Throughout his career, Brian Litt has fabricated tools that support international collaboration, produced findings that have led to significant breakthroughs, and mentored the next generation of researchers tackling neurological disorders. (Image: iStock Photo/Alona Siniehina)
When Brian Litt of the Perelman School of Medicine and School of Engineering and Applied Science began treating patients as a neurologist, he found that the therapies and treatments for epilepsy were mostly reliant on traditional pharmacological interventions, which had limited success in changing the course of the disease.
People with epilepsy are often prescribed anti-seizure medications, and, while they are effective for many, about 30% of patients still continue to experience seizures. Litt sought new ways to offer patients better treatment options by investigating a class of devices that electronically stimulate cells in the brain to modulate activity known as neurostimulation devices.
Litt’s research on implantable neurostimulation devices has led to significant breakthroughs in the technology and has broadened scientists’ understanding of the brain. This work started not long after he came to Penn in 2002 with licensing algorithms to help drive a groundbreaking device by NeuroPace, the first closed-loop, responsive neurostimulator to treat epilepsy.
Building on this work, Litt noted in 2011 how the implantable neurostimulation devices being used at the time had rigid wires that didn’t conform to the brain’s surface, and he received support from CURE Epilepsy to accelerate the development of newer, flexible wires to monitor and stimulate the brain.
“CURE is one of the epilepsy community’s most influential funding organizations,” Litt says. “Their support for my lab has been incredibly helpful in enabling the cutting-edge research that we hope will change epilepsy care for our patients.”
Penn Engineering’s newly established ASSET Center aims to make AI-enabled systems more “safe, explainable and trustworthy” by studying the fundamentals of the artificial neural networks that organize and interpret data to solve problems.
ASSET’s first funding collaboration is with Penn’s Perelman School of Medicine (PSOM) and the Penn Institute for Biomedical Informatics (IBI). Together, they have launched a series of seed grants that will fund research at the intersection of AI and healthcare.
Teams featuring faculty members from Penn Engineering, Penn Medicine and the Wharton School applied for these grants, to be funded annually at $100,000. A committee consisting of faculty from both Penn Engineering and PSOM evaluated 18 applications and judged the proposals based on clinical relevance, AI foundations and potential for impact.
Artificial intelligence and machine learning promise to revolutionize nearly every field, sifting through massive amounts of data to find insights that humans would miss, making faster and more accurate decisions and predictions as a result.
Applying those insights to healthcare could yield life-saving benefits. For example, AI-enabled systems could analyze medical imaging for hard-to-spot tumors, collate multiple streams of disparate patient information for faster diagnoses or more accurately predict the course of disease.
Given the stakes, however, understanding exactly how these technologies arrive at their conclusions is critical. Doctors, nurses and other healthcare providers won’t use such technologies if they don’t trust that their internal logic is sound.
“We are developing techniques that will allow AI-based decision systems to provide both quantifiable guarantees and explanations of their predictions,” says Rajeev Alur, Zisman Family Professor in Computer and Information Science and Director of the ASSET Center. “Transparency and accuracy are key.”
“Development of explainable and trustworthy AI is critical for adoption in the practice of medicine,” adds Marylyn Ritchie, Professor of Genetics and Director of the Penn Institute for Biomedical Informatics. “We are thrilled about this partnership between ASSET and IBI to fund these innovative and exciting projects.”
Seven projects were selected in the inaugural class, including projects from Dani S. Bassett, J. Peter Skirkanich Professor in the Departments of Bioengineering, Electrical and Systems Engineering, Physics & Astronomy, Neurology, and Psychiatry, and several members of the Penn Bioengineering Graduate Group: Despina Kontos, Matthew J. Wilson Professor of Research Radiology II, Department of Radiology, Penn Medicine and Lyle Ungar, Professor, Department of Computer and Information Science, Penn Engineering; Spyridon Bakas, Assistant Professor, Departments of Pathology and Laboratory Medicine and Radiology, Penn Medicine; and Walter R. Witschey, Associate Professor, Department of Radiology, Penn Medicine.
Optimizing clinical monitoring for delivery room resuscitation using novel interpretable AI
Elizabeth Foglia, Associate Professor, Department of Pediatrics, Penn Medicine and the Children’s Hospital of Philadelphia
Dani S. Bassett, J. Peter Skirkanich Professor, Departments of Bioengineering and Electrical and Systems Engineering, Penn Engineering
This project will apply a novel interpretable machine learning approach, known as the Distributed Information Bottleneck, to solve pressing problems in identifying and displaying critical information during time-sensitive clinical encounters. This project will develop a framework for the optimal integration of information from multiple physiologic measures that are continuously monitored during delivery room resuscitation. The team’s immediate goal is to detect and display key target respiratory parameters during delivery room resuscitation to prevent acute and chronic lung injury for preterm infants. Because this approach is generalizable to any setting in which complex relations between information-rich variables are predictive of health outcomes, the project will lay the groundwork for future applications to other clinical scenarios.
The Heilmeier Award honors a Penn Engineering faculty member whose work is scientifically meritorious and has high technological impact and visibility. It is named for the late George H. Heilmeier, a Penn Engineering alumnus and member of the School’s Board of Advisors, whose technological contributions include the development of liquid crystal displays and whose honors include the National Medal of Science and Kyoto Prize.
Bassett, who also holds appointments in Physics & Astronomy in Penn Arts & Sciences and in Neurology and Psychiatry in the Perelman School of Medicine, is a pioneer in the field of network neuroscience, an emerging subfield which incorporates elements of mathematics, physics, biology and systems engineering to better understand how the overall shape of connections between individual neurons influences cognitive traits. They lead the Complex Systems lab, which tackles problems at the intersection of science, engineering and medicine using systems-level approaches, exploring fields such as curiosity, dynamic networks in neuroscience, and psychiatric disease.
Bassett will deliver the 2022-23 Heilmeier Award Lecture in Spring 2023.
We hope you will join us for the 2022 Grace Hopper Distinguished Lecture by Dr. Jennifer Lewis, presented by the Department of Bioengineering and hosted by Dani S. Bassett, J. Peter Skirkanich Professor in Bioengineering, Electrical and Systems Engineering, Physics & Astronomy, Neurology and Psychiatry.
Date: Thursday, December 8, 2022
Start Time: 3:30 PM EST
Location: Glandt Forum, Singh Center for Nanotechnology, 3205 Walnut Street, Philadelphia, PA 19104
Join us after the live lecture for a light reception!
Daphna Shohamy, Ph.D.
Speaker: Daphna Shohamy, Ph.D.
Kavli Professor of Brain Science, Co-Director of the Kavli Institute for Brain Science, Professor in the Department of Psychology & Zuckerman Mind Brain Behavior Institute Columbia University
From robots to humans, the ability to learn from experience turns a rigid response system into a flexible, adaptive one. In the past several decades, major advances have been made in understanding how humans and other animals learn from experience to make decisions. However, most of this progress has focused on rather simple forms of stimulus-response learning, such as automatic responses or habits. In this talk, I will turn to consider how past experience guides more complex decisions, such as those requiring flexible reasoning, inference, and deliberation. Across a range of behavioral contexts, I will demonstrate a critical role for memory in such decisions and will discuss how multiple brain regions interact to support learning, what this means for how memories are used, and the consequences for how decisions are made. Uncovering the pervasive role of memory in decision-making challenges the way we think about what memory is for, suggesting that memory’s primary purpose may be to guide future behavior and that storing a record of the past is just one way to do so.
Dr. Shohamy Bio:
Daphna Shohamy, PhDis a professor at Columbia University where she co-directs the Kavli Center for Neural Sciences and is Associate Director of the Zuckerman Mind, Brain Behavior Institute. Dr. Shohamy’s work focuses on the link between memory, and decision-making. Combining brain imaging in healthy humans with studies of patients with neurological and psychiatric disorders, Dr. Shohamy seeks to understand how the brain transforms experiences into memories; how memories shape decisions and actions; and how motivation and exploration affect human behavior.
Information on the GraceHopper Lecture: In support of its educational mission of promoting the role of all engineers in society, the School of Engineering and Applied Science presents the GraceHopper Lecture Series. This series is intended to serve the dual purpose of recognizing successful women in engineering and of inspiring students to achieve at the highest level.
Rear Admiral GraceHopper was a mathematician, computer scientist, systems designer and the inventor of the compiler. Her outstanding contributions to computer science benefited academia, industry and the military. In 1928 she graduated from Vassar College with a B.A. in mathematics and physics and joined the Vassar faculty. While an instructor, she continued her studies in mathematics at Yale University where she earned an M.A. in 1930 and a Ph.D. in 1934. GraceHopper is known worldwide for her work with the first large-scale digital computer, the Navy’s Mark I. In 1949 she joined Philadelphia’s Eckert-Mauchly, founded by the builders of ENIAC, which was building UNIVAC I. Her work on compilers and on making machines understand ordinary language instructions lead ultimately to the development of the business language, COBOL. GraceHopper served on the faculty of the Moore School for 15 years, and in 1974 received an honorary degree from the University. In support of the accomplishments of women in engineering, each department within the School invites a prominent speaker for a one or two-day visit that incorporates a public lecture, various mini-talks and opportunities to interact with undergraduate and graduate students and faculty.
CPE4H is one of the focal points of Penn Engineering signature initiative on Engineering Health.
The Penn Center for Precision Engineering for Health (CPE4H) was established late last year to accelerate engineering solutions to significant problems in healthcare. The center is one of the signature initiatives for Penn’s School of Engineering and Applied Science and is supported by a $100 million commitment to hire faculty and support new research on innovative approaches to those problems.
Acting on that commitment, CPE4H solicited proposals during the spring of 2022 for seed grants of $80K per year for two years for research projects that address healthcare challenges in several key areas of strategic importance to Penn: synthetic biology and tissue engineering, diagnosis and drug delivery, and the development of innovative devices. While the primary investigators (PIs) for the proposed projects were required to have a primary faculty appointment within Penn Engineering, teams involving co-PIs and collaborators from other schools were eligible for support. The seed program is expected to continue for the next four years.
“It was a delight to read so many novel and creative proposals,” says Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and the Inaugural Director of CPE4H. “It was very hard to make the final selection from a pool of such promising projects.”
Judged on technical innovation, potential to attract future resources, and ability to address a significant medical problem, the following research projects were selected to receive funding.
Evolving and Engineering Thermal Control of Mammalian Cells
Led by Lukasz Bugaj, Assistant Professor in Bioengineering, this project will engineer molecular switches that can be toggled on and off inside mammalian cells at near-physiological temperatures. Successful development of these switches will provide new ways to communicate with cells, an advance that could be used to make safer and more effective cellular therapies. The project will use directed evolution to generate and find candidate molecular tools with the desired properties. Separately, the research will also develop new technology for manipulating cellular temperature in a rapid and programmable way. Such devices will enhance the speed and sophistication of studies of biological temperature regulation.
A Quantum Sensing Platform for Rapid and Accurate Point-of-Care Detection of Respiratory Viral Infections
Combining microfluidics and quantum photonics, PI Liang Feng, Professor in Materials Science and Engineering and Electrical and Systems Engineering, Ritesh Agarwal, Professor in Materials Science Engineering, and Shu Yang, Joseph Bordogna Professor in Materials Science and Engineering and Chemical and Biomolecular Engineering, are teaming up with Ping Wang, Professor of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine, to design, build and test an ultrasensitive point-of-care detector for respiratory pathogens. In light of the COVID-19 pandemic, a generalizable platform for rapid and accurate detection of viral pathogenesis would be extremely important and timely.
Versatile Coacervating Peptides as Carriers and Synthetic Organelles for Cell Engineering
PI Amish Patel, Associate Professor in Chemical and Biomolecular Engineering, and Matthew C. Good, Associate Professor of Cell and Developmental Biology in the Perelman School of Medicine and in Bioengineering, will design and create small proteins that self-assemble into droplet-like structures known as coacervates, which can then pass through the membranes of biological cells. Upon cellular entry, these protein coacervates can disassemble to deliver cargo that modulates cell behavior or be maintained as synthetic membraneless organelles. The team will design new chemistries that will facilitate passage across cell membranes, and molecular switches to sequester and release protein therapeutics. If successful, this approach could be used to deliver a wide range of macromolecule drugs to cells.
Towards an Artificial Muscle Replacement for Facial Reanimation
Cynthia Sung, Gabel Family Term Assistant Professor in Mechanical Engineering and Applied Mechanics and Computer Information Science, will lead a research team including Flavia Vitale, Assistant Professor of Neurology and Bioengineering, and Niv Milbar, Assistant Instructor in Surgery in the Perelman School of Medicine. The team will develop and validate an electrically driven actuator to restore basic muscle responses in patients with partial facial paralysis, which can occur after a stroke or injury. The research will combine elements of robotics and biology, and aims to produce a device that can be clinically tested.
“These novel ideas are a great way to kick off the activities of the center,” says Hammer. “We look forward to soliciting other exciting seed proposals over the next several years.”
Brian Litt, MD, Professor in Neurology, Neurosurgery and Bioengineering and Director of the Penn Epilepsy Center, has received a 2022 Landis Award for Outstanding Mentorship from the National Institute of Neurological Disorders and Stroke (NINDS). This award honors Litt’s dedication to superior mentorship and training in neuroscience research. The award includes $100,000 in the form of a supplement to an existing NINDS grant to support his efforts to foster the career advancement of additional trainees.
Jennifer E. Phillips-Cremins (upper left) and members of her lab.
Each year, the National Institutes of Health (NIH) recognizes exceptionally creative scientists through its High-Risk, High-Reward Research Program. The four awards granted by this program are designed to support researchers whose “out of the box” and “trailblazing” ideas have the potential for broad impact.
Jennifer E. Phillips-Cremins, Associate Professor and Dean’s Faculty Fellow in Penn Engineering’s Department of Bioengineering and the Perelman School of Medicine’s Department of Genetics, is one such researcher. As a recipient of an NIH Director’s Pioneer Award, she will receive $3.5 million over five years to support her work on the role that the physical folding of chromatin plays in the encoding of neural circuit and synapse properties contributing to long-term memory.
Phillips-Cremins’ award is one of 106 grants made through the High-Risk, High-Reward program this year, though she is only one of 10 to receive the Pioneer Award, which is the program’s largest funding opportunity.
“The science put forward by this cohort is exceptionally novel and creative and is sure to push at the boundaries of what is known,” said NIH Director Francis S. Collins.
Phillips-Cremins’ research is in the general field of epigenetics, the molecular and structural modifications that allow the genome — an identical copy of which is found in each cell — to express genes differently at different times and in different parts of the body. Within this field, her lab focuses on higher-order folding patterns of the DNA sequence, which bring distant sets of genes and regulatory elements into close proximity with one another as they are compressed inside the cell’s nucleus.
Previous work from the Cremins lab has investigated severe genome misfolding patterns common across a class of genetic neurological disorders, including fragile X syndrome, Huntington’s disease, ALS and Friedreich’s ataxia.
With the support of the Pioneer Award, she and the members of her lab will extend that research to a more fundamental question of neuroscience: how memory is encoded over decades, despite the rapid turnover of the relevant proteins and RNA sequences within the brain’s synapses.
“Our long-term goals are to understand how, when and why pathologic genome misfolding leads to synaptic dysfunction by way of disrupted gene expression,” said Phillips-Cremins, “as well as to engineer the genome’s structure-function relationship to reverse pathologic synaptic defects in debilitating neurological diseases.”
Rebecca Kamen, Penn artist-in-residence and visiting scholar, has a new exhibition titled “Reveal: The Art of Reimagining Scientific Discovery” at American University Museum at the Katzen Arts Center that explores curiosity and the creative process across art and science. (Image: Greg Staley)
Rebecca Kamen, Penn artist-in-residence and visiting scholar, has long been interested in science and the natural world. As a Philadelphia native and an artist with a 40-plus-year career, her intersectional work sheds light on the process of scientific discovery and its connections to art, with previous exhibitions that celebrate Apollo 11’s “spirit of exploration and discovery” to new representations of the periodic table of elements.
Now, in her latest exhibition, Kamen has created a series of pieces that highlight how the creative processes in art and science are interconnected. In “Reveal: The Art of Reimagining Scientific Discovery,” Kamen chronicles her own artistic process while providing a space for self-reflection that enables viewers to see the relationship between science, art, and their own creativity.
The exhibit, on display at the Katzen Art Center at American University, was inspired by the work of Penn professor Dani Bassett and American University professor Perry Zurn, the exhibit’s faculty sponsor. The culmination of three years of work, “Reveal” features collaborations with a wide range of scientists, including philosophers at American University, microscopists at the National Institutes of Health studying SARS-CoV-2 , and researchers in Penn’s Complex Systems Lab and the Addiction, Health, and Adolescence (AHA!) Lab.
“Reveal: The Art of Reimagining Scientific Discovery,” presented by the Alper Initiative for Washington Art and curated by Sarah Tanguy, is on display at the American University Museum in Washington, D.C., until Dec. 12.
The exhbition catalog, which includes an essay on “Radicle Curiosity” by Perry Zurn and Dani S. Bassett, can be viewed online.
Flavia Vitale, assistant professor of neurology, bioengineering, and physical medicine and rehabilitation, and founder of the multidisciplinary Vitale Lab. (Image: Penn Medicine News)
Neurology, bioengineering, and physical medicine and rehabilitation might not seem like three disciplines that fit together, but for Flavia Vitale, an assistant professor of all three, it makes perfect sense. As the director and principal investigator at the Vitale Lab, her research focuses on developing new technologies that help to study how the brain and neuromuscular systems function.
Years ago, while she was working at Rice University developing new materials and devices that work in the body in a safer, more effective way, former president Barack Obama launched the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, aimed at revolutionizing the understanding of the human brain. This emphasis on how little is known about brain structure and function inspired Vitale to refocus her research on developing technology and materials that will help researchers solve the mysteries of the brain.
In 2018, she joined the faculty at the Perelman School of Medicine as an assistant professor of neurology, bioengineering, and physical medicine and rehabilitation, and founded the multidisciplinary Vitale Lab, where her team develops cutting edge materials and devices that will someday help clinicians diagnose and treat patients with complicated brain and neurological conditions. She is also one of the engineers looking forward to using new combined clinical/research facilities in neuroscience at Penn Medicine’s new Pavilion where new neurotechnoloigies will be developed and tested.
“My main goal is to create tools that can help solve mysteries of the brain, and address the needs of clinicians,” she says.
“My lab was recently awarded two grants totaling $4.5 million from the National Institute of Neurological Disorders and Stroke. In order to obtain more precise insights, noninvasively, into brain activity to improve gene therapy treatments for a range of diagnoses, from Parkinson’s disease to glioblastoma. The first grant is designated for the development of a novel surgical device for delivering gene-based therapeutics to the brain. The second is for optimization and pre-clinical validation of a novel EEG electrode technology, which uses a soft, flexible, conductive nanomaterial rather than metal and gels. We hope to confirm that these technologies work as well as, if not better than existing ones.”
Shreya Parchure, a recent graduate of Penn Bioengineering, was selected by a committee of faculty for a 2021 Rose Award from the Center for Undergraduate Research and Fellowships (CURF). The Rose Award recognizes outstanding undergraduate research projects completed by graduating seniors under the supervision of a Penn faculty member and carries with it a $1,000 award. Parchure’s project, titled “BDNF Gene Polymorphism Predicts Response to Continuous Theta Burst Stimulation (cTBS) in Chronic Stroke Patients,” was done under the supervision of Roy H. Hamilton, Associate Professor in Neurology and Physical Medicine and Rehabilitation and director of the Laboratory for Cognition and Neural Stimulation in the Perelman School of Medicine. Parchure’s work in Hamilton’s lab previously resulted in a 2020 Goldwater Scholarship.
