Category: faculty

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Yale Cohen and Douglas Smith Awarded 2020 Penn Medicine Awards of Excellence

Yale Cohen, Ph.D.
Douglas H. Smith, M.D.

The Perelman School of Medicine has announced the winners of the 2020 Penn Medicine Awards of Excellence. The Office of the Dean says:

“These awardees exemplify our profession’s highest values of scholarship, teaching, innovation, commitment to service, leadership, professionalism and dedication to patient care. They epitomize the preeminence and impact we all strive to achieve. The awardees range from those at the beginning of their highly promising careers to those whose distinguished work has spanned decades.

Each recipient was chosen by a committee of distinguished faculty from the Perelman School of Medicine or the University of Pennsylvania. The contributions of these clinicians and scientists exemplify the outstanding quality of patient care, mentoring, research, and teaching of our world-class faculty.”

Two faculty members affiliated with Penn Bioengineering are among this year’s recipients.

Yale Cohen, PhD, Professor of Otorhinolaryngology with secondary appointments in Neuroscience and Bioengineering, is the recipient of the Jane M. Glick Graduate Student Teaching Award. Cohen is an alumnus of the Penn Bioengineering doctoral program and is currently the department’s Graduate Chair.

“Dr. Cohen’s commitment to educating and training the next generation of scientists exemplifies the type of scientist and educator that Jane Glick represented. His students value his highly engaging and supportive approach to teaching, praising his enthusiasm, energy, honesty, and compassion.”

Douglas H. Smith, MD, Robert A. Groff Endowed Professor of Research and Teaching in Neurosurgery and member of the Penn Bioengineering Graduate Group, is the recipient of this year’s William Osler Patient Oriented Research Award:

“Dr. Smith is the foremost authority on diffuse axonal injury (DAI) as the unifying hypothesis behind the short- and long-term consequences of concussion.  After realizing early in his career that concussion, or mild traumatic brain injury (TBI), was a much more serious event than broadly appreciated, Dr. Smith and his team have used computer biomechanical modeling, in vitro and in vivo testing in parallel with seminal human studies to elucidate mechanisms of concussion.”

Read the full story in Penn Medicine Communications.

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Through Brain Imaging Analysis in Rats, Penn Researchers Show Potential to Predict Whether Pain Will be Acute or Persistent

Beth Winkelstein, Megan Sperry, and Eric Granquist

Pain may be a universal experience, but what actually causes that experience within our brains is still poorly understood. Pain often continues long after the relevant receptors in the body have stopped being stimulated and can persist even after those receptors cease to exist, as is the case with “phantom limb” pain.

The exact experience an individual will have after a painful incident comes down to the complex, variable connections formed between several different parts of the brain. The inability to predict how those connections will form and evolve can make pain management a tricky, frustrating endeavor for both healthcare providers and patients.

Now, a team of Penn researchers has shown a way to make such predictions from the pattern of neural connections that begin to take shape soon after the first onset of pain. Though their study was conducted in rats, it suggests that similar brain imaging techniques could be used to guide treatment decisions in humans, such as which individuals are most likely to benefit from different drugs or therapies.

The study, published in the journal Pain, was led by Beth Winkelstein, Eduardo D. Glandt President’s Distinguished Professor in Penn Engineering’s Department of Bioengineering and Deputy Provost of the University of Pennsylvania, along with Megan Sperry, then a graduate student in her lab. Eric Granquist, Director of the Center for Temporomandibular Joint Disease at the Hospital of the University of Pennsylvania in the Department of Oral & Maxillofacial Surgery, and assistant professor of Oral & Maxillofacial Surgery in Penn’s School of Dental Medicine, also contributed to the research.

“Our findings provide the first evidence that brain networks differ between acute and persistent pain states, even before those different groups of rats actually show different pain symptoms,” says Winkelstein.

Read the full story at Penn Engineering Today. Media contact Evan Lerner.

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Ravi Radhakrishnan Adapts Multiscale Modeling Course

 

Ravi Radhakrishnan, PhD

Ravi Radhakrishnan, Professor and Chair of the Department of Bioengineering and Professor in Chemical and Biomolecular Engineering, is among the many faculty who quickly adapted their courses to an online format in the wake of the COVID-19 pandemic. Now, a recent publication in the American Institute of Chemical Engineers (AIChE) Journal reflects one of these revamped courses. The course BE 559: “Multiscale Modeling of Chemical and Biological Systems” provides theoretical, conceptual, and hands-on modeling experience on three different length and time scales: (1) electronic structure (A, ps); (2) molecular mechanics (100A, ns); and (3) deterministic and stochastic approaches for microscale systems (um, sec). During the course, students gained hands-on experience in running codes on real applications together with the following theoretical formalisms: molecular dynamics, Monte Carlo, free energy methods, deterministic and stochastic modeling. The transition to the online format was greatly facilitated by a grant from the Extreme Science and Engineering Discovery Environment (XSEDE) which provided cloud and supercomputing resources to the students facilitating the computational laboratory experience. Radhakrishnan’s article, “A survey of multiscale modeling: Foundations, historical milestones, current status, and future prospects,” reviews the foundations, historical developments, and current paradigms in multiscale modeling (MSM).

Radhakrishnan aspires to modernize computational science, integrating Multiscale Modeling and Data Science for Biological and Biomedical Science & Engineering. His team does so by integrating multiphysics modeling, computing, data science to tackle applications. The integrative approach is pictorially depicted here in terms of modeling different length and timescales using techniques such as molecular dynamics of atomistic systems, Brownian dynamics of coarse-grained systems, and field equations governing continuum scales of macroscopic systems.

Read the full article in the AIChE Journal: https://doi.org/10.1002/aic.17026

Funding source: National Institutes of Health, Grant/Award Number: CA227550

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Engineering Bacteria-Killing Molecules from Wasp Venom

César de la Fuente, PhD

César de la Fuente a Presidential Assistant Professor in the Perelman School of Medicine’s departments of Psychiatry and Microbiology and Engineering’s department of Bioengineering, has racked up accolades for his innovative, computational approach to discovering new antibiotics.

Now, in his most recent study, de la Fuente has shown how these vital drugs might be derived from wasp venom.

The study, published in The Proceedings of the National Academy of Sciences, involved altering a highly toxic small protein from a common Asian wasp species, Vespula lewisii, the Korean yellow-jacket wasp. The alterations enhanced the molecule’s ability to kill bacterial cells while greatly reducing its ability to harm human cells. In animal models, de la Fuente and his colleagues showed that this family of new antimicrobial molecules made with these alterations could protect mice from otherwise lethal bacterial infections.

There is an urgent need for new drug treatments for bacterial infections, as many circulating bacterial species have developed a resistance to older drugs. The U.S. Centers for Disease Control & Prevention has estimated that each year nearly three million Americans are infected with antibiotic-resistant microbes and more than 35,000 die of them. Globally the problem is even worse: Sepsis, an often-fatal inflammatory syndrome triggered by extensive bacterial infection, is thought to have accounted for about one in five deaths around the world as recently as 2017.

“New antibiotics are urgently needed to treat the ever-increasing number of drug-resistant infections, and venoms are an untapped source of novel potential drugs. We think that venom-derived molecules such as the ones we engineered in this study are going to be a valuable source of new antibiotics,” says de la Fuente.

De la Fuente and his team started with a small protein, or “peptide,” called mastoparan-L, a key ingredient in the venom of Vespula lewisii wasps. Mastoparan-L-containing venom is usually not dangerous to humans in the small doses delivered by wasp stings, but it is quite toxic. It destroys red blood cells, and triggers a type of allergic/inflammatory reaction that in susceptible individuals can lead to a fatal syndrome called anaphylaxis—in which blood pressure drops and breathing becomes difficult or impossible.

Mastoparan-L (mast-L) also is known for its moderate toxicity to bacterial species, making it a potential starting point for engineering new antibiotics. But there are still some unknowns, including how to enhance its anti-bacterial properties, and how to make it safe for humans.

Continue reading at Penn Medicine News.

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Brian Litt Receives NIH Pioneer Award to Develop Implantable Neurodevices

Brian Litt, MD

Brian Litt, professor in Engineering’s Department of Bioengineering and the Perelman School of Medicine’s departments of Neurology and Neurosurgery, has received a five-year, $5.6 million Pioneer Award from the National Institutes of Health, which will support his research on implantable devices for monitoring, recording and responding to neural activity.

The Pioneer Award is part of the agency’s High-Risk, High-Reward Research Program honoring exceptionally creative scientists. It challenges investigators to pursue new research directions and develop groundbreaking, high-impact approaches to a broad area of biomedical or behavioral science. Litt’s neurodevice research represents a new frontier in addressing a wide variety of neurological conditions.

In epilepsy, for example, these devices would predict and prevent seizures; in Parkinson’s patients, implants will measure and communicate with patients to improve mobility, reduce tremor and enhance responsiveness. Other implants might improve hearing or psychiatric symptoms by querying patient perceptions, feelings, and altering stimulation patterns algorithmically to improve them

Continue reading about Litt’s Pioneer Award at Penn Medicine News.

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New Research from Penn Engineering and MIT Shows How Nanoparticles Can Turn Off Genes in Bone Marrow

Michael Mitchell
Michael Mitchell, PhD

by Evan Lerner

Using specialized nanoparticles, researchers from Penn Engineering and the Massachusetts Institute of Technology (MIT) have developed a way to turn off specific genes in cells of bone marrow, which play an important role in producing blood cells. These particles could be tailored to help treat heart disease or to boost the yield of stem cells in patients who need stem cell transplants.

This type of genetic therapy, known as RNA interference, is usually difficult to target to organs other than the liver, where nanoparticles would tend to accumulate. The researchers were able to modify their particles in such a way that they would accumulate in the cells found in the bone marrow.

In a recent Nature Biomedical Engineering study, conducted in mice, the researchers showed that they could use this approach to improve recovery after a heart attack by inhibiting the release of bone marrow blood cells that promote inflammation and contribute to heart disease.

“If we can get these particles to hit other organs of interest, there could be a broader range of disease applications to explore, and one that we were really interested in in this paper was the bone marrow. The bone marrow is a site for hematopoiesis of blood cells, and these give rise to a whole lineage of cells that contribute to various types of diseases,” says Michael Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, one of the lead authors of the study.

Marvin Krohn-Grimberghe, a cardiologist at the Freiburg University Heart Center in Germany, and Maximilian Schloss, a research fellow at Massachusetts General Hospital (MGH), are also lead authors on the paper, which appears today in Nature Biomedical Engineering. The paper’s senior authors are Daniel Anderson, a professor of Chemical Engineering at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and Matthias Nahrendorf, a professor of Radiology at MGH.

Mitchell’s expertise is in the design of nanoparticles and other drug delivery vehicles, engineering them to cross biological barriers that normally block foreign agents. In 2018, he received the NIH Director’s New Innovator Award to support research on delivering therapeutics to bone marrow, a key component of this new study.

The researchers have shown they can deliver nanoparticles to the bone marrow, influencing their function with RNA silencing. At top right, the bone marrow is not yet treated with particles that turn off a gene called SDF1. At bottom right, the number of neutrophils (blue) decreases, indicating that they have been released from bone marrow after treatment. At left, treatment with a control nanoparticle does not affect the number of neutrophils before and after treatment.

Read the full story at Penn Engineering Today.

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In Memoriam: David Geselowitz, 1930-2020

David Geselowitz

Penn Engineering mourns the death of our former colleague Dr. David Geselowitz, who died on August 22, 2020. The Penn Engineering and Penn State communities have lost a brilliant scientist and researcher, and an extraordinary teacher, mentor and friend.

Dr. Geselowitz was born in Philadelphia in 1930, and graduated from the University of Pennsylvania, where he received his bachelor’s, master’s and doctoral degrees in Electrical Engineering in 1951, 1954 and 1958, respectively. As the top student in his undergraduate class, he received the Atwater Kent Award.

After receiving his Ph.D., he joined the faculty of the University of Pennsylvania and subsequently founded Penn’s doctoral program in biomedical engineering. In 1971, he moved to Penn State University to implement a graduate program in bioengineering.

Dr. Geselowitz was known for his contributions to the theory of the electrocardiogram (EKG) and the development of the artificial heart. As noted by the late Dr. Herman Schwan, “David was the best man I had met in electrocardiography work. The National Academy of Engineering recognized him for that work. He became a leader in the country in the field.”

For more on the life of Dr. Geselowitz, please see the tribute from his longtime colleagues at Penn State: https://news.engr.psu.edu/2020/geselowitz-david-obituary.aspx

This story originally appeared in Penn Engineering News.

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A potential cause of CAR T side effects, and a path forward

Single cell sequencing aided researchers in identifying a previously undiscovered molecule in the brain.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized treatment of leukemia, lymphoma, and multiple myeloma. But some people who have received this treatment experience neurotoxicity, or damage to the brain or nervous system.

New research from a team led by Avery Posey, an assistant professor of systems pharmacology and translational therapeutics in the Perelman School of Medicine, provides evidence that this side effect may owe to a molecule in the brain that scientists previously didn’t know was there.

The work, published in the journal Cell, revealed that the protein CD19 is present in brain cells that protect the blood-brain barrier. Prior to the finding, scientists believed CD19 was only expressed on B cells, and the protein served as a target for certain forms of CAR-T therapy. The discovery may chart a path forward for new strategies to effectively treat cancer while sparing the brain.

“The next question is,” says Posey, “can we identify a better target for eliminating B cell related malignancies other than CD19, or can we engineer around this brain cell expression of CD19 and build a CAR T cell that makes decisions based on the type of cell it encounters—for instance, CAR T cells that kill the B cells they encounter, but spare the CD19 positive brain cells?”

Read more at Penn Medicine News. Avery Posey is a member of the Department of Bioengineering Graduate Group.

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César de la Fuente on AIChE’s 35 Under 35 List

César de la Fuente, PhD

César de la Fuente, Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering, was named one of the American Institute of Chemical Engineers’ (AIChE) 35 members under 35 for 2020.

“The AIChE 35 Under 35 Award was founded to recognize young chemical engineers who have achieved greatness in their fields,” reads the 2020 award announcement. “The winners are a group of driven, engaged, and socially active professionals, representing the breadth and diversity that chemical engineering exemplifies.”

De la Fuente was named in the list’s “Bioengineering” category for his his lab’s work in machine biology. Their goal is to develop computer-made tools and medicines that will combat antibiotic resistance. De la Fuente has already been featured on several other young innovators lists, including MIT Technology Review’s 35 under 35 and GEN’s Top 10 under 40, both in 2019. His research in antibiotic resistance has been profiled in Penn Today and Penn Engineering Today, and he was recently awarded Penn Health-Tech’s inaugural NEMO Prize for his proposal to develop paper-based COVID diagnostic system that could capture viral particles on a person’s breath.

In addition to being named on the 2020 list, the honorees will receive a $500 prize and will be celebrated at the 2020 AIChE Annual Meeting this November.

Learn more about de la Fuente’s pioneering research on his lab website.

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‘The Self-Organized Movement to Create an Inclusive Computational Neuroscience School’

When the COVID-19 pandemic began taking hold in the United States, one of the first “superspreader” events was an academic conference. Such conferences have long been a primary way for researchers to share new findings and launch collaborations, but with thousands of people from around the world, indoors and in close proximity, it quickly became clear that the traditional format for these events would need to radically change.

Konrad Kording
Konrad Kording

Konrad Kording, a Penn Integrates Knowledge Professor with appointments in the departments of Bioengineering and Computer and Information Science in Penn Engineering and the Department of Neuroscience at Penn’s Perelman School of Medicine, was ahead of the curve on this shift. With the issues of prohibitive costs and environmental impact of travel in mind, Kording had already started brainstorming ways of reinventing the traditional conference format when the pandemic made it a necessity.

The resulting event, Neuromatch, involved algorithmically analyzing participants’ work in order to connect researchers who might not otherwise meet. Building on the success of that “unconference,” Kording and his colleagues launched the Neuromatch Academy, a free-ranging online summer school organized around the same principles.

Ashley Juavinett writing for The Simons Collaboration on the Global Brain, recently dug into how Neuromatch was able to pull together 1,750 students from 70 countries in a matter of months:

Kording already had experience quickly pulling together online events. Early in the pandemic, together with Dan Goodman, Titipat Achakulvisut and Brad Wyble, he developed an online ‘unconference,’ which featured both lectures and a virtual networking component designed to mimic the in-person interactions that make conferences so valuable. (For more, see “Designing a Virtual Neuroscience Conference.”) Soon after, they decided to spin that success into a full-fledged summer school offering live lectures with top computational neuroscientists, guided coding exercises to teach mathematical approaches to neural modeling and analysis, and community support from mentors and teaching assistants (TAs).

The result was a summer school with well-designed content, a diverse student body, including participants from U.S.-sanctioned Iran, and a determined group of organizers who managed to pull off the most inclusive computational neuroscience school yet. NMA now has its eye on a future with even broader representation across countries, languages and skill levels. This year has been incredibly difficult for many, but NMA has provided an important precedent for how to collaborate across, and even dismantle, all sorts of barriers.

Continue reading “The Self-Organized Movement to Create an Inclusive Computational Neuroscience School” at The Simons Collaboration on the Global Brain.

Originally posted on the SEAS blog. Media contact Evan Lerner.