The effectiveness of CAR T cell therapy against a variety of cancers, including solid tumors, could be boosted greatly by using CRISPR-Cas9 technology to knock out the gene for CD5, a protein found on the surface of T cells, according to a preclinical study from investigators at the University of Pennsylvania’s Perelman School of Medicine and Abramson Cancer Center.
CAR T cells are T cells that have been engineered to attack specific targets found on cancer cells. They have had remarkable results in some patients with blood cancers. But they have not performed well against other cancers including solid-tumor cancers, such as pancreatic cancer, prostate cancer, and melanoma. Researchers have been searching for techniques to boost the effectiveness of CAR T cell therapy.
The study, published today in Science Immunology, suggests that knocking out CD5 could be a prime technique. Illuminating the protein’s previously murky role, the researchers found that it works as a powerful immune checkpoint, reining in T cell effectiveness. Removing it, they showed, dramatically enhanced CAR T cell anticancer activity in a variety of preclinical cancer models.
“We’ve discovered in preclinical models that CD5 deletion greatly enhances the function of CAR T cells against multiple cancers,” said senior author Marco Ruella, MD, an assistant professor of Hematology-Oncology, researcher with the Center for Cellular Immunotherapies and the scientific director of Penn Medicine’s Lymphoma Program. “The striking effects we observed across preclinical models suggest that CD5 knockout could be a general strategy for enhancing CAR T cell function.”
The study’s first author is Ruchi Patel, PhD, a recent graduate student from the Ruella Laboratory.
BE’s award-winning team, Epilog, at the 2024 Senior Design Awards.
How do you make robotics kits affordable for children in low-income countries? Speed up the manufacturing of organs-on-a-chip? Lower the environmental impact of condiments in restaurants?
If you’re a senior at Penn Engineering, the answer is to team up with your peers in the Senior Design Project Competition, which every year draws interdisciplinary groups from across the School’s six majors to solve real-world problems. Championed by the late Walter Korn (EE’57, GEE’68), a past president of the Engineering Alumni Society (EAS), Senior Design also invites alumni back to campus to evaluate the seniors’ year-long capstone projects.
Since the program started nearly two decades ago, hundreds of alumni have shared centuries’ worth of their collective experience with soon-to-be-minted graduates in the form of constructive feedback. “Senior Design is really one of the best days at Penn Engineering,” says Bradley Richards (C’92, LPS’17), Director of Alumni Relations, who manages the program. “Faculty advisors work with students all year long to bring out the best in each group’s efforts, and the results speak for themselves.”
This year, three student teams from each of Penn Engineering’s six departments — Bioengineering (BE), Chemical and Biomolecular Engineering (CBE), Computer and Information Science (CIS), Electrical and Systems Engineering (ESE), Materials Science and Engineering (MSE), and Mechanical Engineering and Applied Mechanics (MEAM) — presented their work to more than 60 alumni in person and online.
Judges’ Choice Award
The Judges’ Choice Award, which recognizes overall excellence, went to ESE’s VivoDisk, which developed a novel machine to manufacture organs-on-a-chip for Vivodyne, a startup launched by Dan Huh, Associate Professor in BE.
As one of the team members, Akash Chauhan (ENG’24), learned while interning for Vivodyne, assembling the stacks of organs-on-a-chip, which are collections of plastic plates containing cells that simulate organs for preclinical drug testing, is extremely finicky and time consuming.
By developing a machine that could automatically align the plates with high precision using computer vision and AI, the team reduced the disks’ manufacturing time and expense, leading Vivodyne to adopt the device for commercial use, accelerating the process of drug discovery. VivoDisk’s team members included Chauhan; Angela Rodriguez (ENG’24), Aliris Tang (ENG’24, W’24), Dagny Lott (ENG’24), Simone Kwee (ENG’24) and Vraj Satashia (ENG’24, GEN’25) and was advised by Sid Deliwala, Alfred Moore Senior Fellow and Director of Lab Programs in ESE, and Jan Van der Spiegel, Professor in ESE.
Technology and Innovation Award
One of the greatest challenges for children with epilepsy is status epilepticus, an abnormal type of long-lasting seizure that is hard to distinguish from typical seizures and that has a mortality rate of 30%. There is currently no way to perform a test for status epilepticus at home, meaning that children suspected of having the condition must be rushed to the hospital for an electroencephalogram.
Epilog, a team from BE, developed a novel, wearable headset that analyzes brainwaves to accurately determine whether or not a child suffering a seizure is actually suffering from status epilepticus. The team, composed of Rohan Chhaya (ENG’24, GEN’24), Carly Flynn (ENG’24), Elena Grajales (ENG’24), Priya Shah (ENG’24, GEN’25) and Doris Xu (ENG’24) and advised by Erin Berlew, Research Scientist in the Department of Orthopaedic Surgery and Lecturer in BE, carefully validated the device’s accuracy.
The judges recognized Epilog’s technological expertise, which ran the gamut from software to hardware, including a custom app to work with the device and carefully considered features like electrodes whose position can be adjusted to accommodate a child’s growth over time.
Neurological disorders such as epilepsy, Alzheimers, Parkinson’s and certain forms of dementia are the leading cause of disability and second-leading cause of disease worldwide. These disorders disproportionately affect low-resourced communities due to lack of access to specialized healthcare, and many of these complex diseases lack curative solutions. The need to address neurological disorders is high, yet current diagnostics and treatments are not effective for preventative or personalized care and are not accessible or affordable enough to meet the needs of more than 3 billion people living with neurological disorders.
Flavia Vitale, Associate Professor in Bioengineering in Penn Engineering and in Neurology in Penn Medicine, works to meet this need, developing accessible and affordable solutions for the diagnosis, treatment and rehabilitation of people with neurological disorders.
“I started my research career in biomedical engineering hoping to one day help humanity,” says Vitale, who is also a 2024 recipient of a National Science Foundation (NSF) CAREER Award for her work. “But it wasn’t until I gained a more diverse skill set during my doctoral and postdoctoral research across chemical engineering and materials science that I was able to do that in a real way.”
Vitale’s multidisciplinary skills are what allow her to develop devices that help people living with brain disorders. The CAREER Award is now helping her further apply those skills and actualize some of her first long-term research projects at Penn.
“This CAREER Award will support my lab’s current research in leveraging innovation in materials and fabrication approaches to develop devices that are able to interface with and control different chemical and electrical signals inside the brain,” she says.
Focused primarily on understanding the brain activity involved in epilepsy-induced seizures, Vitale aims to design and develop brain-interface devices to pinpoint and suppress uncontrolled brain activity to prevent seizures from happening. Her work will lead to revolutionary health care for the 30% of epilepsy patients whose conditions are drug resistant. Currently those patients either wait out the uncontrolled brain activity and oftentimes life-threatening convulsions, or hope to be eligible for invasive surgeries to remove the part of the brain where seizures originate or to implant the seizure-controlling devices that are currently available.
Bicontinuous materials, like this representation of a cube of gelatin and hyaluronic acid, have greater internal surface area, allowing cells to travel faster between two points. (Credit: Karen Xu)
One of the most important but least understood aspects of healing is cell migration, or the process of cells moving from one part of the body to another. “If you are an ambulance out in the woods,” says Karen Xu, an M.D/Ph.D. student in Medicine and Bioengineering, “and there are no paths for you to move forward, it will be a lot harder for you to get to a site that needs you.”
Earlier this year, Xu co-authored a paper in Nature Communications describing a new cue to help cells get to where they need to go: a material made chiefly of hyaluronic acid and gelatin, two gooey substances commonly found outside cells in joints and connective tissue.
“Hundreds of thousands of people tear their meniscus every year,” says Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery in Penn Medicine and Professor in Bioengineering at Penn Engineering and one of Xu’s advisors, as well as a senior author on the paper. “This material could potentially speed up their recovery.”
What makes the material — known as a hydrogel due to its blend of gelatinous matter and water — unique is that the combination of hyaluronic acid and gelatin forms a complex network of paths, providing cells many different ways to travel between two points.
This property is known as bicontinuity, and is exemplified by two discrete continuous phases that are each connected throughout the entire volume of the material (for example with a sponge, with phases of cellulose and air; in the hydrogel, this is comprised of gelatin and hyaluronic acid) resulting in a dizzying array of patterns that dramatically increase the surface area inside the material.
To test the hydrogel’s efficacy, Xu and her collaborators — including co-advisor Jason Burdick, formerly the Robert D. Bent Professor in Bioengineering at Penn Engineering and now the Bowman Endowed Professor at the University of Colorado Boulder, and the paper’s other senior author — first created several different versions of the hydrogel to find the sweet spot at which the constituents formed the bicontinuous structure and had the highest internal surface area. “We found that a precise combination of the various hydrogel components and control over their mixing was needed to form the bicontinuous structure,” says Burdick.
Team Current Care (Andrew Lee, Antranig Baghdassarian, Johnson Liu, Leah Lackey, Brianna Leung, and Justin Liu), took home the $3,000 Grand Prize in the Cornell Hackathon.
Brianna Leung, a rising senior majoring in Bioengineering and minoring in Neuroscience and Healthcare Management at the University of Pennsylvania, led a diverse team of student scientists and engineers to resounding success at the 2024 Cornell Health Tech Hackathon, where the team won the $3,000 Grand Prize.
Held in March 2024 on Cornell’s campus in New York City, the event brought together students from 29 different universities for a weekend of finding “hacks” to patient wellness and healthcare issues inspired by the theme of “patient safety.”
ADAPT members enjoy a pancake-making marathon in preparation for their pancake sale.
Leung serves as President of Penn Assistive Devices and Prosthetic Technologies (ADAPT), a medical-device project club whose members pursue personal projects, community partnerships and national design competitions. Penn ADAPT’s activities range from designing, building and improving assistive medical devices for conditions such as cerebral palsy and limb loss, to community engagement activities like their semesterly 3D-printed pancake sale.
In her role, Leung has increased the program’s hackathon participation to give club members greater exposure to fast-paced, competition-based design. She also leads the HMS School project, which develops and manufactures switch interfaces for children with cerebral palsy, enabling these students to interact with computers.
Leung’s passion for medical devices extends to her academic research. As a member of the robotics lab of Cynthia Sung, Gabel Family Term Assistant Professor in Mechanical Engineering and Applied Mechanics, Computer and Information Science, and Electrical and Systems Engineering, Leung characterizes origami patterns for energy-saving applications in the heart and in facial reconstruction. Leung has also served as Vice President External for the Penn Lions and Vice President of Member Engagement for the Wharton Undergraduate Healthcare Club, and belongs to the Phi Gamma Nu professional business fraternity.
ADAPT members working on medical devices.
For the Cornell Hackathon, Leung’s team developed a prototype for Current Care, a closed-loop device to prevent pressure ulcers through electrical muscle stimulation. Pressure ulcers, often called bed sores, result from prolonged pressure, which often occurs during extended hospitalization or in patients who are bedridden. This condition is exacerbated by understaffing and strained resources, and can create an extra burden on hospitals, patients and healthcare workers. The U.S. Department of Health and Human Services estimates that pressure ulcers cost the U.S. healthcare system approximately $9.1 billion to $11.6 billion per year.
Current Care is designed to deliver electrical stimulation, which increases blood flow to affected body parts. Conceptualizing and designing complex devices on short notice is the nature of a hackathon, so the team focused their efforts on creating proof-of-concept prototypes for all the different sensors required for the device, as well as providing the judges with on-screen read-outs to demonstrate the logic and hypothetical inputs for the device.
For their design, the team was awarded the $3,000 Grand Prize in the Cornell Hackathon. In addition to Leung, the team consisted of Johnson Liu (Cornell ECE & MSE’26); Antranig Baghdassarian (Cornell BME’27); Andrew Lee (Weill Cornell M.D.’25); Leah Lackey (Cornell ECE Ph.D.’28); and Justin Liu (Northeastern CS’27).
In choosing a project, Leung was inspired by her late grandmother’s experiences. “My role on the team largely consisted of coordinating and leading aspects of its development as needed. I also ultimately presented our idea to the judges,” she says. “This was actually all of my teammates’ first hackathon, so it was really exciting to serve a new role (considering it was actually only my second hackathon!). I had a lot of fun working with them, and we have actually been meeting regularly since the event to continue to work on the project. We had a range of expertise and experience on our team, and I deeply appreciate their hard work and enthusiasm for a project that means so much to me.”
Having found success at the Cornell hackathon, the team is discussing next steps for Current Care. “Our team is still very motivated to continue working on the project, and we’ve been speaking with professors across all of our schools to discuss feasibility and design plans moving forward,” says Leung.
Several other projects developed by Penn ADAPT members were recognized in the Cornell Hackathon:
ADAPT members and Hackathon participants, left to right: Brianna Leung, Rebecca Wang, Claire Zhang, Amy Luo, Mariam Rizvi, Natey Kim, Joe Kojima. Also in attendance but not pictured: Suhani Patel, Harita Trivedi, Dwight Koyner.
Claire Zhang, a sophomore studying Bioengineering and Biology in the VIPER program, was a member and presenter for team CEDAR (winner of Most Innovative/2nd Place), a portable ultrasound imaging device used to monitor carotid artery stenosis development in rural areas.
Natey Kim, a sophomore in Bioengineering, was a member and presenter for team HMSS (finalist), a low-cost digital solution for forecasting infections in hospitals.
Rebecca Wang, a sophomore in Bioengineering and Social Chair of Penn ADAPT, was a member of Team Femnostics (winner of Most Market Ready/4th Place) which developed QuickSense, an all-in-one diagnostic tool that streamlines testing for a handful of the most common vaginal disease infections simultaneously.
Mariam Rizvi, a sophomore in Computational Biology, was a member of team IPVision (winner of Most Potential Impact/5th Place), an application programming interface (or API) that integrates into electronic health records such as Epic, leveraging AI to detect intimate partner violence cases and provide personalized treatment in acute-care settings.
Suhani Patel and Dwight Koyner worked with team RealAIs, which developed a full-stack multi-platform application using React Native and Vertex AI on the Google Cloud Platform (GCP). Patel, a sophomore double majoring in Bioengineering and Computer and Information Science in Penn Engineering, serves as ADAPT’s treasurer, while Koyner is a first-year M&T student studying Business and Systems Engineering in Penn Engineering and Wharton.
Team Femnostics from left to right: Antonia Li, Bhavishya Agarwal, Urmila Sehrawat, Rebecca Wang, Justin Xiang, and Edward Kim.Team IPVision from left to right: Elizabeth Madamidola, Keshika Gopinathan, Emily L. Leventhal, Mariam Rizvi, Raquel Castromonte, and Lina ChihoubTeam Cedar from left to right: Claire Zhang, Ethan Tse, Danny Nguyen, Allen Dinh, and Reem UllayTeam RealAIs from left to right: Rishi Shah, Suhani Patel, Saanvi Mehra, Dwight Koyner, Chimdi Ejiogu, and Garrett Breslin
Learn more about Penn ADAPT here and follow their Instagram.
Read more about the 2024 Cornell Tech Hackathon in the Cornell Chronicle.
Leaders and faculty from Penn Medicine, including Kevin Mahoney, Carl June, John Wherry, and Mike Mitchell (pictured left to right), speak on stage during the Penn London symposium.
Sharing the exciting work happening at Penn with alumni, parents, and friends throughout the world is a priority for Interim President J. Larry Jameson.
Shortly after challenging the graduating Class of 2024 to “keep reinventing, learning, and engaging” he brought that same spirit to the Penn community in London. He met with leadership volunteers from the region and welcomed approximately 200 attendees to an academic symposium titled “Frontiers of Knowledge and Discovery: Leading in a Changing World.”
Kevin Mahoney, CEO of the University of Pennsylvania Health System, moderated the first panel, on the genesis of breakthroughs. “When our faculty explain how landmark achievements like new fields of science or first-in-class cancer therapies come about, they never fail to emphasize how collaboration turns expertise into progress,” he said. “Hearing Mike Mitchell, John Wherry, and Carl June speak made plain how our brilliant, interconnected Penn faculty work together on one campus with results that are changing our world.”
Vijay Kumar, the Nemirovsky Family Dean of Penn Engineering, shared Mahoney’s perspective on collaboration—with a twist. “Non-engineers can be mystified, if not intimidated, by the complexities of the work we do,” he explained. “When a faculty member breaks down a project and talks it through, step by step, the engineering concepts become so much more understandable and relatable.” Kumar moderated a session with Dan Rader and Rene Vidal that focused on the increasing and powerful synergies among data science and AI, medical research, and clinical practice
Michael Mitchell is Associate Professor in Bioengineering. Read more stories featuring Mitchell in the BE Blog.
Carl June is Richard W. Vague Professor in Immunotherapy in the Perelman School of Medicine and is a member of the Penn Bioengineering Graduate Group. Read more stories featuring June in the BE Blog.
Lipid nanoparticles present one of the most advanced drug delivery platforms to shuttle promising therapeutics such as mRNA but are limited by the time it takes to synthesize cationic lipids, a key component. Now, Michael Mitchell and his team at the School of Engineering and Applied Science have developed a faster way to make cationic lipids that are also more versatile, able to carry different kinds of treatments to target specific organs. (Image: iStock / Dr_Microbe)
Imagine a scenario where a skilled hacker must upload critical software to update a central server and thwart a potentially lethal virus from wreaking havoc across a vast computer network. The programmer, armed with the lifesaving code, must navigate through treacherous territory teeming with adversaries, and success hinges on promptly getting a safe, stealthy delivery vehicle that can place the hacker exactly where they need to be.
In the context of modern medicine, messenger RNA (mRNA) serves as the hacker, carrying genetic instructions to produce specific proteins within cells that can induce desired immune responses or sequester maladaptive cellular elements. Lipid nanoparticles (LNPs) are the stealthy delivery vehicles that transport these fragile mRNA molecules through the bloodstream to their target cells, overcoming the body’s defenses to deliver their payload safely and efficiently.
However, much like building an advanced stealth vehicle, the synthesis of cationic lipids—a type of lipid molecule that’s positively charged and a key component of LNPs—is often a time-consuming process, involving multiple steps of chemical synthesis and purification.
Now, Michael Mitchell and a team at the University of Pennsylvania have addressed this challenge with a novel approach that leverages a compound library fabrication technique known as “click-like chemistry” to create LNPs in a single, simple step. Their findings, published in the journal Nature Chemistry, show that this method not only speeds up the synthesis process but also presents a way to equip these delivery vehicles with a “GPS” to better target specific organs such as the liver, lungs, and spleen, potentially opening new avenues for treating a range of diseases that arise in these organs.
“We’ve developed what we call an amidine-incorporated degradable (AID) lipid, a uniquely structured biodegradable molecule,” Mitchell says. “Think of it as an easy-to-build custom mRNA vehicle with a body kit that informs its navigation system. By adjusting its shape and degradability, we can enhance mRNA delivery into cells in a safe manner. By adjusting the amount of the AID lipid that we incorporate into the LNP, we can also guide it to different organs in the body, much like programming different destinations into a GPS.”
First author Xuexiang Han, a former postdoctoral researcher in the Mitchell Lab, explains that their new approach allows the rapid creation of diverse lipid structures in just an hour, compared to the weekslong process traditionally required.
Congratulations to the fifteen Bioengineering students to receive 2024 National Science Foundation Graduate Research Fellowship Program (NSF GRFP) fellowships. The prestigious NSF GRFP program recognizes and supports outstanding graduate students in NSF-supported fields. The recipients were selected from a highly-competitive, nationwide pool. Further information about the program can be found on the NSF website.
The following Ph.D. students in Bioengineering received awards:
Congratulations to Alison Pouch, Assistant Professor in Bioengineering in the School of Engineering and Applied Science, and in Radiology in the Perelman School of Medicine, on winning a 2024 Cardiac Center Innovation Award for scientific research from the Children’s Hospital of Philadelphia (CHOP)’s Philly Spin-In. Pouch’s study, titled “Systemic Semilunar Valve Mechanics and Simulated Repair in Congenital Heart Disease,” is a collaboration with Matthew Jolley, Assistant Professor of Anesthesiology and Critical Care at CHOP:
“Through biomechanical assessment, Drs. Matthew Jolley and Alison Pouch are leading an interdisciplinary CHOP-Penn team that plans to determine why current approaches to systemic semilunar valve (SSV) repair fail. They will also investigate methods to design improved repairs before going to the operating room by using computational simulation to iteratively optimize repair.
‘We believe that understanding biomechanics of abnormal SSVs and explorations of simulated repair will markedly improve our ability to characterize, risk stratify, and surgically treat SSV dysfunction, thereby improving long-term outcomes and quality of life in patients with SSV dysfunction,’ Dr. Jolley said.”
Pouch’s lab focuses on 3D/4D segmentation and modeling of heart valves in echocardiographic images with applications to surgical treatment of valvular regurgitation as part of the Penn Image Computing and Science Laboratory.
The instrument imaging team, from left: Philadelphia Orchestra bassist Duane Rosengard; Peter Noël, PhD, director of CT Research at the Perelman School of Medicine; luthier Zachary S. Martin; Leening Liu, a PhD student in Noël’s Laboratory of Advanced Computed Tomography Imaging; and Mark Kindig.
When you’re an expert in medical CT imaging, two things are bound to happen, says Peter Noël, PhD, associate professor of Radiology and director of CT Research at the Perelman School of Medicine. One: You develop an insatiable curiosity about the inner workings of all kinds of objects, including those unrelated to your research. And two: Both colleagues and complete strangers will ask for your help in imaging a wide variety of unexpected items.
Over the course of his career, in between managing his own research projects, Noël has imaged diverse objects ranging from animal skulls to tree samples from a German forest, all in the name of furthering scientific knowledge. But none has intrigued him as much as his current extracurricular project: the first known attempt to perform CT imaging of some of the world’s finest string basses.
The goal is to crack the code on what makes a world-class instrument. This knowledge could both increase the ability to better care for masterworks built between the 17th and 19th centuries, as well as providing insights into refining the building of new ones, including possibly shifting from older, scarcer European wood to the use of sustainably harvested U.S. wood.
That’s why Noël and Leening Liu, a PhD student in Noël’s Laboratory of Advanced Computed Tomography Imaging, have found themselves volunteering to run the basses through a Penn CT scanner occasionally, when they’re not developing next-generation CT technology.
“We always learn something out of projects like this … the more appealing part is that medical research can also be applied to non-medical things,” Noël said. “We have the opportunity to take what we learn in medicine and use it for something else—in this case, moving the arts forward.”
Leening Liu is a Ph.D. student in Bioengineering. She is a member of the Laboratory for Advanced Tomography Imaging (LACTI) with research interests including clinical applications of spectral CT and spectral CT thermometry.
