Penn Engineering announced the faculty recipients of the 2023 Student Choice Awards (formerly the Teaching and Advising Awards). Each year, the Penn Engineering undergraduate student body thoughtfully selects the recipients of these awards for their dedication in teaching, mentorship and student advocacy. This year also features two new awards, the Student Advocacy Award and the Undergraduate Research Mentoring Award.
Brit Shields, Senior Lecturer in Bioengineering, is the inaugural recipient of the Student Advocacy Award. This award is presented to a member of the Penn Engineering faculty by the Underrepresented Student Advisory Board in Engineering in recognition of their outstanding commitment to women and underrepresented student advocacy, equity and inclusion.
Dr. Shields poses with her award at the annual Penn Engineering Awards Ceremony.
Shields completed a Ph.D. at Penn in 2015 in History and Sociology of Science, with a dissertation on scientific diplomacy through the example of Richard Courant and New York University, where Shields completed an M.A. in Humanities and Social Thought: Science Studies.
She was promoted to Senior Lecturer in Bioengineering in 2019. She has brought her expertise in the history and sociology of science to her leading role in developing and improving the ethics curriculum for all students in the School of Engineering and Applied Science.
Read other stories featuring Brit Shields in the BE Blog.
Read the full list of 2023 Penn Engineering Student Choice Award Winners in Penn Engineering Today.
Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer, with AIMBE Fellows representing the top 2% of medical and biological engineers. College membership honors those who have made outstanding contributions to “engineering and medicine research, practice, or education” and to “the pioneering of new and developing fields of technology, making major advancements in traditional fields of medical and biological engineering, or developing/implementing innovative approaches to bioengineering education.”
Nominated and reviewed by peers and members of the College of Fellows, de la Fuente was elected Fellow “for the development of novel antimicrobial peptides designed using principles from computation, engineering and biology.”
A formal ceremony will be held during the AIMBE Annual Event in Arlington, Virginia on March 27, 2023, where de la Fuente will be inducted along with 140 colleagues who make up the AIMBE College of Fellows Class of 2023.
AIMBE Fellows are among the most distinguished medical and biological engineers, including 3 Nobel Prize laureates and 17 Fellows having received the Presidential Medal of Science and/or Technology and Innovation, along with 205 having been inducted into the National Academy of Engineering, 105 into the National Academy of Medicine and 43 into the National Academy of
Sciences.
nucleus and membrane of pathogen micro organisms in blue background
Up to 50 percent of cancer-signaling proteins once believed to be immune to drug treatments due to a lack of targetable protein regions may actually be treatable, according to a new study from the Perelman School of Medicine at the University of Pennsylvania. The findings, published this month in Nature Communications, suggest there may be new opportunities to treat cancer with new or existing drugs.
Researchers, clinicians, and pharmacologists looking to identify new ways to treat medical conditions—from cancer to autoimmune diseases—often focus on protein pockets, areas within protein structures to which certain proteins or molecules can bind. While some pockets are easily identifiable within a protein structure, others are not. Those hidden pockets, referred to as cryptic pockets, can provide new opportunities for drugs to bind to. The more pockets scientists and clinicians have to target with drugs, the more opportunities they have to control disease.
The research team identified new pockets using a Penn-designed neural network, called PocketMiner, which is artificial intelligence that predicts where cryptic pockets are likely to form from a single protein structure and learns from itself. Using PocketMiner—which was trained on simulations run on the world’s largest super computer—researchers simulated single protein structures and successfully predicted the locations of cryptic pockets in 35 cancer-related protein structures in thousands of areas of the body. These once-hidden targets, now identified, open up new approaches for potentially treating existing cancer.
What’s more, while successfully predicting the cryptic pockets, the method scientists used in this study was much faster than previous simulation or machine-learning methods. The network allows researchers to nearly instantaneously decide if a protein is likely to have cryptic pockets before investing in more expensive simulations or experiments to pursue a predicted pocket further.
“More than half of human proteins are considered undruggable due to an apparent lack of binding proteins in the snapshots we have,” said Gregory R. Bowman, PhD, a professor of Biochemistry and Biophysics and Bioengineering at Penn and the lead author of the study. “This PocketMiner research and other research like it not only predict druggable pockets in critical protein structures related to cancer but suggest most human proteins likely have druggable pockets, too. It’s a finding that offers hope to those with currently untreatable diseases.”
William Danon and Luka Yancopoulos pose in front of College Hall in April 2022. They are co-founders of Grapevine and the winners of the 2022 President’s Innovation Prize. (Photo: Eric Sucar)
In April 2022, three President’s Prize-winning teams were selected from an applicant pool of 71 people to develop projects that promote engagement and innovation. Each project received $100,000, as well as a $50,000 living stipend per team member.
The President’s Innovation Prize and President’s Engagement Prize winners included Grapevine, which aims to better connect buyers and suppliers to stabilize the medical supply chain market; IF Ventures, with its mission to scale impact by supporting college students with early-stage startup ideas that have measurable social and environmental impact; and Cosmic Writers, which organizes writing workshops to cultivate K-12 students to be better writers and communicators — and, therefore, better citizens.
“In less than a year, these three PIP and PEP prize-winning teams have already proven their commitment to making a difference in the world,” says President Liz Magill. “Their projects are ambitious and inspiring, and I am proud the University has been able to provide financial and networking support for these determined changemakers.”
After graduating in May 2022, Luka Yancopoulos, an Environmental Studies major and a Bioengineering major in the School of Engineering and Applied Science and William Danon, a History major, relocated to an office space in Westchester, New York, and got to work on a research and validation process — first, by spending a day at a Penn Medicine facility, Lancaster General Health, then by committing hundreds of hours to interviewing distributor and procurement teams alike, along with potential client companies. The mission, as any researcher knows, was to understand key pain points. They also onboarded veterans in logistics, technology, and payment security and processing while devising an organizational structure in which Yancopoulous leads on technology and design solutions while Danon interfaces with customers to know what needs remain unmet.
Grapevine soft launched in fall 2022 and, they say, has interfaced with 30 companies through its digital platform to facilitate sales among 40 suppliers, amounting to more than $20,000 in transactions. The appeal of the platform, they say, remains the concept of the “digital supply chain network,” which Yancopoulos says partners can use to connect with resellers, hospitals, distributors, and others to reduce the risk of supply chain disruption that is not just a product of the pandemic, he adds, but “forever ongoing.”
“It’s driven by the principle that together we’re stronger, and I mean that in every aspect of my life,” he says. “That people are stronger, and with Grapevine we work to [bolster] supply chains and increase the accessibility of health care products — together.”
Since winning the President’s Innovation Prize, they’ve focused on working with small- to medium-sized businesses — whether local clinics or high-quality, specialized resellers — that struggle to compete with or pay for traditional, large-scale distributors that are better-resourced or too expensive. It’s allowed them to also find new users, like health care-adjacent businesses including funeral homes and tattoo parlors.
Their current tagline: “Grow with us,” Danon says.
Watch a video overview of Grapevine’s progress since receiving the PIP prize and read more about the other PIP/PEP prize winners at Penn Today.
A new Penn Medicine preclinical study demonstrates a simultaneous ‘knockout’ of two inflammatory regulators boosts T cell expansion to attack solid tumors.
by Meagan Raeke
Image: Courtesy of Penn Medicine News
A new approach that delivers a “one-two punch” to help T cells attack solid tumors is the focus of a preclinical study by researchers from the Perelman School of Medicine. The findings, published in the Proceedings of the National Academy of Sciences, show that targeting two regulators that control gene functions related to inflammation led to at least 10 times greater T cell expansion in models, resulting in increased anti-tumor immune activity and durability.
“We want to unlock CAR T cell therapy for patients with solid tumors, which include the most commonly diagnosed cancer types,” says June, the new study’s senior author. “Our study shows that immune inflammatory regulator targeting is worth additional investigation to enhance T cell potency.”
One of the challenges for CAR T cell therapy in solid tumors is a phenomenon known as T cell exhaustion, where the persistent antigen exposure from the solid mass of tumor cells wears out the T cells to the point that they aren’t able to mount an anti-tumor response. Engineering already exhausted T cells from patients for CAR T cell therapy results in a less effective product because the T cells don’t multiply enough or remember their task as well.
Previous observational studies hinted at the inflammatory regulator Regnase-1 as a potential target to indirectly overcome the effects of T cell exhaustion because it can cause hyperinflammation when disrupted in T cells—reviving them to produce an anti-tumor response. The research team, including lead author David Mai, a bioengineering graduate student in the School of Engineering and Applied Science, and co-corresponding author Neil Sheppard, head of the CCI T Cell Engineering Lab, hypothesized that targeting the related, but independent Roquin-1 regulator at the same time could boost responses further.
“Each of these two regulatory genes has been implicated in restricting T cell inflammatory responses, but we found that disrupting them together produced much greater anti-cancer effects than disrupting them individually,” Mai says. “By building on previous research, we are starting to get closer to strategies that seem to be promising in the solid tumor context.”
A team of researchers led by the School of Arts & Science’s Wei Guo offers new insights into a mechanism that promotes tumor growth. “This information could be used to help clinicians diagnose cancers earlier in the future,” says Guo.
In many instances, the physical manifestation of cancers and the ways they are subsequently diagnosed is via a tumor, tissue masses of mutated cells and structures that grow excessively. One of the major mysteries in understanding what goes awry in cancers relates to the environments within which these structures grow, commonly known as the tumor microenvironment.
These microenvironments play a role in facilitating tumor survival, growth, and spread. Tumors can help generate their own infrastructure in the form of vasculature, immune cells, signaling molecules, and extracellular matrices (ECMs), three-dimensional networks of collagen-rich support scaffolding for a cell. ECMs also help regulate cellular communications, and in the tumor microenvironment ECMs can be a key promoter of tumor growth by providing structural support for cancerous cells and in modulating signaling pathways that promote growth.
Now, new research led by the School of Arts & Science’sWei Guo and published in the journal Nature Cell Biology has bridged the complex structural interactions within the tumor microenvironment to the signals that trigger tumor growth. The researchers studied cancerous liver cells grown on ECMs of varying stiffness and discovered that the stiffening associated with tumor growth can initiate a cascade that increases the production of small lipid-encapsulated vesicles known as exosomes.
“Think of these exosomes as packages that each cell couriers out, and, depending on the address, they get directed to other cells,” says Ravi Radhakrishnan, professor of bioengineering in the School of Engineering and Applied Science and a co-author of the paper.
“By recording the number of packages sent, the addresses on these packages, their contents, and most importantly, how they’re regulated and generated, we can better understand the relationship between a patient’s tumor microenvironment and their unique molecular signaling signatures, hinting at more robust personalized cancer therapies,” Radhakrishnan says.
While studying exosomes in relation to tumor growth and metastasis has been well-documented in recent years, researchers have mostly focused on cataloging their characteristics rather than investigating the many processes that govern the creation and shuttling of exosomes between cells. As members of Penn’s Physical Sciences Oncology Center (PSOC), Guo and Radhakrishnan have long collaborated on projects concerning tissue stiffness. For this paper, they sought to elucidate how stiffening promotes exosome trafficking in cancerous intracellular signaling.
“Our lab previously found that high stiffness promotes the secretion of exosomes,” says Di-Ao Liu, co-first author of the paper and a graduate student in the Guo Lab. “Now, we were able to model the stiffening processes through experiments and identify molecular pathways and protein networks that cause this, which better links ECM stiffening to cancerous signaling.”
Savan Patel, a fourth year Penn Bioengineering student, is one of 42 finalists competing for a 2023 Hertz Fellowship in applied science, mathematics, and engineering, one of the most prestigious Ph.D. fellowships in the United States. Chosen annually, the Hertz Fellowship is awarded to the nation’s most promising graduate students in science and technology.
“Since 1963, the Hertz Foundation has granted fellowships empowering the nation’s most promising young minds in science and technology. Hertz Fellows receive five years of funding valued at up to $250,000, which offers flexibility from the traditional constraints of graduate training and the independence needed to pursue research that best advances our security and economic vitality […]
Over the foundation’s 60-year history of awarding fellowships, more than 1200 Hertz Fellows have established a remarkable track record of accomplishments. Their ranks include two Nobel laureates; recipients of 10 Breakthrough Prizes and three MacArthur Foundation “genius awards”; and winners of the Turing Award, the Fields Medal, the National Medal of Technology, and the National Medal of Science. In addition, 50 are members of the National Academies of Sciences, Engineering and Medicine, and 34 are fellows of the American Association for the Advancement of Science. Hertz Fellows hold over 3,000 patents, have founded more than 375 companies and have created hundreds of thousands of science and technology jobs.”
Patel is studying Bioengineering and Finance in the Jerome Fisher Program in Management and Technology (M&T), an interdisciplinary dual degree program coordinated by Penn Engineering and the Wharton School of Business. He is currently a member of the lab of Michael J. Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering. Patel’s research interests lie at the interface of drug delivery and immunoengineering. His current project involves the use of modified cholesterol molecules to induce shifts in the biodistribution of ionizable lipid nanoparticles (LNPs). Following graduation, he intends to pursue a Ph.D. in bioengineering in which hopes to develop translatable immunotherapies and drug delivery platforms.
If chosen, the Hertz Fellowship will fund Patel’s graduate studies. Selected from over 750 applicants, Patel is one of fifteen undergraduates and one of two bioengineering students to make the final round of interviews. After a culminating round of interviews, the 2023 Class of Hertz Fellows will be announced in May.
Learn more about the Hertz Fellowship and read the full list of finalists here.
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.
Devin Carroll, a doctoral candidate in the School of Engineering and Applied Sciences, is designing a modular robot called StickBot, which may be adapted for rehabilitation use in global public health settings.
StickBot in walking mode, using the sticks as legs to propel itself across the table.
In late summer, just as the leaves were starting to crisp and curl in the heat, Devin Carroll walked out of his apartment, looked on the ground, and picked up a couple of sticks that he thought might work for his robot. About half an inch thick and the length of an adult hand, he stripped the three sticks of their bark and lashed them with string to StickBot, a modular robot composed of circuitry, actuators, a microcontroller, and a motor driver.
Controlling the robot using an app he designed, Carroll shows how StickBot can pivot from using the sticks as legs in “crawler mode,” to using them as arms. In “grasper mode,” the sticks are attached to a controller plate on one side to form a hinge joint while moving with their free end to hold a cup upright.
Rather than a static, singular invention, StickBot is an idea, a flexible system that can be reconfigured in a variety of ways. A modular robot, StickBot’s components can be added, adjusted, and discarded as needed.
This article features quotes from Michelle Johnson, Associate Professor in Physical Medicine and Rehabilitation in the Perelman School of Medicine and in Bioengineering in the School of Engineering and Applied Sciences, and Director of the Rehabilitation Robotics Lab.
