Tag: Perelman

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2023 Solomon R. Pollack Awards for Excellence in Graduate Bioengineering Research

The Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research is given annually to the most deserving Bioengineering graduate students who have successfully completed research that is original and recognized as being at the forefront of their field. This year, the Department of Bioengineering at the University of Pennsylvania recognizes the stellar work of four graduate students in Bioengineering.

Margaret Billingsley

Dissertation: “Ionizable Lipid Nanoparticles for mRNA CAR T Cell Engineering”

Maggie Billingsley

Margaret earned a bachelor’s degree in Biomedical Engineering from the University of Delaware where she conducted research in the Day Lab on the use of antibody-coated gold nanoparticles for the detection of circulating tumor cells. She conducted doctoral research in the lab of Michael J. Mitchell, J. and Peter Skirkanich Assistant Professor in Bioengineering. After defending her thesis at Penn in 2022, Margaret began postdoctoral training at the Massachusetts Institute of Technology (MIT) in the Hammond Lab where she is investigating the design and application of polymeric nanoparticles for combination therapies in ovarian cancer. She plans to use these experiences to continue a research career focused on drug delivery systems.

“Maggie was an absolutely prolific Ph.D. student in my lab, who pioneered the development of new mRNA lipid nanoparticle technology to engineer the immune system to target and kill tumor cells,” says Mitchell. “Maggie is incredibly well deserving of this honor, and I am so excited to see what she accomplishes next as a Postdoctoral Fellow at MIT and ultimately as a professor running her own independent laboratory at a top academic institution.”

Victoria Muir

Dissertation: “Designing Hyaluronic Acid Granular Hydrogels for Biomaterials Applications”

Victoria Muir

Victoria is currently a Princeton University Presidential Postdoctoral Research Fellow in the lab of Sujit S. Datta, where she studies microbial community behavior in 3D environments. She obtained her Ph.D. in 2022 as an NSF Graduate Research Fellow at Penn Bioengineering under the advisement of Jason A. Burdick, Adjunct Professor in Bioengineering at Penn and Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado, Boulder. She received a B.ChE. in Chemical Engineering from the University of Delaware in 2018 as a Eugene DuPont Scholar. Outside of research, Victoria is highly active in volunteer and leadership roles within the American Institute of Chemical Engineers (AIChE), currently serving as Past Chair of the Young Professionals Community and a member of the Career and Education Operating Council (CEOC). Victoria’s career aspiration is to become a professor of chemical engineering and to lead a research program at the interaction of biomaterials, soft matter, and microbiology.

“Victoria was a fantastic Ph.D. student,” says Burdick. “She worked on important projects related to granular materials from the fundamentals to applications in tissue repair. She was also a leader in outreach activities, a great mentor to numerous undergraduates, and is already interviewing towards an independent academic position.”

Sadhana Ravikumar 

Dissertation: “Characterizing Medial Temporal Lobe Neurodegeneration Due to Tau Pathology in Alzheimer’s Disease Using Postmortem Imaging”

Sadhana Ravikumar

Sadhana completed her B.S. in Electrical Engineering at the University of Cape Town, South Africa in 2014 and her M.S. in Biomedical Engineering from Carnegie Mellon University in 2017. Outside of the lab, she enjoys spending time in nature and exploring restaurants in Philadelphia with friends. She focused her doctoral work on the development of computational image analysis techniques applied to ex vivo human brain imaging data in the Penn Image Computing and Science Laboratory of Paul Yushkevich, Professor of Radiology at the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group. She hopes to continue working at the intersection of machine learning and biomedical imaging to advance personalized healthcare and drug development.

“Dr. Sadhana Ravikumar’s Ph.D. work is a tour de force that combines novel methodological contributions crafted to address the challenge of anatomical variability in ultra-high resolution ex vivo human brain MRI with new clinical knowledge on the contributions of molecular pathology to neurodegeneration in Alzheimer’s disease,” says Yushkevich. “I am thrilled that this excellent contribution, as well as Sadhana’s professionalism and commitment to mentorship, have been recognized through the Sol Pollack award.”

Hannah Zlotnick

Dissertation: “Remote Force Guided Assembly of Complex Orthopaedic Tissues”

Hannah Zlotnick

Hannah was a Ph.D. candidate in the lab of Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and in Bioengineering. She successfully defended her thesis and graduated in August 2022. During her Ph.D., Hannah advanced the state-of-the-art in articular cartilage repair by harnessing remote fields, such as magnetism and gravity. Using these non-invasive forces, she was able to control cell positioning within engineered tissues, similar to the cell patterns within native cartilage, and enhance the integration between cartilage and bone. Her work could be used in many tissue engineering applications to recreate complex tissues and tissue interfaces. Hannah earned a B.S. in Biological Engineering from the Massachusetts Institute of Technology (MIT) in 2017 during which time she was also a member of the women’s varsity soccer team. At Penn, Hannah was also involved in the Graduate Association of Bioengineers (GABE) intramurals & leadership, and helped jumpstart the McKay DEI committee. Since completing her Ph.D., Hannah has begun her postdoctoral research as a Schmidt Science Fellow in Jason Burdick’s lab at the University of Colorado Boulder where she looks to improve in vitro disease models for osteoarthritis.

“Hannah was an outstanding graduate student, embodying all that is amazing about Penn BE – smart, driven, inventive and outstanding in every way,” says Mauck. “ I can’t wait to see where she goes and what she accomplishes!”

Congratulations to our four amazing 2023 Sol Pollack Award winners!

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Puneeth Guruprasad Wins 2023 Penn Prize for Excellence in Teaching by Graduate Students

Front, from left to right: Lucy Andersen, Vice Provost for Education Karen Detlefsen, Derek Yang, Ann Ho, and Arianna James. Back, from left to right: Ritesh Isuri, Adiwid (Boom) Devahastin Na Ayudhya, Oualid Merzouga, and Puneeth Guruprasad.

Ten winners of the 2023 Penn Prize for Excellence in Teaching by Graduate Students were announced at a ceremony held April 13 at the Graduate Student Center. The recipients, who represented five of Penn’s 12 schools, were recognized among a pool of 44 Ph.D. candidates and master’s students nominated primarily by undergraduates—a quality unique to and cherished about this Prize.

“It’s a particularly authentic expression of gratitude from undergraduates, and that’s really the pleasure [of presenting these awards],” says Vice Provost for Education Karen Detlefsen, who was present to announce the winners and award them with a certificate. (They also receive a monetary award.) “I’m so proud of our students: Our undergraduates, for taking the time to recognize what it is our graduate students contribute to the student body, and the graduate students who are contributing to the life of the University.

“Students are the lifeblood of the University and without them, we wouldn’t be here.”

The Prize began in the 1999-2000 academic year under former Penn President Judith Rodin. It was spearheaded by then-doctoral-candidate Eric Eisenstein and has been issued every year since. Nominations for the Prize often mention how graduate teaching assistants were able to take a complex subject and make it relatable or craft a course like philosophy or mathematics into an enjoyable—even highly anticipated—experience for students.

“Many nominations show how much students value a TA or a graduate instructor of record who shows that they care for their learning and for them as people, and who makes themself readily available to assist,” says Ian Petrie, director of graduate student programming for the Center for Teaching and Learning, who organizes the selection committee for the Prize. “Typically, however, committee members are also interested in seeing nominations that really point to how a graduate student instructor taught or gave feedback—not just how responsive they were to emails or how many office hours they had.”

He also emphasizes that many winners this year were not just teachers, but mentors—often helping undergraduates or new graduate students navigate not only the course but also Penn as an institution.

Puneeth Guruprasad

One of the winners, Puneeth Guruprasad, hails from Penn Bioengineering. Guruprasad is a fourth-year Ph.D. student in Bioengineering who conducts research in the lab of Marco Ruella, Assistant Professor of Medicine in the Division of Hematology/Oncology in the Perelman School of Medicine. Ruella is also a member of the Center for Cellular Immunotherapies (CCI) and the Penn Bioengineering Graduate Group.

Guruprasad studies mechanisms of resistance to chimeric antigen receptor (CAR) T cell therapy for cancer. He has served as a teaching assistant for five semesters: three for Intro to Biotransport Processes (BE 3500) taught by Alex Hughes, Assistant Professor in Bioengineering, and two for Cellular Engineering (BE 3060), taught by Daniel Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and in Chemical and Biomolecular Engineering. Both courses are a part of the core curriculum for undergraduate bioengineering students. His doctoral thesis focuses on how a specific interaction between CAR T cells and tumor cells limits their function across a range of cancers.

“I make myself approachable outside the classroom, and I think that’s one aspect of being a TA: having responsibilities that extend beyond the classroom,” says Guruprasad. “Dozens of times, I’ve spoken to students over coffee, or over some lunch, about what direction they want to take in their life, what they want to do outside of the course, and give them my two cents of advice. I try to individualize.”

This post was adapted from an original story by Brandon Baker in Penn Today. Read the full story and list of 2023 winners here.

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Carl H. June, MD, FAACR, Honored with 2023 AACR Award for Lifetime Achievement in Cancer Research

Carl June, MD

 The American Association for Cancer Research (AACR), the largest cancer research organization in the country and based in Philadelphia, will bestow its 2023 Award for Lifetime Achievement in Cancer Research to Carl June, Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine at Penn Medicine. June is also Director of the Center for Cellular Immunotherapies, Director of the Parker Institute for Cancer Immunotherapy, and member of the Penn Bioengineering Graduate Group. He is recognized for his groundbreaking work in developing the first gene-editing cell therapy for cancer and for his pioneering work with CAR T cell therapy.

Read the press release on the AACR website.

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Novel Tools for the Treatment and Diagnosis of Epilepsy

by Nathi Magubane

A neurologist examines an encephalogram of a patient’s brain.
Throughout his career, Brian Litt has fabricated tools that support international collaboration, produced findings that have led to significant breakthroughs, and mentored the next generation of researchers tackling neurological disorders. (Image: iStock Photo/Alona Siniehina)

When Brian Litt of the Perelman School of Medicine and School of Engineering and Applied Science began treating patients as a neurologist, he found that the therapies and treatments for epilepsy were mostly reliant on traditional pharmacological interventions, which had limited success in changing the course of the disease.

People with epilepsy are often prescribed anti-seizure medications, and, while they are effective for many, about 30% of patients still continue to experience seizures. Litt sought new ways to offer patients better treatment options by investigating a class of devices that electronically stimulate cells in the brain to modulate activity known as neurostimulation devices.

Litt’s research on implantable neurostimulation devices has led to significant breakthroughs in the technology and has broadened scientists’ understanding of the brain. This work started not long after he came to Penn in 2002 with licensing algorithms to help drive a groundbreaking device by NeuroPace, the first closed-loop, responsive neurostimulator to treat epilepsy.

Building on this work, Litt noted in 2011 how the implantable neurostimulation devices being used at the time had rigid wires that didn’t conform to the brain’s surface, and he received support from CURE Epilepsy to accelerate the development of newer, flexible wires to monitor and stimulate the brain.

“CURE is one of the epilepsy community’s most influential funding organizations,” Litt says. “Their support for my lab has been incredibly helpful in enabling the cutting-edge research that we hope will change epilepsy care for our patients.”

Read the full story in Penn Today.

Brian Litt is a Professor in Bioengineering and Neurology.

Flavia Vitale is an Assistant Professor in Neurology with a secondary appointment in Bioengineering.

Jonathan Viventi is an Assistant Professor in Biomedical Engineering at Duke University.

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Gregory Bowman Appointed Penn Integrates Knowledge University Professor

by Ron Ozio

Greg Bowman
Gregory Bowman, the Louis Heyman University Professor, has joint appointments in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science. (Image: Courtesy of School of Engineering and Applied Sciences)

Gregory R. Bowman, a pioneer of biophysics and data science, has been named a Penn Integrates Knowledge University Professor at the University of Pennsylvania. The announcement was made today by President Liz Magill and Interim Provost Beth A. Winkelstein.

Bowman holds the Louis Heyman University Professorship, with joint appointments in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Bioengineering in the School of Engineering and Applied Science.

His research aims to combat global health threats such as COVID-19 and Alzheimer’s disease by better understanding how proteins function and malfunction, especially through new computational and experimental methods that map protein structures. This understanding of protein dynamics can lead to effective new treatments for even the most seemingly resistant diseases.

“Delivering the right treatment to the right person at the right time is vital to sustaining—and saving—lives,” Magill said. “Greg Bowman’s novel work holds enormous promise and potential to advance new forms of personalized medicine, an area of considerable strength for Penn. A gifted researcher and consummate collaborator, we are delighted to count him among our distinguished PIK University Professors.”

Bowman came to Penn from the Washington University School of Medicine’s Department of Biochemistry and Molecular Biophysics, where he served on the faculty since 2014. He previously completed a three-year postdoctoral fellowship at the University of California, Berkeley.

Bowman’s research utilizes high-performance supercomputers for simulations that can better explain how mutations and disease change a protein’s functions. These simulations are enabled in part through the innovative Folding@home project, which Bowman directs. Folding@home empowers anyone with a computer to run simulations alongside a consortium of universities, with more than 200,000 participants worldwide.

His research has been supported by the National Science Foundation, National Institutes of Health, National Institute on Aging, and Packard Foundation, among others, and he has received a CAREER Award from the NSF, Career Award at the Scientific Interface from the Burroughs Wellcome Fund, and Thomas Kuhn Paradigm Shift Award from the American Chemical Society. He received a Ph.D. in biophysics from Stanford University and a B.S. (summa cum laude) in computer science, with a minor in biomedical engineering, from Cornell University.

“Greg Bowman’s highly innovative work,” Winkelstein said, “exemplifies the power of our interdisciplinary mission at Penn. He brings together supercomputers, biophysics, and biochemistry to make a vital impact on public health. This brilliant fusion of methods—in the service of improving people’s lives around the world—will be a tremendous model for the research of our faculty, students, and postdocs in the years ahead.”

The Penn Integrates Knowledge program is a University-wide initiative to recruit exceptional faculty members whose research and teaching exemplify the integration of knowledge across disciplines and who are appointed in at least two schools at Penn.

The Louis Heyman University Professorship is a gift of Stephen J. Heyman, a 1959 graduate of the Wharton School, and his wife, Barbara Heyman, in honor of Stephen Heyman’s uncle. Stephen Heyman is a University Emeritus Trustee and member of the School of Nursing Board of Advisors. He is Managing Partner at Nadel and Gussman LLC in Tulsa, Oklahoma.

This story originally appeared in Penn Today.

Dr. Bowman is Penn Bioengineering’s third PIK Professor after Kevin Johnson and Konrad Kording. See the full list of University PIK Professors here.

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More Cancers May be Treated with Drugs than Previously Believed

by Alex Gardner

3D illustration of cancer cells
nucleus and membrane of pathogen micro organisms in blue background

Up to 50 percent of cancer-signaling proteins once believed to be immune to drug treatments due to a lack of targetable protein regions may actually be treatable, according to a new study from the Perelman School of Medicine at the University of Pennsylvania. The findings, published this month in Nature Communications, suggest there may be new opportunities to treat cancer with new or existing drugs.

Researchers, clinicians, and pharmacologists looking to identify new ways to treat medical conditions—from cancer to autoimmune diseases—often focus on protein pockets, areas within protein structures to which certain proteins or molecules can bind. While some pockets are easily identifiable within a protein structure, others are not. Those hidden pockets, referred to as cryptic pockets, can provide new opportunities for drugs to bind to. The more pockets scientists and clinicians have to target with drugs, the more opportunities they have to control disease.

The research team identified new pockets using a Penn-designed neural network, called PocketMiner, which is artificial intelligence that predicts where cryptic pockets are likely to form from a single protein structure and learns from itself. Using PocketMiner—which was trained on simulations run on the world’s largest super computer—researchers simulated single protein structures and successfully predicted the locations of cryptic pockets in 35 cancer-related protein structures in thousands of areas of the body. These once-hidden targets, now identified, open up new approaches for potentially treating existing cancer.

What’s more, while successfully predicting the cryptic pockets, the method scientists used in this study was much faster than previous simulation or machine-learning methods. The network allows researchers to nearly instantaneously decide if a protein is likely to have cryptic pockets before investing in more expensive simulations or experiments to pursue a predicted pocket further.

“More than half of human proteins are considered undruggable due to an apparent lack of binding proteins in the snapshots we have,” said Gregory R. Bowman, PhD, a professor of Biochemistry and  Biophysics and Bioengineering at Penn and the lead author of the study. “This PocketMiner research and other research like it not only predict druggable pockets in critical protein structures related to cancer but suggest most human proteins likely have druggable pockets, too. It’s a finding that offers hope to those with currently untreatable diseases.”

Read the full story in Penn Medicine News.

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2022 PIP/PEP Prize Winners: Where are they now?

by Brandon Baker

William Danon and Luka Yancopoulos pose in front of College Hall in April 2022. They are co-founders of Grapevine and the winners of the 2022 President’s Innovation Prize. (Photo: Eric Sucar)

In April 2022, three President’s Prize-winning teams were selected from an applicant pool of 71 people to develop projects that promote engagement and innovation. Each project received $100,000, as well as a $50,000 living stipend per team member.

The President’s Innovation Prize and President’s Engagement Prize winners included Grapevine, which aims to better connect buyers and suppliers to stabilize the medical supply chain market; IF Ventures, with its mission to scale impact by supporting college students with early-stage startup ideas that have measurable social and environmental impact; and Cosmic Writers, which organizes writing workshops to cultivate K-12 students to be better writers and communicators — and, therefore, better citizens.

“In less than a year, these three PIP and PEP prize-winning teams have already proven their commitment to making a difference in the world,” says President Liz Magill. “Their projects are ambitious and inspiring, and I am proud the University has been able to provide financial and networking support for these determined changemakers.”

Grapevine, 2022 President’s Innovation Prize Winners

After graduating in May 2022, Luka Yancopoulos, an Environmental Studies major and a Bioengineering major in the School of Engineering and Applied Science and William Danon, a History major, relocated to an office space in Westchester, New York, and got to work on a research and validation process — first, by spending a day at a Penn Medicine facility, Lancaster General Health, then by committing hundreds of hours to interviewing distributor and procurement teams alike, along with potential client companies. The mission, as any researcher knows, was to understand key pain points. They also onboarded veterans in logistics, technology, and payment security and processing while devising an organizational structure in which Yancopoulous leads on technology and design solutions while Danon interfaces with customers to know what needs remain unmet.

Grapevine soft launched in fall 2022 and, they say, has interfaced with 30 companies through its digital platform to facilitate sales among 40 suppliers, amounting to more than $20,000 in transactions. The appeal of the platform, they say, remains the concept of the “digital supply chain network,” which Yancopoulos says partners can use to connect with resellers, hospitals, distributors, and others to reduce the risk of supply chain disruption that is not just a product of the pandemic, he adds, but “forever ongoing.”

“It’s driven by the principle that together we’re stronger, and I mean that in every aspect of my life,” he says. “That people are stronger, and with Grapevine we work to [bolster] supply chains and increase the accessibility of health care products — together.”

Since winning the President’s Innovation Prize, they’ve focused on working with small- to medium-sized businesses — whether local clinics or high-quality, specialized resellers — that struggle to compete with or pay for traditional, large-scale distributors that are better-resourced or too expensive. It’s allowed them to also find new users, like health care-adjacent businesses including funeral homes and tattoo parlors.

Their current tagline: “Grow with us,” Danon says.

Watch a video overview of Grapevine’s progress since receiving the PIP prize and read more about the other PIP/PEP prize winners at Penn Today.

Read more stories featuring Grapevine.

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A Potential Strategy to Improve T Cell Therapy in Solid Tumors

A new Penn Medicine preclinical study demonstrates a simultaneous ‘knockout’ of two inflammatory regulators boosts T cell expansion to attack solid tumors.

by Meagan Raeke

Image: Courtesy of Penn Medicine News

A new approach that delivers a “one-two punch” to help T cells attack solid tumors is the focus of a preclinical study by researchers from the Perelman School of Medicine. The findings, published in the Proceedings of the National Academy of Sciences, show that targeting two regulators that control gene functions related to inflammation led to at least 10 times greater T cell expansion in models, resulting in increased anti-tumor immune activity and durability.

CAR T cell therapy was pioneered at Penn Medicine by Carl H. June, the Richard W. Vague Professor in Immunotherapy at Penn and director of the Center for Cellular Immunotherapies (CCI) at Abramson Cancer Center, whose work led to the first approved CAR T cell therapy for B-cell acute lymphoblastic leukemia in 2017. Since then, personalized cellular therapies have revolutionized blood cancer treatment, but remained stubbornly ineffective against solid tumors, such as lung cancer and breast cancer.

“We want to unlock CAR T cell therapy for patients with solid tumors, which include the most commonly diagnosed cancer types,” says June, the new study’s senior author. “Our study shows that immune inflammatory regulator targeting is worth additional investigation to enhance T cell potency.”

One of the challenges for CAR T cell therapy in solid tumors is a phenomenon known as T cell exhaustion, where the persistent antigen exposure from the solid mass of tumor cells wears out the T cells to the point that they aren’t able to mount an anti-tumor response. Engineering already exhausted T cells from patients for CAR T cell therapy results in a less effective product because the T cells don’t multiply enough or remember their task as well.

Previous observational studies hinted at the inflammatory regulator Regnase-1 as a potential target to indirectly overcome the effects of T cell exhaustion because it can cause hyperinflammation when disrupted in T cells—reviving them to produce an anti-tumor response. The research team, including lead author David Mai, a bioengineering graduate student in the School of Engineering and Applied Science, and co-corresponding author Neil Sheppard, head of the CCI T Cell Engineering Lab, hypothesized that targeting the related, but independent Roquin-1 regulator at the same time could boost responses further.

“Each of these two regulatory genes has been implicated in restricting T cell inflammatory responses, but we found that disrupting them together produced much greater anti-cancer effects than disrupting them individually,” Mai says. “By building on previous research, we are starting to get closer to strategies that seem to be promising in the solid tumor context.”

Read the full story in Penn Medicine News.

June is a member of the Penn Bioengineering Graduate Group. Read more stories featuring June’s research here.

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Carl June and Avery Posey Lead the Way in CAR T Cell Therapy

Perelman School of Medicine (PSOM) professors and Penn Bioengineering Graduate Group members Carl June and Avery Posey are leading the charge in T cell therapy and the fight against cancer.

Avery Posey, PhD
Carl June, MD

Advances in genome editing through processes such as CRISPR, and the ability to rewire cells through synthetic biology, have led to increasingly elaborate approaches for modifying and supercharging T cells for therapy. Avery Posey,  Assistant Professor of Pharmacology, and Carl June, the Richard W. Vague Professor in Immunotherapy, explain how new techniques are providing tools to counter some of the limitations of current CAR T cell therapies in a recent Nature feature.

The pair were also part of a team of researchers from PSOM, the Children’s Hospital of Philadelphia (CHOP), and the Corporal Michael J. Crescenz VA Medical Center to receive an inaugural $8 million Therapy ACceleration To Intercept CAncer Lethality (TACTICAL) Award from the Prostate Cancer Foundation. Their project will develop new clinic-ready CAR T cell therapies for Metastatic Castrate-Resistant Prostate Cancer (mCRPC).

Read “The race to supercharge cancer-fighting T cells” in Nature.

Read about the TACTICAL Award in the December 2022 Awards & Accolades section of Penn Medicine News.

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RNA Lipid Nanoparticle Engineering Stops Liver Fibrosis in its Tracks, Reverses Damage

by Melissa Pappas

Members of the research team include (from left to right) Xuexiang Han, Michael J. Mitchell, Ningqiang Gong, Lulu Xue, Sarah J. Shepherd, and Rakan El-Mayta.
Members of the research team include (from left to right) Xuexiang Han, Michael J. Mitchell, Ningqiang Gong, Lulu Xue, Sarah J. Shepherd, and Rakan El-Mayta.

Since the success of the COVID-19 vaccine, RNA therapies have been the object of increasing interest in the biotech world. These therapies work with your body to target the genetic root of diseases and infections, a promising alternative treatment method to that of traditional pharmaceutical drugs.

Lipid nanoparticles (LNPs) have been successfully used in drug delivery for decades. FDA-approved therapies use them as vehicles for delivering messenger RNA (mRNA), which prompts the cell to make new proteins, and small interfering RNA (siRNA), which instruct the cell to silence or inhibit the expression of certain proteins.

The biggest challenge in developing a successful RNA therapy is its targeted delivery. Research is now confronting the current limitations of LNPs, which have left many diseases without an effective RNA therapy.

Liver fibrosis occurs when the liver is repeatedly damaged and the healing process results in the accumulation of scar tissue, impeding healthy liver function. It is a chronic disease characterized by the buildup of excessive collagen-rich extracellular matrix (ECM). Liver fibrosis has remained challenging to treat using RNA therapies due to a lack of delivery systems for targeting activated liver-resident fibroblasts. Both the solid fibroblast structure and the lack of specificity or affinity to target these fibroblasts has impeded current LNPs from entering activated liver-resident fibroblasts, and thus they are unable to deliver RNA therapeutics.

To tackle this issue and help provide a treatment for the millions of people who suffer from this chronic disease, Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, and postdoctoral fellows Xuexiang Han and Ningqiang Gong, found a new way to synthesize ligand-tethered LNPs, increasing their selectivity and allowing them to target liver fibroblasts.

Lulu Xue, Margaret Billingsley, Rakan El-Mayta, Sarah J. Shepherd, Mohamad-Gabriel Alameh and Drew Weissman, Roberts Family Professor in Vaccine Research and Director of the Penn Institute for RNA Innovation at the Perelman School of Medicine, also contributed to this work.

Read the full story in Penn Engineering Today.