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ASSET Center Inaugural Seed Grants Will Fund Trustworthy AI Research in Healthcare

by Devorah Fischler

Illustration credit: Melissa Pappas

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.

Read the full list of projects and abstracts in Penn Engineering Today.

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Two Penn Bioengineering Professors Receive PCI Innovation Awards

From left to right: Marc Singer, Kirsten Leute, D. Kacy Cullen, Dan Huh, Doug Smith, and Haig Aghajanian

Two Penn Bioengineering Professors have received awards in the 7th Annual Celebration of Innovation from the Penn Center for Innovation (PCI).

Dongeun (Dan) Huh, Associate Professor in the Department of Bioengineering, was named the 2022 Inventor of the Year. D. Kacy Cullen, Associate Professor of Neurosurgery with a secondary appointment in Bioengineering, accepted the Deal of the Year Award on behalf of his company Innervace along with Co-Scientific Founder Douglas H. Smith, Robert A. Groff Professor of Teaching and Research in Neurosurgery in the Perelman School of Medicine.

PCI is interdisciplinary center for technology commercialization and startups in the Penn community. Their 7th Annual Celebration, held on December 6, 2022 at the Singh Center for Nanotechnology, honored Penn researchers and inventors whose achievements were a particular highlight of the fiscal year.

Huh was honored in recognition of his “extraordinary innovations in bioengineering tools.” The Huh Biologically Inspired Engineering Systems Laboratory (BIOLines) Laboratory is a leader in tissue engineering and cell-based smart biomedical devices, particularly in the “lab-on-a-chip” field of devices which can approximate the functioning of organs. Their research has been featured by the National Science Foundation (NSF, video below) and Wired, and has received a competitive Chan Zuckerberg Initiative (CZI) grant. Most recently, their “implantation-on-a-chip” technology has been used to better understand early-stage pregnancy. Huh and former lab member Andrei Georgescu (Ph.D. in Bioengineering, 2021) founded the spinoff company Vivodyne to bring this organ-on-a-chip technology to the industry sector. Fast Company included Vivodyne in a list of “most innovative” companies.

Innervace, represented by Cullen and Smith, took home the Deal of the Year award in recognition of its “successful Series A funding.” Innervace is another Penn spinoff which develops “anatomically inspired living scaffolds for brain pathway reconstruction.” Innervace raised up to $40 million in Series A financing to “accelerate a new cell therapy modality for the treatment of neurological disorders.” The Cullen Lab at Penn Medicine combines neuroengineering, regenerative medicine, and the study of neurotrauma to improve understanding of neural injury and develop cutting-edge neural tissue engineering-based treatments to promote regeneration and restore function.

Read the full list of 2022 PCI Award winners here.

Read more stories featuring Dan Huh and D. Kacy Cullen.

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Student Spotlight: Bella Mirro

Bella Mirro (BE 2023)

Bella Mirro, a fourth year student in Bioengineering who also minors in Chemistry, spoke with 34th Street Magazine about her many roles at Penn, including being Co–President of Shelter Health Outreach Program (SHOP), a Research Assistant in lab of Michal A. Elovitz, the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health at Penn Medicine, and a Penn Engineering Council Marketing Team Member. In this Q&A, she discusses her research in women’s health and her passions for accessible healthcare, serving Philadelphia’s homeless community, and good food.

Read “Ego of the Week: Bella Mirro” in 34th Street.

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Penn Bioengineering Alumna Cynthia Reinhart-King Invited to White House Summit

Cynthia Reinhart-King

Cynthia Reinhart-King, Cornelius Vanderbilt Professor of Engineering and Professor of Biomedical Engineering at Vanderbilt University, was one of a handful of experts invited to take part in the White House Summit in Biotechnology and Biomanufacturing on September 14, 2022 in Washington, D.C. Reinhart-King and her colleagues gathered to discuss “bio-based solutions to global challenges ranging from food security and climate change to health security and supply chain disruptions.”

Reinhart-King is an alumna of Penn Bioengineering, graduating with her doctorate in 2006.  She delivered the Grace Hopper Lecture for Penn Engineering in 2019, and was named President-Elect of the Biomedical Engineering Society (BMES), the largest professional society for biomedical engineers, in 2021.

Read “Preeminent engineering researcher takes part in national summit on biotechnology and biomanufacturing” in Vanderbilt University Research News.

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CEMB Researchers Find that Disease Can Change the Physical Structure of Cells

by Ebonee Johnson

In these super-resolution images of tendon cell nuclei, the color coding represents chromatin density map, from low density in blue to high density in red. Comparing a healthy human tendon cell nucleus (left) to one diagnosed with tendinosis (right) shows that disease alters the spatial localization and compaction of chromatin.

Researchers from Penn’s Center for Engineering Mechanobiology (CEMB) have discovered that cells change the physical structure of their genome when they’re affected by disease.

In a recent study published in Nature Biomedical Engineering, the team detailed what they found when they closely observed the nucleus of cells inside connective tissues deteriorating as a result of tendinosis, which is the chronic condition that results from a tendon repeatedly suffering small injuries that don’t heal correctly. Using the latest super-resolution imaging techniques, they found that the tendon cells involved in maintaining the tissue’s structure in a diseased microenvironment improperly reorder their chromatin — the DNA-containing material that chromosomes are composed of — when attempting to repair.

This and other findings highlighted in the report point to the possibility of new treatments, such as small-molecule therapies, that could restore order to the affected cells.

“Interestingly, we were able to explain the role of mechanical forces on the 3-D organization of chromatin by developing a theory that integrates fundamental thermodynamic principles (physics) with the kinetics of epigenetic regulation (biology),” said study co-author and CEMB Director Vivek Shenoy in a news release from Penn Medicine News.

The CEMB, one of 18 active interdisciplinary research centers funded by the National Science Foundation’s Science and Technology Center (STC) program, brings together dozens of researchers from Penn Engineering and the Perelman School of Medicine, as well as others spread across campus and at partner institutions around the world.

With its funding recently renewed for another five years, the CEMB has entered  into a new phase of its mission, centered on the nascent concept of “mechanointelligence,” which is exemplified by studies like this one. While mechanobiology is the study of the physical forces that govern the behavior of cells and their communication with their neighbors, mechanointelligence adds another layer of complexity: attempting to understand the forces that allow cells to sense, remember and adapt to their environments.

Ultimately, harnessing these forces would allow researchers to help multicellular organisms — plants, animals and humans — better adapt to their environments as well.

Read “Aberrant chromatin reorganization in cells from diseased fibrous connective tissue in response to altered chemomechanical cues” at Nature Biomedical Engineering.

Read “The Locked Library: Disease Causes Cells to Reorder Their DNA Incorrectly” at Penn Medicine News.

This story originally appeared in Penn Engineering Today.

Vivek Shenoy is Eduardo D. Glandt President’s Distinguished Professor in Materials Science and Engineering, Bioengineering, and in Mechanical Engineering and Applied Mechanics.

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‘Curious Minds: The Power of Connection’

Twin siblings and scholars Dani S. Bassett of Penn and Perry Zurn of American University collaborated over half a dozen years to write “Curious Minds: The Power of Connection.” (Image: Tony and Tracy Wood Photography)

With appointments in the Departments of Bioengineering and Electrical and Systems Engineering, as well as the Department of Physics and Astronomy in Penn Arts & Science, and the Departments of Neuroscience and Psychiatry in Penn Perelman’s School of Medicine, Dani S. Bassett is no stranger to following the thread of an idea, no matter where it might lead.

Curious Minds book cover

Those wide-ranging fields and disciplines orbit around an appropriate central question: how does the tangle of neurons in our brains wire itself up to learn new things? Bassett, J. Peter Skirkanich Professor and director of the Complex Systems Lab, studies the relationship between the shape of those networks of neurons and the brain’s abilities, especially the way the shape of the network grows and changes with the addition of new knowledge.

 

To get at the fundamentals of the question of curiosity, Bassett needed to draw on even more disciplines. Fortunately, they didn’t have to look far; Bassett’s identical twin is Perry Zurn, a professor of philosophy at American University, and the two have investigated the many different ways a person can exhibit curiosity.

Bassett and Zurn have now published a new book on the subject. In Curious Minds: The Power of Connection, the twins draw on their previous research, as well as an expansive network of ideas from philosophy, history, education and art.

In an interview with The Guardian, Bassett explains how these threads wove together:

“It wasn’t clear at the beginning of our careers that we would even ever have a chance to write a book together because our areas were so wildly different,” Bassett says – but then, as postgraduates, Zurn was studying the philosophy of curiosity while Bassett was working on the neuroscience of learning. “And so that’s when we started talking. That talking led to seven years of doing research together,” Bassett says. “This book is a culmination of that.”

How exactly do philosophy and neuroscience complement each other? It all starts with the book’s first, and most deceptively simple question: what is curiosity? “Several investigators in science have underscored that perhaps the field isn’t even ready to define curiosity and how it’s different from other cognitive processes,” says Bassett. The ambiguity in the neuroscience literature motivated Bassett to turn to philosophy, “where there are really rich historical definitions and styles and subtypes that we can then put back into neuroscience and ask: ‘Can we see these in the brain?’”

Curious Minds: The Power of Connection is available now. Read Amelia Tait’s review “Are you a busybody, a hunter or a dancer? A new book about curiosity reveals all,” in The Guardian. 

This story originally appeared in Penn Engineering Today.

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2022 CAREER Award Recipient: Lukasz Bugaj

by Melissa Pappas

Lukasz Bugaj (illustration by Melissa Pappas)

Therapies that use engineered cells to treat diseases, infections and chronic illnesses are opening doors to solutions for longstanding medical challenges. Lukasz Bugaj, Assistant Professor in Bioengineering, has been awarded a National Science Foundation CAREER Award for research that may be key to opening some of those doors.

Such cellular therapies take advantage of the complex molecular mechanisms that cells naturally use to interact with one another, enabling them to be more precise and less toxic than traditional pharmaceutical drugs, which are based on simpler small molecules. Cellular therapies that use engineered immune system cells, for example, have recently been shown to be highly successful in treating certain cancers and protecting against viral infections.

However, there is still a need to further fine-tune the behavior of cells in these targeted therapies. Bugaj and colleagues are addressing that need by developing new ways to communicate with engineered cells once they are in the body, such as turning molecular events on and off at specific times.

The research team recently discovered that both temperature and light can act as triggers of a specific fungal protein, dynamically controlling its location within a mammalian cell. By using light or temperature to instruct that protein to migrate toward or away from the cell’s membrane, Bugaj and his colleagues showed how it could serve as a key component in controlling the behavior of human cells.

Read the full story in Penn Engineering Today.

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Konrad Kording on the Future of Brain-Computer Interfaces

Konrad Kording (Photo by Eric Sucar)

Though the technology for brain-computer interfaces (or BCI’s) has existed for decades, recent strides have been made to create BCI devices which are safer, smaller, and more effective. Konrad Kording, Nathan Francis Mossell University Professor in Bioengineering, Neuroscience, and Computer and Information Science, helps to elucidate the potential future of this technology in a recent feature in Wired. In the article, he discusses the “invasive” aspects of previous BCI technology, in contrast to recent innovations, such as a new device by Synchron, which do not require surgery and are consequently much less risky:

“The device, called a Stentrode, has a mesh-like design and is about the length of a AAA battery. It is implanted endovascularly, meaning it’s placed into a blood vessel in the brain, in the region known as the motor cortex, which controls movement. Insertion involves cutting into the jugular vein in the neck, snaking a catheter in, and feeding the device through it all the way up into the brain, where, when the catheter is removed, it opens up like a flower and nestles itself into the blood vessel’s wall. Most neurosurgeons are already up to speed on the basic approach required to put it in, which reduces a high-risk surgery to a procedure that could send the patient home the very same day. ‘And that is the big innovation,” Kording says.

Read “The Age of Brain-Computer Interfaces Is on the Horizon” in Wired.

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Kevin Johnson Appointed Senior Fellow at Penn LDI

Kevin B. Johnson, M.D., M.S.

Congratulations to Kevin B. Johnson, David L. Cohen University Professor, on his recent appointed as a Senior Fellow in the Leonard Davis Institute of Health Economics at the University of Pennsylvania (Penn LDI). Johnson, an expert in health care innovation and health information technology, holds appointments in Biostatistics, Epidemiology and Informatics in the Perelman School of Medicine and Computer and Information Science in the School of Engineering and Applied Science. He also holds secondary appointments in Bioengineering, Pediatrics, and in the Annenberg School of Communication and is Vice President for Applied Informatics in the University of Pennsylvania Health System.

Penn LDI is Penn’s hub for health care delivery, health policy, and population health, we connect and amplify experts and thought-leaders and train the next generation of researchers. Johnson joins over 500 Fellows from across all of Penn’s schools, the University of Pennsylvania Health System, and the Children’s Hospital of Philadelphia. Johnson brings expertise in Health Care Innovation, Health Information Technology, Medication Adherence, and Social Media to his new fellowship and has extensively studied healthcare informatics with the goal of improving patient care.

Learn more about Penn LDI on their website.

Learn more about Johnson’s research on his personal website.

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Alexander Buffone Appointed Assistant Professor at New Jersey Institute of Technology

Alexander Buffone, Ph.D.

Penn Bioengineering is proud to congratulate Alexander Buffone, Ph.D. on his appointment as Assistant Professor in the Department of Biomedical Engineering at New Jersey Institute of Technology. His appointment began in the Spring of 2022.

Buffone got his Ph.D. in Chemical Engineering from SUNY Buffalo in Buffalo, NY in 2012, working with advisor Sriram Neelamegham, Professor of Chemical and Biological Engineering. Buffone completed previous postdoctoral studies at Roswell Park Comprehensive Cancer Center with Joseph T.Y. Lau, Distinguished Professor of Oncology in the department of Cellular and Molecular Biology. Upon coming to Penn in 2015, Buffone has worked in the Hammer Lab under advisor Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and in Chemical and Biomolecular Engineering, first as a postdoc and later a research associate. Buffone also spent a year as a Visiting Scholar in the Center for Bioengineering and Tissue Regeneration, directed by Valerie M. Weaver, Professor at the University of California, San Francisco in 2019.

While at Penn, Buffone was a co-investigator on an R21 grant through the National Institutes of Health (NIH) which supported his time as a research associate. Buffone is excited to start his own laboratory where he plans to train a diverse set of trainees.

Buffone’s research area lies at the intersection of genetic engineering, immunology, and glycobiology and addresses how to specifically tailor the trafficking and response of immune cells to inflammation and various diseases. The work seeks to identify and subsequently modify critical cell surface and intracellular signaling molecules governing the recruitment of various blood cell types to distal sites. The ultimate goal of his research is to tailor and personalize the innate and adaptive immune response to specific diseases on demand.

“None of this would have been possible without the unwavering support of all of my mentors, past and present, and most especially Dan Hammer,” Buffone says. “His support in helping me transition into an independent scientist and his understanding of my outside responsibilities as a dad with two young children is truly the reason why I am standing here today. It’s a testament to Dan as both a person and a mentor.”