NSF CAREER AWARDS

Jason Gleghorn, an associate professor, received a National Science Foundation (NSF) CAREER Award to understand how the body’s adaptive immune system activates. He is developing a new class of microfluidic devices to culture an entire lymph node outside the body and study the cells’ behavior in real time.

The work has broad application to the understanding of chronic infection and inflammation, and metastatic cancer to the lymph node. It also could inform drug delivery strategies for chemotherapy and antiretroviral therapies for HIV.

A lymph node’s complex structure prevents drugs from penetrating inside to target viruses, bacteria and metastatic cancer cells that collect there. Gleghorn is interested in how immune cells go through the lymph node, and how these immune cells work and behave.

“Sometimes cells bring viruses like HIV and bacteria into the lymph node. When these foreign invaders, or metastatic tumor cells themselves, move into privileged areas called lobules within the lymph node, the drugs that work well in the rest of the body cannot get in to kill the infection,” said Gleghorn.

“We believe this is why you get recurrence of viral infection like HIV and why cancer metastasis to lymph nodes is so devastating. To-date there is no tractable way to solve this problem; we do not know how this works.” Gleghorn is developing experimental devices that can enable researchers to see, understand and image how things work and behave in the more complex organ in real time.

Initial work on the project will include developing the system to culture an entire lymph node with collaborators at University of Pennsylvania’s School of Veterinary Medicine, a unique approach that will allow the researchers to retain the organ’s complexity in its natural state. Then, in collaboration with Penn Medicine’s transplant team, Gleghorn’s research team will advance the system to enable culture and imaging of human lymph nodes.

The UD-developed device will be made from molded silicon rubber and tiny glass needles that the researchers make. They will load the lymph node into the middle of the mold, then connect the teeny-tiny glass tubes into the blood and lymphatic vessels that go into and out of the lymph node.

Using this “plumbing” the team plans to insert specific cells or drugs and track them as they move through the lymph node.

The team will collect real-time measurements to validate that what they see in this new whole-organ culture system actually replicates what can be expected inside the body.

Assistant professor Fabrizio Sergi received a National Science Foundation (NSF) CAREER award to support fundamental research in motor control that could, in the future, improve practices in neurorehabilitation for individuals with motor impairment.

With the award, Sergi is using magnetic resonance imaging (MRI) to study how the human brain and body respond to interactions with robotic devices.

Sergi develops new robots and tools to elucidate the physiology of human motor control, the body’s regulation of volnary and involuntary movements.

This work is important because movement disorders, which can limit a person’s voluntary movements or cause involuntary movements, can be difficult to treat and cause significant burdens on quality of life. Motor difficulties affect patients with a variety of diagnoses, from stroke to Parkinson’s Disease to dystonia and more.

Sergi has created a niche area by developing MRI-compatible robots to study how the brain and muscle work during physical interaction with robotic devices. Many robots used in medical research can’t be used with an MRI machine, making it difficult to study brain activity during their use.

Sergi is a world leader in developing robotic tools that are compatible with MRI imaging techniques. For example, he has developed a wrist-controlled robotic device that can be controlled like a joystick. While the user moves the device and responds to actions applied from the robot, their brain is scanned by the MRI machine, revealing new insights about what drives movements during human-robot interaction.

By developing a better understanding of movements even in healthy subjects, Sergi and experts can figure out robotbased interventions to help those with movement disorders. This insight is much needed because, currently, there is a poor fundamental understanding of how exactly the human brain and muscles interact with robots during robot-assisted motor tasks.

Most studies on human physiology are focused on the humans themselves, but when you’re studying how humans work with robotic devices, it’s more complicated.

“There are additional neuromuscular mechanisms that we use to control interaction with active agents, such as co-contracting our muscles, or relying on fast reactive responses (also called reflexes), but these processes have not been studied in the context of humanrobot interaction,” said Sergi.

Ultimately, Sergi and his students are paving the way for personalized robotic devices people could someday use to recover from neurological injuries that affect motor function.