Showing Up for Penn in London

by Laura Bellet

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 MitchellJohn 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

Read the full story in the Penn Giving website.

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.

Alison Pouch Wins 2024 Cardiac Center Innovation Award

Alison Pouch

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.

Read the full awards announcement in the CHOP Cornerstone Blog.

How to Learn About a World-class Double Bass? Give it a CT

by Darcy Lewis  

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.”

Read the full story in Penn Medicine News.

Peter Noël is Assistant Professor of Radiology in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group.

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.

Largest-Ever Antibiotic Discovery Effort Uses AI to Uncover Potential Cures in Microbial Dark Matter

by Eric Horvath

Credit: Georgina Joyce

Almost a century ago, the discovery of antibiotics like penicillin revolutionized medicine by harnessing the natural bacteria-killing abilities of microbes. Today, a new study co-led by researchers at the Perelman School of Medicine at the University of Pennsylvania suggests that natural-product antibiotic discovery is about to accelerate into a new era, powered by artificial intelligence (AI).

The study, published in Cell, the researchers used a form of AI called machine learning to search for antibiotics in a vast dataset containing the recorded genomes of tens of thousands of bacteria and other primitive organisms. This unprecedented effort yielded nearly one million potential antibiotic compounds, with dozens showing promising activity in initial tests against disease-causing bacteria.

“AI in antibiotic discovery is now a reality and has significantly accelerated our ability to discover new candidate drugs. What once took years can now be achieved in hours using computers” said study co-senior author César de la Fuente, PhD, a Presidential Assistant Professor in Psychiatry, Microbiology, Chemistry, Chemical and Biomolecular Engineering, and Bioengineering.

Nature has always been a good place to look for new medicines, especially antibiotics. Bacteria, ubiquitous on our planet, have evolved numerous antibacterial defenses, often in the form of short proteins (“peptides”) that can disrupt bacterial cell membranes and other critical structures. While the discovery of penicillin and other natural-product-derived antibiotics revolutionized medicine, the growing threat of antibiotic resistance has underscored the urgent need for new antimicrobial compounds.

In recent years, de la Fuente and colleagues have pioneered AI-powered searches for antimicrobials. They have identified preclinical candidates in the genomes of contemporary humans, extinct Neanderthals and Denisovans, woolly mammoths, and hundreds of other organisms. One of the lab’s primary goals is to mine the world’s biological information for useful molecules, including antibiotics.

Read the full story in Penn Medicine News.

How “Invitations” from Penn Medicine Restored Mammogram Completion Rates

by Frank Otto

The first few waves of COVID-19 slowed life across the United States, affecting everything from attending school to eating out for dinner and going on vacation. Segments of health care were also affected: Services that were not considered immediately crucial to fighting the virus were slowed or stopped during the pandemic’s first wave.  

But once Penn Medicine invited patients back to resume normal health care—including preventive care, like screenings for disease—there was some lag in numbers. 

“As we opened up to routine outpatient care, screening rates for situations when patients didn’t have symptoms were not returning back to normal,” said Mitchell Schnall, MD, PhD, FACR, a professor of Radiology, now the senior vice president for Data and Technology Solutions at Penn Medicine, and then the head of a team focused on the “resurgence” efforts to ease patients back into outpatient care. “Although a short delay in health screening is likely not going to cause long-term health problems, we were concerned whether screening rates would stay lower and lead to a long-term impact.”  

Read the full story in Penn Medicine News.

Mitchell Schnall is a member of the Penn Bioengineering Graduate Group.

Different Brain Structures in Females Lead to More Severe Cognitive Deficits After Concussion Than Males

by Kelsey Geesler

Top: Axons in female and male subject brains Bottom: damaged axons in male and female brains after injury (Credit: Penn Medicine)

Important brain structures that are key for signaling in the brain are narrower and less dense in females, and more likely to be damaged by brain injuries, such as concussion. Long-term cognitive deficits occur when the signals between brain structures weaken due to the injury. The structural differences in male and female brains might explain why females are more prone to concussions and experience longer recovery from the injury than their male counterparts, according to a preclinical study led by the Perelman School of Medicine at the University of Pennsylvania, published this week in Acta Neuropathologica.

Each year, approximately 50 million individuals worldwide suffer a concussion, also referred to as mild traumatic brain injury (TBI). However, there is nothing “mild” about this condition for the more than 15 percent of individuals who suffer persisting cognitive dysfunction, which includes difficulty concentrating, learning and remembering new information, and making decisions.

Although males make up the majority of emergency department visits for concussion, this has been primarily attributed to their greater exposure to activities with a risk of head impacts compared to females. In contrast, it has recently been observed that female athletes have a higher rate of concussion and appear to have worse outcomes than their male counterparts participating in the same sport.

“Clinicians have observed for a long time that females suffer from concussion at higher rates than males in the same sports, and that they take longer to recover cognitive function, but couldn’t explain the underlying mechanisms of this phenomenon,” said senior author Douglas Smith, MD, a professor of Neurosurgery and director of Penn’s Center for Brain Injury and Repair. “The variances in brain structures of females and males not only illuminate why this disparity exists, but also exposes biomarkers, such as axon protein fragments, that can be measured in the blood to determine injury severity, monitor recovery, and eventually help identify and develop treatments that help patients repair these damaged structures and restore cognitive function.”

Read the full story in Penn Medicine News.

Douglas H. Smith is a member of the Penn Bioengineering Graduate Group.

The CiPD Partners with the Mack Institute for Innovation and Management to Develop Tooth-Brushing Robots

by Melissa Pappas

Left to right: Hong-Huy Tran, Chrissie Jaruchotiratanasakul, Manali Mahajan (Photo Courtesy of CiPD)

The Center for Innovation and Precision Dentistry (CiPD), a collaboration between Penn Engineering and Penn Dental Medicine, has partnered with Wharton’s Mack Institute for Innovation Management on a research project which brings robotics to healthcare. More specifically, this project will explore potential uses of nanorobot technology for oral health care. The interdisciplinary partnership brings together three students from different Penn programs to study the commercialization of a new technology that detects and removes harmful dental plaque.

“Our main goal is to bring together dental medicine and engineering for out-of-the-box solutions to address unresolved problems we face in oral health care,” says Hyun (Michel) Koo, Co-Founding Director of CiPD and Professor of Orthodontics. “We are focused on affordable solutions and truly disruptive technologies, which at the same time are feasible and translatable.”

Read the full story in Penn Engineering Today.

Michel Koo is a member of the Penn Bioengineering Graduate Group. Read more stories featuring Koo in the BE Blog.

To learn more about this interdisciplinary research, please visit CiPD.

This press release has been adapted from the original published by the Mack Institute for Innovation Management.

Study Reveals Inequities in Access to Transformative CAR T Cell Therapy

Image: iStock/PeopleImages

Patients being treated for B-cell non-Hodgkin’s Lymphoma (NHL) who are part of minority populations may not have equal access to cutting-edge CAR T cell therapies, according to a new analysis led by researchers from the Perelman School of Medicine and published in NEJM Evidence.

CAR T cell therapy is a personalized form of cancer therapy that was pioneered at Penn Medicine and has brought hope to thousands of patients who had otherwise run out of treatment options. Six different CAR T cell therapies have been approved since 2017 for a variety of blood cancers, including B-cell NHL that has relapsed or stopped responding to treatment. Image: iStock/PeopleImages

“CAR T cell therapy represents a major leap forward for blood cancer treatment, with many patients living longer than ever before, but its true promise can only be realized if every patient in need has access to these therapies,” says lead author Guido Ghilardi, a postdoctoral fellow in the laboratory of senior author Marco Ruella, an assistant professor of hematology-oncology and scientific director of the Lymphoma Program. “From the scientific perspective, we’re constantly working in the laboratory to make CAR T cell therapy work better, but we also want to make sure that when a groundbreaking treatment like this becomes available, it reaches all patients who might be able to benefit.”

Read the full story in Penn Medicine News.

Marco Ruella is a member of the Penn Bioengineering Graduate Group. Read more stories featuring Ruella in the BE Blog.

Scientists Discover a Key Quality-Control Mechanism in DNA Replication

by Meagan Raeke

Illustration of the 55LCC complex. (Image: Courtesy of Cameron Baines/Phospho Biomedical Animation)

When cells in the human body divide, they must first make accurate copies of their DNA. The DNA replication exercise is one of the most important processes in all living organisms and is fraught with risks of mutation, which can lead to cell death or cancer. Now, findings from biologists from the Perelman School of Medicine and from the University of Leeds have identified a multiprotein “machine” in cells that helps govern the pausing or stopping of DNA replication to ensure its smooth progress. Illustration of the 55LCC complex. (Image: Courtesy of Cameron Baines/Phospho Biomedical Animation)

The discovery, published in Cell, advances the understanding of DNA replication, helps explain a puzzling set of genetic diseases, and could inform the development of future treatments for neurologic and developmental disorders.

“We’ve found what appears to be a critical quality-control mechanism in cells,” says senior co-corresponding author Roger Greenberg, the J. Samuel Staub, M.D. Professor in the department of Cancer Biology, director of the Penn Center for Genome Integrity, and director of basic science at the Basser Center for BRCA at Penn Medicine. “Trillions of cells in our body divide every single day, and this requires accurate replication of our genomes. Our work describes a new mechanism that regulates protein stability in replicating DNA. We now know a bit more about an important step in this complex biological process.”

Read the full story at Penn Medicine News.

Greenberg is a member of the Penn Bioengineering Graduate Group.

Kyle Vining Earns Hartwell Foundation Award to Study Childhood Leukemia

Kyle Vining, D.D.S., Ph.D.

Kyle Vining, Assistant Professor in Preventive and Restorative Sciences in Penn Dental Medicine and in Materials Science and Engineering in Penn Engineering, has received an Individual Biomedical Research Award from The Hartwell Foundation to explore a novel approach to improving treatment for childhood leukemia. Vining is among ten researchers representing eight institutions selected as a 2023 Hartwell Foundation awardee. Vining is also a member of the Penn Bioengineering Graduate Group.

“The proposed studies lay the foundation to make a major scientific impact in the childhood leukemia field and ultimately improve outcomes for children,” says Vining.

Read the full story at Penn Dental Medicine.

Read more stories featuring Vining in the BE Blog.