators John Chatham, Ph.D., Professor, Molecular & Cellular Pathology and Jianhua Zhang, Ph.D., Associate Professor, Molecular & Cellular Pathology Awardees provide a six-month interim progress report detailing accomplishments and future plans and will be required to present their findings at the Department of Pathology Grand Rounds. Clinical Research Pilot Awards are designed to provide seed support to facilitate and enhance Translational Research programs and scholarly activity across the Department. Projects in the early stages of planning that will advance our academic, scholarly and research missions were especially welcome. Examples of anticipated use of funds included: supporting collection of data to be used in conference presentations, peer-reviewed publications and extramural grant applications.

6

Clinical Research Awards

were funded at the rate of $5,000 each for one year starting June 1. They are:

“Autophagy-related Gene GABARAPL1 in Linking Obesity and Breast Cancer Disparity,” Shuko Harada, M.D., Associate Professor of Pathology, Head of Molecular Diagnostic Laboratory, Interim Division Director, Genomics and Bioinformatics

1

“Idenification of Genetic Determinants of Diffuse Cirrhosis-Like Hepatocellular Carcinoma,” Sameer Al Diffalha, M.D., Assistant Professor of

2

Pathology, GI Fellowship Director, Division of Anatomic Pathology “Histological and Molecular Biomarkers for Risk-Stratyfying Colorectal Cancer,” Rong Jun Guo, Ph.D., Assistant Professor of Pathology, Division of Anatomic Pathology

3

“Circulating Biomarkers in Acquired Thrombotic Thrombocytopenic Purpura: Roles of Neutrophil Activation and Systemic Inflammation,” Wenjing Cao, M.D., Ph.D., Instructor, Department of Pathology, Division of Laboratory Medicine

SAMEER AL DIFFALHA, M.D.

4

“Development of a Circulating Debulking Signature to Predict Optimal Versus Suboptimal Cytoreduction of Ovarian Cancer,” Liyun Cao, M.D., Instructor, Department of Pathology, Division of Laboratory Medicine

RAKESH PATEL, PH.D.

5

“Discordance Between the Partial Thromboplastin Time (PTT) and the anti-Xa While Monitoring Heparin Therapy: A Pilot Study For Discovery of Clinical Significance and Underlying Mechanisms,” Lawrence Williams, M.D., Associate Professor of Pathology, Director of Therapeutic Apheresis, Division of Laboratory Medicine

SCOTT BALLINGER, PH.D.

6

“The Department is encouraged by the response we received from this initial RFA, and we look forward to fostering the research of these innovative investigators throughout the year,” Patel said. “We are excited at how this work enhances the Department's research portfolio, and look forward to seeing where it leads.”

LAWRENCE WILLIAMS, M.D.

SHUKO HARADA, M.D.

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Big Change from a Small Player

Mitochondrial background modulates whole body metabolism and gene expression

A

by Jeff Hansen About 1.5 billion years ago, tiny visitors came to live inside the cells that later evolved into all plant and animal life — including humans. Those visitors were mitochondria, small organelles whose prominent role is producing 90 percent of the chemical energy cells need to survive. Evolutionarily speaking, humans, animals and plants are thus a combination of two organisms. Mitochondria have their own DNA, but the 13 genes in human mitochondria — along with DNA sequences for tRNAs, rRNAs and some small peptides — are massively overshadowed by the 20,000 genes in the human nucleus. Nevertheless, these diminutive mitochondria may have a strong influence on cellular metabolism and susceptibility to metabolic diseases like heart failure or obesity, according to preliminary research by Scott Ballinger, Ph.D., UAB Professor of Pathology.

SCOTT BALLINGER, PH.D.

“For 50 years, researchers have tried to find disease susceptibility using Mendelian genetics,” Ballinger said, speaking about studies of the chromosomal genes in the cell nucleus. “But this explains only 10 percent of the reasons for susceptibility to disease.”

The possible impact of mitochondrial DNA on disease susceptibility depends on two facts. First, all of a person's mitochondrial DNA comes from the mother, via her egg. This is distinct from the chromosomal genes in the nucleus, where, on average, half come from the mother and half from the father. Second, human mitochondrial DNA has evolved into distinct haplotypes, and each of these types has mitochondrial DNA variations that are inherited together. There are approximately 25 to 35 basic mitochondrial DNA haplogroups, and one of them — found in African populations — has many subtypes due the deep genetic diversity of that continent. TO INVESTIGATE THE IMPACT of mitochondrial DNA, Ballinger and colleagues looked for changes in metabolism and nuclear gene expression when they exchanged mitochondrial backgrounds of strains of mice — specifically those having different mitochondrial DNA sequences, and also having notable differences in susceptibility to diseases associated with metabolism. After switching the mitochondrial DNA backgrounds, Ballinger and colleagues measured changes in body composition,

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metabolism and nuclear gene expression in fat tissue when mice switched from a low-fat chow diet to a high-fat diet.

“

In the first report of its kind, they found that switching the mitochondrial genetic background had a significant impact on adiposity, whole body metabolism and nuclear gene expression in mice.

The overall implication of this work is that it can provide a new framework for understanding complex genetic disease susceptibility.

For example, gene expression in both visceral and subcutaneous fat was markedly changed between mice sharing the same nuclear genome but having different mitochondrial DNA backgrounds, when fed chow versus a high-fat diet. These changes ranged from 10- to 50-fold differences in the number of genes affected, and mitochondrial DNA background influenced whether the number of affected genes were increased or decreased. These studies also found that metabolic efficiency and percentage of body fat in the mice were impacted as well. “These results are clearly consistent with the notion that different nuclear-mitochondrial genetic combinations influence metabolism, adiposity and gene expression in different ways,” Ballinger said. “The overall implication of this work is that it can provide a new framework for understanding complex genetic disease susceptibility — that both an individual's nuclear and mitochondrial genomes, in combination, can affect disease development. We are now trying to understand how the different combinations of nuclear and mitochondrial encoded genes interact to alter metabolism, and how this influences individual disease susceptibility.” Co-authors with Ballinger of the paper, “Mitochondrialnuclear genetic interaction modulates whole body metabolism, adiposity and gene expression in vivo,” published in the journal EBioMedicine, are Kimberly Dunham-Snary, Melissa Sammy, David Westbrook and Ryan McMonigle, Division of Molecular and Cellular Pathology, UAB Department of Pathology; Michael Sandel, Department of Biostatistics, UAB School of Public Health; Rui Xiao and Arthur Penn, Louisiana State University School of Veterinary Medicine; and William Ratcliffe and Martin Young, UAB Department of Medicine.

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UALCAN: A Tool

for Interpreting & Presenting the Growing Pool of Cancer Data Recent advances in sequencing technology have led to a tremendous surge in generation genomics and transcriptomics data. The Cancer Genome Atlas (TCGA) consortium, a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) — both part of the NIH — has utilized such modern technologies to sequence samples from thousands of cancer patients, over a wide variety of cancers. Big data analysis from the project has led to the comprehensive molecular characterization of multiple cancer types and the identification of potential biomarkers. Such high volume of data present an excellent opportunity for cancer researchers and clinicians to raise questions associated with tumor heterogeneity and racial disparity, and to unearth novel cancer-subtype–specific markers. Systematic cancer data exploration by cancer researchers and clinicians requires analysis platforms with user-friendly features. While there are computational tools available to aid researchers in carrying out specific TCGA data analyses, a need arose for a resource to facilitate the analysis of gene expression and survival profiles for tumor subgroups and molecular subtypes of cancers.

TO ADDRESS THIS ISSUE, a group of researchers in the

Department of Pathology led by Sooryanarayana Varambally, Ph.D., Associate Professor, Molecular and Cellular Pathology and Director, Translational Oncologic Pathology Research, O'Neal Cancer Center with Darshan Chandrashekar, Ph.D., Postdoctoral Fellow, developed the University of ALabama CANcer Database, or UALCAN, an easy-touse, interactive web portal to perform in-depth analyses of TCGA gene expression data.

UALCAN uses TCGA RNAsequencing and patients' clinical data from 33 different cancer types, paired with sequencing data from metastatic breast and prostate cancer data from the University of Michigan. The web-based platform's user-friendly features facilitate: expression analysis of a query 1 Relative gene(s) across tumor and normal

samples, as well as in various tumor sub-groups based on individual cancer stages, tumor grade, race, body weight or other clinico-pathologic features Understanding 2 impact of gene

the combined expression level and clinico-pathologic features on patient survival of the top over- and 3 Identification under-expressed genes in individual cancer types

analysis of pre-compiled 4 Pan-cancer gene classes or user-defined gene list ability to list co-expressed 5 The genes and explore promoter DNA

methylation status in specific cancers

This resource aids in in silico (computer-simulated) validation of target genes and in identifying tumor subgroup–specific candidate biomarkers. UALCAN allows users to export results of gene expression and survival analysis as publication-ready graphic images in png, jpeg, and PDF formats. The pre-derived list of the top 250 over-/ under-expressed genes for major cancers (with large sample size), as well as popular cancer subtypes (e.g. triple negative breast cancer [TNBC]; prostate tumors with ETS-fusion) is provided via a heatmap feature. This serves as a ready-to-use list of potential markers for further exploration. UALCAN serves as a one-stopshop, providing easy access to external resources such as GeneCards, Human

Protein Reference Database (HPRD) (to explore relevant protein interactions),PubMed, TargetScan (to find predicted microRNA that potentially regulate the gene of interest) and the Human Protein Atlas (to investigate protein expression in various cancers). Since its release to the public in 2017, UALCAN has been visited more than 110,000 times by users from over 80 countries, and is frequently cited. “We believe that UALCAN will be extremely helpful in accelerating cancer biomarker and therapeutic target identification,” says Varambally. “In the near future we will add new functionality to UALCAN, including non-coding RNA and microRNA expression analyses.”

USERS AGREE. “[I'm ] currently driving through UALCAN and I am liking it…finding UALCAN very user friendly,” says Craig Southern, Ph.D., Senior Scientist, Center for Therapeutic Discovery, LifeArc, in London. X. Shirley Liu, Ph.D., in the Department of Biostatistics and Computational Biology at Dana-Farber Cancer Institute and Harvard Medical School says, “I played around with UALCAN, and it is a really nice tool.” UALCAN is supported by UAB Pathology, the O'Neal Comprehensive Cancer Center, UAB School of Medicine and the Breast Cancer Research Foundation of Alabama (BCRFA). Dr. Chandraskehar presented a lecture on UALCAN at this year's UAB O'Neal Cancer Center Retreat, held November 18. Dr. Varambally has given numerous talks about the tool at conferences worldwide. UALCAN is publicly available at: http://ualcan.path.uab.edu or by searching Google for “UALCAN”. The tool's Twitter account is @Now_UALCAN. 2019 Vol. 1, Issue 1 | UAB Pathology

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3RD ANNUAL

TTP Fair Showcases Research Progress For the past two years, the research lab of X. Long Zheng, M.D., Ph.D., Division Director, Laboratory Medicine, UAB Department of Pathology, has hosted an annual THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) FAIR AND EDUCATION DAY. The event unites physicians and researchers working to improve the available treatments, outcomes, and recovery times for the disease, with patients and community members affected by TTP.

postdoctoral fellow in Long Zheng's lab, was recently given a fellowship award by the American Heart Association to continue his work on “A Novel Zebrafish Model of Thrombotic Thrombocytopenic Purpura (TTP).” Funding started in July and continues for one year, with the opportunity for renewal for a second year.

TTP is a rare blood disorder in which blood clots form in small blood vessels throughout the body. The clots can limit or block the flow of oxygen-rich blood to the body's organs, such as the brain, kidneys, and heart. As a result, serious health problems can develop.

Mohammad Abdelgawwad, M.D. graduate student studying pathogenesis and molecular medicine in the Zheng lab, received a year-long Ireland Travel Research Scholarship from the UAB Graduate School to travel to the University of Pennsylvania. There he will study the use of platelet-delivered ADAMTS13 as a novel therapeutic approach for acquired TTP.

This year's TTP Fair and Education Day took place Saturday, June 9, in the Shelby Biomedical Research Building.

“We are using platelets as targeted drug delivery especially in TTP patients since they have very low platelet count,” Abdelgawwad says. “We use platelets as a Trojan horse to hide ADAMTS13 from being recognized by its autoantibodies so it would cleave VWF.”

Purpura” was featured in Haematologica, the journal of the European Haematology Association, online on August 23, 2018. Elizabeth Staley, M.D., Ph.D., Hemostasis Fellow of Pathology, was first author on the paper, along with colleagues Wenjing Cao, M.D., Ph.D., Instructor, Pathology; Nicole Kocher, Researcher, TTP Lab; Lucy Zheng, senior of Indian Springs School, Huy Pham, M.D., M.P.H., and Robin Lorenz, M.D., Ph.D., former Assistant Professor and Professor of Pathology, respectively, Lance Williams, M.D., Associate Professor of Pathology, Marisa Marques, Ph.D., Professor, and X. Long Zheng, M.D., Ph.D., Professor of Pathology and Division Director, Laboratory Medicine.

THE SECOND, “Transfusion of

“The Zheng Lab has made many major contributions to the understanding of the structure-function relationship and regulation of ADAMTS13,” Zheng says. “We are working to develop novel tools for the diagnosis and treatment of TTP.”

Also, two papers featuring the results of research conducted in the laboratory of X. Long Zheng, M.D., Ph.D., related to the pathogenesis and novel therapeutics for immune-mediated thrombotic thrombocytopenic purpura (iTTP) were published recently.

platelets loaded with recombinant ADAMTS13 is efficacious for inhibiting arterial thrombosis in mice and in human,” was published with first author Abdelgawwad in the journal Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), on September 13, 2018. Other contributors include Wenjing Cao, M.D., Ph.D., Nicole Kocher, B.S., Lance Williams, M.D., Liang Zheng, and X. Long Zheng. The findings suggest that transfusion of recombinant ADAMTS13-loaded platelets may be a novel and potentially effective therapeutic approach for arterial thrombosis, including congenital and immune-mediated thrombotic thrombocytopenic purpura.

Two of Zheng's are studying TTP awarded funds to research. Liang

The first, “Clinical Factors and Biomarkers Predicting Outcome in Patients with Immune-Mediated Thrombotic Thrombocytopenic

Haematologica and ATVB are top journals in the field of Hematology, with an impact factor of 9.09 and 6.6, respectively.

THE ZHENG LAB is interested

in understanding the biological mechanism of TTP, which is caused by a deficiency of active ADAMTS13, the enzyme responsible for cleaving Von Willebrand Factor (VWF), a large protein involved in blood clotting. Zheng was among the first group of investigators who discovered and cloned the ADAMTS13 enzyme.

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students who were recently advance their Zheng, Ph.D.,

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For more information and online registration for the TTP fair, visit: TTPResearchGroup.Path.UAB.edu.

AND MO R E A Fond Farewell to

Dr. Robin Lorenz

It was a bittersweet gathering as the Department came together on June 26 to celebrate the contributions of Robin Lorenz, M.D., Ph.D., to the Department and the University. Lorenz was Professor, Department of Pathology and Medical Education; Associate Dean for Physician Scientist Development; Director, UAB Medical Scientist (MD-PhD) Training Program; Director, UAB Medical Student Summer Research Program (MSSRP), and many other key roles. She accepted a position with Genentech as senior director of pathology. At UAB, she held secondary faculty appointments in the UAB departments of Medical Education and Microbiology, and was a member of the O'Neal Comprehensive Cancer Center, the Comprehesive Diabetes Center, and the Comprehensive Arthritis, MSK, Bone & Autoimmunity Center. Lorenz joined UAB in 2002 as Associate Professor of Pathology. In 2006, she took over the UAB Medical Scientist (M.D.-Ph.D.) Training Program (MSTP). In 2015, Lorenz helped establish the UAB Physician Science Development office for which she served as Associate Dean. Lorenz was recently featured on an extended podcast by MagicCity Medcast, a series produced by UAB School of Medicine medical students. In it, she describes how she grew up on a cattle farm outside of tiny O'Keene, Oklahoma, also known as the “rattlesnake capital of the world.” She says, “I think one of the things that has made me successful in science to this day is the work ethic that really gets instilled in you in growing up on a farm.” She originally thought she wanted to be a veterinarian. Lorenz says she got interested in science because of her father, who had a career running hospital labs, and first taught her how to pipette and pour plates. She was also influenced by her science fair teacher in high school, Mr. Dennis Taylor, who introduced her to “the wonder of science.” Lorenz applied for and was accepted to Stanford University, and paid her way by working in a lab as a work study student. There she met her future husband, an M.D./Ph.D. student, who introduced her to “life as a physician scientist.” She spent time abroad working in a hospital in London where she enjoyed a slower pace of research with increased time to step away from the bench and consider the results of her experiments. She says she quickly learned that her passion was in helping others to find work they love in the sciences. On June 26, 2018, the Department of Pathology hosted a farewell reception to celebrate Lorenz's successful career at UAB and the meaningful impact she has had on so many student's lives as director of the MSTP program. Dean Selwyn Vickers, M.D., UAB School of Medicine, spoke on her behalf, along with several colleagues and Department Chair Dr. George Netto. Many of Lorenz's former and current students were on hand to wish her well.

L TO R: GEORGE NETTO, M.D., ROBIN LORENZ, M.D., PH.D, CRAIG HOESLEY, M.D., AND SOM DEAN SELWYN VICKERS, M.D.

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A N D MOR E

UAB Pathology Conference & Committee Roundup This summer, our faculty traveled the country and the world, representing the department at conferences, meetings, and other research and clinical events. Diana Morlote, M.D., Fellow, PGY5, received a travel grant to attend the Association of Clinical Scientists 138th annual meeting, held May 16–19 in Houston, Texas. Robert Hardy, Ph.D., Professor, Laboratory Medicine, is the current president of the association. Morlote presented in the Genomic and Evidence-Based Medicine track on “Molecular and cytogenetic characterization of therapy — related myeloid neoplasms: a tertiary center experience.” Two faculty participated in UAB's 6th Annual Workshop on Metabolomics, taking place July 22­–27. Victor DarleyUsmar, Ph.D., gave the dinner lecture Tuesday on “Plotting Career Paths in Science” and Jianhua Zhang, presented “Metabolism in the Raw-the SeaHorse, the Modern Version of the Warburg Apparatus.”

Liyun Cao, Ph.D., Instructor in the Division of Lab Medicine, received the 2018 Travel Award from the American Association for Clinical Chemistry (AACC) Southeast Section to attend the organization's annual meeting in Chicago, July 29–August 2. Our own Joanne Murphy-Ullrich, Ph.D., gave the plenary talk to the Matrix Biology Europe 2018 conference in Manchester, England, and also chaired the American Society for Matrix Biology-sponsored session on ECM and fibrosis, July 21–24. Rajeev Samant, Ph.D., was a member of the Program Committee, Tumor Microenvironment Section, at the 2018 Annual American Association for Cancer Research Meeting in April, and study sections at NIH in February, on Provocative Questions R01/R21, and June on Cancer Drug Development and Design.

Sooryanarayana Varambally, Ph.D., gave several lectures in Alabama and abroad this summer. First, he visited Paris' Centre de Recherche des Cordeliers on July 6, and Life Arc in London and Cambridge University. He moved on to deliver a lecture on “Identifying New Therapeutic Targets in Cancer” at University Clinic in Ulm, Germany. Finally Varambally visited Zabgreb University in Zagreb, Croatia, a UAB partner institution, to speak on the, “Role of histone methyltransferase EZH2 in regulating oncogene tumor suppressor networks” and his cancer data mining tool, UALCAN. On July 17, back in Alabama, he lectured on “A System Biology Approach to Identify Therapeutic Targets in Cancer” at the NanoBio2018 Summit at Alabama State University in Montgomery. Elizabeth Brown, Ph.D., was an invited member of the National Cancer Institute's “Myeloma Think Tank.”

Several faculty attended the XXXII Congress of the International Academy of Pathology in Jordan, Oct. 14–18. George Netto, M.D., led a course on “Molecular Diagnostics and Genomic Applications in Cancer: A Primer for the Pathologist.” Featured speakers included: Anna Yemelyanova, M.D.,, M.D., Professor, on “Molecular Testing of Solid Tumors; and Shuko Harada, M.D., Associate Professor and Interim Director, Division of Genomic Diagnostics and Bioinformatics, on “Implementation of NextGeneration Sequencing.” Cristina Magi-Galluzzi, M.D., Ph.D., Professor, Division Director, Anatomic Pathology, also presented on ”Molecular Markers for Prostate Cancer: Necessary to Supplement Morphology?” Eltoum Isam-Eldin, M.D., Professor, Anatomic Pathology and Vice Chair Quality and Patient Safety, presented the lecture “Endoscopic FNA (EUS/ EBUS) Transforming the Way We Manage Deep-Seated Lesions.”

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X. LONG ZHENG, Division Director, Lab Medicine, was the invited speaker at three events throughout the summer. First stop, the Tri-Service Hospital and National Defense Medical College in Taipai, Taiwan, on July 3–5, where he gave talks on, “Diagnosis and Management of Thrombotic Microangiopathy;” “Advances in Thrombotic Microangiopathy Research;” and “Differential Diagnosis of TMA–the Role of ADAMTS13.” Next, Zheng lectured on “New Advances in Biology of Thrombotic Thrombocytopenic Purpura” at the New Advances in Vascular Biology Conference, sponsored by the Irish Centre for Vascular Biology, July 16 in Dublin, Ireland. On August 4, Zheng addressed the National Congress of Cardiovascular Disease, in Beijing, China, on “Targeted Delivery of Recombinant ADATMS13 for Therapy.” PROFESSOR JOSEPH CHEN (L), A HEMATOLOGIST AT TRI-SERVICE HOSPITAL, INVITED X. LONG ZHENG (R) AS A GUEST PROFESSOR FOR ONE WEEK.

From our Forensic Division, Dan Atherton, M.D., presented a poster and presentation at the annual meeting of the Association of Pathology Chairs, in San Diego on July 18. Atherton presented a poster and a presentation on “Microscopic Examination of Lesions Discovered in Anatomy Lab: An Innovative Educational Tool,” with fellow faculty member Peter Anderson. Brandi McCleskey, M.D., presented on July 23–24 as part of a statewide program to educate law enforcement personnel, attorneys, child protective services personnel, and EMS personnel on Child Injury and Death Scene Re-Enactment. Dr. McCleskey spoke on, “The Medical Examiner's Response to Sudden Unexpected Infant Death (SUID). Greg Davis, M.D., participated in a conference hosted by the National Institute of Justice concerning opioid deaths and Prescription Drug Monitoring Programs, to be held in Washington, D.C. on August 21.

John Chatham, Ph.D., was an invited speaker at the 35th meeting of the International Society of Heart Research — European Section, Amsterdam (the Netherlands), held July 16–19. The title of his presentation was, “Is O-GlcNAcylation the new phosphorylation? Department faculty presented lectures and posters at several pathology annual meetings this fall, including the American Society for Matrix Biology (ASMB, Oct. 14-17), the XXXII Congress of the International Academy of Pathology (Oct. 14–18), and the College of American Pathologists (CAP, Oct. 20–24). Shyam Bandari, Ph.D., Postdoctoral Fellow, won a travel award to travel to attend the ASMB conference for the first time, where he hosted a special interest section of “Extracellular Vesicles: The Next SMALL Thing” on Tuesday, October 14.

Joanne Murphy-Ullrich, Ph.D., Professor, is President of the ASMB this year and hosted their annual meeting in Las Vegas with the theme, “ECM Microenvironments in Disease, Aging and Regeneration.” Additional conferences in October included the American Society for Clincial Pathology (Oct. 3–5) and ESUR18 — the 25th Meeting of the EAU Section of Urological Research in Athens, Greece. Marie-Lise Eich, M.D., Postdoctoral Fellow, Pathology, presented on “UroSEEK Signature in Bladder Urothelial Carcinoma,” relating to the UroSEEK test developed with Netto.

DR. VARAMBALLY MEETS WITH COLLEAGUES AT CAMBRIDGE UNIVERSITY.

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