René Vidal, at the podium, introduces the event “ChatGPT turns one: How is generative AI reshaping science?” Bhuvnesh Jain, left at the table, moderated the discussion with Sudeep Bhatia, Konrad Kording, Andrew Zahrt, and Nick Pangakis.
As a neuroscientist surveying the landscape of generative AI—artificial intelligence capable of generating text, images, or other media—Konrad Kording cites two potential directions forward: One is the “weird future” of political use and manipulation, and the other is the “power tool direction,” where people use ChatGPT to get information as they would use a drill to build furniture.
“I’m not sure which of those two directions we’re going but I think a lot of the AI people are working to move us into the power tool direction,” says Kording, a Penn Integrates Knowledge (PIK) University professor with appointments in the Perelman School of Medicine and School of Engineering and Applied Science. Reflecting on how generative AI is shifting the paradigm of science as a discipline, Kording said he thinks “it will push science as a whole into a much more collaborative direction,” though he has concerns about ChatGPT’s blind spots.
Kording joined three University of Pennsylvania researchers from the chemistry, political science, and psychology departments sharing their perspectives in the recent panel “ChatGPT turns one: How is generative AI reshaping science?” PIK Professor René Vidal opened the event, which was hosted by the School of Arts & Sciences’ Data Driven Discovery Initiative (DDDI), and Bhuvnesh Jain, physics and astronomy professor and co-faculty director of DDDI, moderated the discussion.
“Generative AI is moving so rapidly that even if it’s a snapshot, it will be very interesting for all of us to get that snapshot from these wonderful experts,” Jain said. OpenAI launched ChatGPT, a large language model (LLM)-based chatbot, on Nov. 30, 2022, and it rapidly ascended to ubiquity in news reports, faculty discussions, and research papers. Colin Twomey, interim executive director of DDDI, told Penn Today that it’s an open question as to how it will change the landscape of scientific research, and the` idea of the event was to solicit colleagues’ opinions on interesting directions in their fields.
Konrad Paul Kording is Nathan Francis Mossell University Professor in Bioengineering and Computer and Information Science in Penn Engineering and in Neuroscience in the Perelman School of Medicine.
Vaccines for COVID-19 were the first time that mRNA technology was used to address a worldwide health challenge. The Penn Medicine scientists behind that technology were awarded the 2023 Nobel Prize in Physiology or Medicine. Next come all the rest of the potential new treatments made possible by their discoveries.
But curbing the pandemic was only the beginning of the potential for this Nobel Prize-winning technology.
These biomedical innovations from Penn Medicine in using mRNA represent a multi-use tool, not just a treatment for a single disease. The technology’s potential is virtually unlimited; if researchers know the sequence of a particular protein they want to create or replace, it should be possible to target a specific disease. Through the Penn Institute for RNA Innovation led by Weissman, who is the Roberts Family Professor of Vaccine Research in Penn’s Perelman School of Medicine, researchers are working to ensure this limitless potential meets the world’s most challenging and important needs.
Infectious Diseases and Beyond
Just consider some of the many projects Weissman’s lab is partnering in: “We’re working on malaria with people across the U.S. and in Africa,” Weissman said. “We’re working on leptospirosis with people in Southeast Asia. We’re working on vaccines for peanut allergies. We’re working on vaccines for autoimmunity. And all of this is through collaboration.”
Clinical trials are underway for the new malaria vaccine, as well as for a Penn-developed mRNA vaccine for genital herpes and one that aims to protect against all varieties of coronaviruses. Trials should begin soon for vaccines for norovirus and the bacterium C. difficile.
Single-Injection Gene Therapies for Sickle Cell and Heart Disease
Drew Weissman, MD, PhD, is a co-winner of the 2023 Nobel Prize in Physiology or Medicine for discoveries with mRNA.
The Weissman lab is working to deploy mRNA technology as an accessible gene therapy for sickle cell anemia, a devastating and painful genetic disease that affects about 20 million people around the world. About 300,000 babies are born each year with the condition, mainly in sub-Saharan Africa. Weissman’s team has developed technology to efficiently deliver modified mRNA to bone marrow stem cells, instructing red blood cells to produce normal hemoglobin instead of the malformed “sickle” version that causes the illness. Conventional gene therapies are complex and expensive treatments, but the mRNA gene therapy could be a simple, one-time intravenous injection to cure the disease. Such a treatment would have applications to many other congenital gene defects in blood and stem cells.
In another new program, Penn Medicine researchers have found a way to target the muscle cells of the heart. This gene therapy method developed by Weissman’s team, together with Vlad Muzykantov, MD, PhD, the Founders Professor in Nanoparticle Research could potentially repair the heart or increase blood flow to the heart, noninvasively, after a heart attack or to correct a genetic deficiency in the heart. “That is important because heart disease is the number one killer in the U.S. and in the world,” Weissman said. “Drugs for heart disease aren’t specific for the heart. And when you’re trying to treat a myocardial infarction or cardiomyopathy or other genetic deficiencies in the heart, it’s very difficult, because you can’t deliver to the heart.”
Weissman’s team also is partnering on programs for neurodevelopmental diseases and for neurodegenerative diseases, to replace genes or deliver therapeutic proteins that will treat and potentially cure these diseases.
“The potential is unbelievable,” Weissman said. “We haven’t thought of everything that can be done.”
Vladimir R. Muzykantov is Founders Professor in Nanoparticle Research in the Department of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine. He is a member of the Penn Bioengineering Graduate Group.
Daeyeon Lee (left), Oren Friedman (center) and Sergei Vinogradov (right)
Each year, the Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize, funded by Penn Health-Tech, awards $80,000 to a collaborative team of researchers from the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science for early-stage, interdisciplinary ideas.
This year, the NEMO Prize has been awarded to Penn Engineering’s Daeyeon Lee, Russel Pearce and Elizabeth Crimian Heuer Professor in Chemical and Biomolecular Engineering, Oren Friedman, Associate Professor of Clinical Otorhinolaryngology in the Perelman School of Medicine, and Sergei Vinogradov, Professor in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Chemistry in the School of Arts & Sciences. Together, they are developing a new therapy that improves the survival and success of soft-tissue grafts used in reconstructive surgery.
More than one million people receive soft-tissue reconstructive surgery for reasons such as tissue trauma, cancer or birth defects. Autologous tissue transplants are those where cells and tissue such as fat, skin or cartilage are moved from one part of a patient’s body to another. As the tissue comes from the patient, there is little risk of transplant rejection. However, nearly one in four autologous transplants fail due to tissue hypoxia, or lack of oxygen. When transplants fail the only corrective option is more surgery. Many techniques have been proposed and even carried out to help oxygenate soft tissue before it is transplanted to avoid failures, but current solutions are time consuming and expensive. Some even have negative side effects. A new therapy to help oxygenate tissue quickly, safely and cost-effectively would not only increase successful outcomes of reconstructive surgery, but could be widely applied to other medical challenges.
The therapy proposed by this year’s NEMO Prize recipients is a conglomerate or polymer of microparticles that can encapsulate oxygen and disperse it in sustainable and controlled doses to specific locations over periods of time up to 72 hours. This gradual release of oxygen into the tissue from the time it is transplanted to the time it functionally reconnects to the body’s vascular system is essential to keeping the tissue alive.
“The microparticle design consists of an oxygenated core encapsulated in a polymer shell that enables the sustained release of oxygen from the particle,” says Lee. “The polymer composition and thickness can be controlled to optimize the release rate, making it adaptable to the needs of the hypoxic tissue.”
These life-saving particles are designed to be integrated into the tissue before transplantation. However, because they exist on the microscale, they can also be applied as a topical cream or injected into tissue after transplantation.
“Because the microparticles are applied directly into tissues topically or by interstitial injection (rather than being administered intravenously), they surpass the need for vascular channels to reach the hypoxic tissue,” says Friedman. “Their micron-scale size combined with their interstitial administration, minimizes the probability of diffusion away from the injury site or uptake into the circulatory system. The polymers we plan to use are FDA approved for sustained-release drug delivery, biocompatible and biodegrade within weeks in the body, presenting minimal risk of side effects.”
The research team is currently testing their technology in fat cells. Fat is an ideal first application because it is minimally invasive as an injectable filler, making it versatile in remodeling scars and healing injury sites. It is also the soft tissue type most prone to hypoxia during transplant surgeries, increasing the urgency for oxygenation therapy in this particular tissue type.
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.
Raj, who also holds an appointment in Genetics in the Perelman School of Medicine, is a pioneer in the burgeoning field of single-cell engineering and biology. Powered by innovative techniques he has developed for molecular profiling of single cells, his scientific discoveries range from the molecular underpinnings of cellular variability to the behavior of single cells across biology, including in diseases such as cancer.
Raj will deliver the 2023-24 Heilmeier Lecture at Penn Engineering during the spring 2024 semester.
This story originally appeared in Penn Engineering Today.
NAM, founded in 1970, is an independent organization of professionals that advises the entire scientific community on critical health care issues. Each year, NAM chooses up to 10 new ELHM Scholars who are early-to-mid-career professionals from a wide range of health-related fields, including biomedical engineering, internal medicine, psychiatry, radiology and journalism to serve a three-year term.
“We are delighted that Dr. de la Fuente is receiving recognition from the National Academy of Medicine for his breakthrough contributions and exceptional leadership in the life sciences,” says Vijay Kumar, Nemirovsky Family Dean of Penn Engineering. “His pioneering work using computers to accelerate antibiotic discovery is extraordinary. We proudly celebrate his selection as part of this outstanding group of scholars.”
Michel Koo of the School of Dental Medicine and David Cormode of the Perelman School of Medicine and the School of Engineering and Applied Science led a team of researchers that uncovered a way to combine two FDA-approved treatments to treat tooth decay that taps into the blend’s bacteria-killing capabilities without disrupting the mouth’s microbiome. (Image: iStock / Alex Sholom)
The sting of a toothache or the discovery of a cavity is a universal dread. Dental caries, more commonly known as tooth decay, is an insidious adversary, taking a toll on millions of mouths worldwide. Caries can lead to pain, tooth loss, infection, and, in severe cases, even death.
While fluoride-based treatments have long been the gold standard in dentistry, this singular approach is now dated and has limited effect. Current treatments do not sufficiently control biofilm—the main culprit behind dental caries—and prevent enamel demineralization at the same time. This dual dilemma becomes particularly pronounced in high-risk populations where the onset of the disease can be both rapid and severe.
“Traditional treatments often come short in managing the complex biofilm environment in the mouth,” Koo, senior co-author on the study, says. “Our combined treatment not only amplifies the effectiveness of each agent but does so with a lower dosage, hinting at a potentially revolutionary method for caries prevention in high-risk individuals.”
David Cormode is an associate professor of radiology and bioengineering with appointments in Penn’s Perelman School of Medicine and School of Engineering and Applied Science.
Other authors are Yue Huang, Nil Kanatha Pandey, Shrey Shah, and Jessica C. Hsu of Penn’s Perelman School of Medicine; Yuan Liu, Aurea Simon-Soro, Zhi Ren, Zhenting Xiaang, Dongyeop Kim, Tatsuro Ito, Min Jun Oh, and Yong Li of Penn’s School of Dental Medicine; Paul. J Smeets, Sarah Boyer, Xingchen Zhao, and Derk Joester of Northwestern University; and Domenick T. Zero of Indiana University.
The work was supported by the National Institute of Health (grants R01-DE025848 and TL1TR001423 and awards S10OD026871 and R90DE031532) and the National Science Foundation (awards ECCS-2025633 and DMR-1720139).
Microwell device with a solution in the reservoir (Image: Courtesy of David E. Reynolds)
Akin to the packages sent from one person to another via an elaborate postal system, cells send tiny parcels that bear contents and packaging material that serve key purposes: To protect the contents from the outside world and to make sure it gets to the right place via a label with an address.
These packages are known as extracellular vesicles (EVs)—lipid-bound molecules that serve a variety of regulatory and maintenance functions throughout the body. They assist in the removal of unwanted materials within the cell, and they transport proteins, aid in DNA and RNA transfer, and promote tumorigeneses in cancerous cells.
Given their myriad roles, EVs have taken center stage for many researchers in the biomedical space as they have the potential to improve current methods of disease detection and treatment. The main challenge, however, is accurately identifying the molecular contents of EVs while also characterizing the EVs, which, unlike other cellular components that are more homogenous, have more heterogeneity.
Now, a team of researchers at the University of Pennsylvania has developed a novel platform, droplet-free double digital assay, for not only profiling individual EVs but also accurately discerning their molecular contents. The researchers took the digital assay, which quantifies the contents of a molecule via binary metric—a 1 corresponds to the presence of a molecule and a zero to the lack thereof—and applies it to the EV. The work is published in Advanced Science.
The team was led by Jina Ko, an assistant professor with appointments in the School of Engineering and Applied Science and Perelman School of Medicine. “Our method allows for highly accurate quantification of the individual molecules inside an EV,” Ko says . “This opens up many doors in the realm of early disease detection and treatment.”
The researchers first compartmentalized individual EVs utilizing a microwell approach to isolate the EVs. Next, they captured individual molecules within the EVs and amplified the signal for clarity. The team then was able to determine the expression levels of pivotal EV biomarkers with remarkable precision via fluorescence.
Jina Ko is an assistant professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine and an assistant professor in the Department of Bioengineering in the School of Engineering and Applied Science at the University of Pennsylvania.
David Reynolds is a Ph.D. candidate in the Department of Bioengineering in Penn Engineering.
Other authors include, Menghan Pan, George Galanis, Yoon Ho Roh, Renee-Tyler T. Morales, Shailesh Senthil Kumar, and Su-Jin Heo of the Department of Bioengineering at Penn Engineering; Jingbo Yang and Xiaowei Xu of the Department of Pathology and Laboratory Medicine at Penn Medicine; and Wei Guo of the Department of Biology in the School of Arts & Sciences at Penn.
The research was supported by the National Institutes of Health: grants R00CA256353, R35 GM141832, and CA174523 (SPORE).
Breaking the code of the immune system could provide a new fundamental way of understanding, treating, and preventing every type of disease. Penn Medicine is investing in key discoveries about immunity and immune system function, and building infrastructure, to make that bold idea a reality.
This grandfather lives with primary progressive multiple sclerosis (MS), an autoimmune disorder that he controls with a medicine that depletes his body of the type of immune cells that make antibodies. So while he has completed his COVID-19 vaccine course, his immune system function isn’t very strong—and the invitation has arrived at a time when COVID-19 is still spreading rapidly.
You can imagine the scene as an older gentleman lifts a thick, creamy envelope from his mailbox, seeing his own name written in richly scripted lettering. He beams with pride and gratitude at the sight of his granddaughter’s wedding invitation. Yet his next thought is a sober and serious one. Would he be taking his life in his hands by attending the ceremony?
“In the past, all we could do was [measure] the antibody response,” says Amit Bar-Or, the Melissa and Paul Anderson President’s Distinguished Professor in Neurology at the Perelman School of Medicine, and chief of the Multiple Sclerosis division. “If that person didn’t have a good antibody response, which is likely because of the treatment they’re on, we’d shrug our shoulders and say, ‘Maybe you shouldn’t go because we don’t know if you’re protected.’”
Today, though, Bar-Or can take a deeper dive into his patients’ individual immune systems to give them far more nuanced recommendations. A clinical test for immune cells produced in response to the COVID-19 vaccine or to the SARS-CoV-2 virus itself—not just antibodies—was one of the first applied clinical initiatives of a major new Immune Health® project at Penn Medicine. Doctors were able to order this test and receive actionable answers through the Penn Medicine electronic health record for patients like the grandfather with MS.
“With a simple test and an algorithm we can have a very different discussion,” Bar-Or says. A test result showing low T cells, for instance, would tell Bar-Or his patient may get a meaningful jolt in immunity from a vaccine booster, while low antibody levels would suggest passive antibody therapy is more helpful. Or, the test might show his body is already well primed to protect him, making it reasonably safe to attend the wedding.
This COVID-19 immunity test is only the beginning.
Physicians and scientists at Penn Medicine are imagining a future where patients can get a precise picture of their immune systems’ activity to guide treatment decisions. They are working to bring the idea of Immune Health to life as a new area of medicine. In labs, in complex data models, and in the clinic, they are beginning to make sense out of the depth and breadth of the immune system’s millions of as-yet-undeciphered signals to improve health and treat illnesses of all types.
Penn Medicine registered the trademark for the term “Immune Health” in recognition of the potential impact of this research area and its likelihood to draw non-academic partners as collaborators in its growth. Today, at the south end of Penn’s medical campus, seven stories of research space are being added atop an office building at 3600 Civic Center Blvd., including three floors dedicated to Immune Health, autoimmunity, and immunology research.
The concept behind the whole project, says E. John Wherry, director of Penn Medicine’s Institute for Immunology and Immune Health (I3H), “is to listen to the immune system, to profile the immune system, and use those individual patient immune fingerprints to diagnose and treat diseases as diverse as immune-related diseases, cancer, cardiovascular disease, Alzheimer’s, and many others.”
The challenge is vast. Each person’s immune system is far more complex than antibodies and T cells alone. The immune system is made of multiple interwoven layers of complex defenders—from our skin and mucous membranes to microscopic memory B cells that never forget a childhood infection—meant to fortify our bodies from germs and disease. It is a sophisticated system that learns and adapts over our lifetimes in numerous ways, and it also falters and fails in some ways we understand and others that remain mysterious. And each person’s intricate internal battlefield is in some way unique.
The immune system is not just a set of defensive barricades, either. It’s also a potential source of deep insight about a person’s physiological functioning and responses to medical treatments.
“The immune system is sensing and keeping track of basically all tissues and all cells in our body all the time,” Wherry says. “It is surveying the body trying to clean up any invaders and restore homeostasis by maintaining good health.”
“Our goal is to essentially break the code of the immune system,” says Jonathan Epstein, executive vice dean of the Perelman School of Medicine and chief scientific officer at Penn Medicine. “By doing so, we believe we will be able to determine your state of health and your response to therapies in essentially every human disease.”
Jina Ko (left) and Kevin Johnson (right), both from the School of Engineering and the Perelman School of Medicine with appointments in Bioengineering, have received the National Institute of Health Director’s Award to support their “highly innovative and broadly impactful” research projects through the High-Risk, High-Reward program.
The National Institutes of Health (NIH) has awarded grants to three researchers from the University of Pennsylvania through the NIH Common Fund’s High-Risk, High-Reward Research program. The research of Kevin B. Johnson, Jina Ko, and Sheila Shanmugan will be supported through the program, which funds “highly innovative and broadly impactful” biomedical or behavioral research by exceptionally creative scientists.
The High-Risk, High-Reward Research program catalyzes scientific discovery by supporting highly innovative research proposals that, due to their inherent risk, may struggle in the traditional peer-review process despite their transformative potential. Program applicants are encouraged to think “outside the box” and pursue trail-blazing ideas in any area of research relevant to the NIH’s mission to advance knowledge and enhance health.
Two Penn Bioengineering faculty, Johnson and Ko, are among 85 recipients for 2023.
Johnson, the David L. Cohen University Professor of Pediatrics, is a Penn Integrates Knowledge University Professor who holds appointments in the Department of Computer and Information Science in the School of Engineering and Applied Science and the Department of Biostatistics, Epidemiology, and Informatics in the Perelman School of Medicine. He also holds secondary appointments in Bioengineering, Pediatrics, and in the Annenberg School for Communication. He is widely known for his work with e-prescribing and computer-based documentation and, more recently, work communicating science to lay audiences, which includes a documentary about health-information exchange. Johnson has authored more than 150 publications and was elected to the American College of Medical Informatics, Academic Pediatric Society, National Academy of Medicine, International Association of Health Science Informatics, and American Institute for Medical and Biological Engineering.
Ko is an assistant professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine and Department of Bioengineering in the School of Engineering and Applied Science. She focuses on developing single molecule detection from single extracellular vesicles and multiplexed molecular profiling to better diagnose diseases and monitor treatment efficacy. Ko earned her Ph.D. in bioengineering at Penn in 2018, during which time she developed machine learning-based microchip diagnostics that can detect blood-based biomarkers to diagnose pancreatic cancer and traumatic brain injury. For her postdoctoral training, she worked at the Massachusetts General Hospital and the Wyss Institute at Harvard University as a Schmidt Science Fellow and a NIH K99/R00 award recipient. Ko developed new methods to profile single cells and single extracellular vesicles with high throughput and multiplexing.
In an era peppered by breathless discussions about artificial intelligence—pro and con—it makes sense to feel uncertain, or at least want to slow down and get a better grasp of where this is all headed. Trusting machines to do things typically reserved for humans is a little fantastical, historically reserved for science fiction rather than science.
Not so much for César de la Fuente, PhD, the Presidential Assistant Professor in Psychiatry, Microbiology, Chemical and Biomolecular Engineering, and Bioengineering in Penn’s Perelman School of Medicine and School of Engineering and Applied Science. Driven by his transdisciplinary background, de la Fuente leads the Machine Biology Group at Penn: aimed at harnessing machines to drive biological and medical advances.
“Biology is complexity, right? You need chemistry, you need mathematics, physics and computer science, and principles and concepts from all these different areas, to try to begin to understand the complexity of biology,” he said. “That’s how I became a scientist.”
