news – Page 6 – Penn Bioengineering Blog

March 24, 2023March 23, 2023

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.

March 22, 2023

Building Devices and a “Sense of Community”: Penn Bioengineering Labs Featured in Technical.ly Philly

Penn Bioengineering juniors work on their ECG devices in BE 3100, Bioengineering Modeling, Analysis and Design Laboratory II (aka BE MAD)

The George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace (aka the Penn BE Labs) played host last week to Sarah Huffman, a local journalist writing for Technical.ly Philly. During her visit to the lab, she chatted with third year undergraduates working on their ECG devices for monitoring breathing and heart rates, and senior design students applying all they’ve learned in their previous three years to their graduation capstone projects. She also got a chance to discuss the classes and learn about the lab’s vision to be a bio-makerspace with Sevile Mannickarottu, Director of Educational Labs for BE, and with David Issadore, Associate Professor in Bioengineering and in Electrical and Systems Engineering and professor of the third year spring lab course:

Journalist Sarah Huffman interviews BE 3100 professor David Issadore.

“’The students all come here and they hang out and they build stuff,’ said David Issadore, associate professor of bioengineering and electrical and systems engineering. ‘This junior-level course is kind of an entry point for their senior design. So next year, all these students are going to take on new projects, and then they all kind of hang around here and they build incredible stuff.’”

The profile of the BE Labs is part of Technical.ly’s 2023 Universities Month, a series focusing on the latest trends and tech in higher education.

Read “Peek into an afternoon at Penn’s collaborative bioengineering lab and makerspace” in Technical.ly.

Read more stories featuring the Penn BE Labs.

March 17, 2023

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

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.

March 8, 2023

Student Summer Research Spotlight: Dahin Song

Dahin Song, a third year undergraduate student in Bioengineering, penned a guest blog post for Penn Career Services as part of their ongoing series of posts by recipients of the 2022 Career Services Summer Funding Grant. In this post, Song talks about her opportunity to conduct research in the SMART Lab of Daeyeon Lee, Professor and Evan C. Thompson Term Chair for Excellence in Teaching in the Department of Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group. During her summer research, Song worked on increasing the stability of the monolayer in microbubbles, gas particles which have been put to therapeutic use. She writes:

“My project was on increasing the stability of the monolayer using cholesterol; theoretically, this would decrease the permeability while maintaining the fluidity of the monolayer. Being given my own project at the get-go was initially intimidating; initial learning curve was overwhelming – along with new wet lab techniques and protocols, I learned a whole new topic well enough to ask meaningful questions. But in retrospect, throwing myself headlong into a project was the best method to immerse me in the research environment, especially as a first-time researcher. I learned how to read papers efficiently, troubleshoot research problems, navigate in a laboratory environment, and be comfortable with working independently but more importantly, with others.”

Read “The Itsy Bitsy Bubble” in the Career Services blog.

February 13, 2023February 15, 2023

Penn Bioengineering Student is a Hertz Fellowship Finalist

Savan Patel, a fourth year Penn Bioengineering student, is one of 42 finalists competing for a 2023 Hertz Fellowship in applied science, mathematics, and engineering, one of the most prestigious Ph.D. fellowships in the United States. Chosen annually, the Hertz Fellowship is awarded to the nation’s most promising graduate students in science and technology.

From the Hertz Foundation website:

“Since 1963, the Hertz Foundation has granted fellowships empowering the nation’s most promising young minds in science and technology. Hertz Fellows receive five years of funding valued at up to $250,000, which offers flexibility from the traditional constraints of graduate training and the independence needed to pursue research that best advances our security and economic vitality […]

Over the foundation’s 60-year history of awarding fellowships, more than 1200 Hertz Fellows have established a remarkable track record of accomplishments. Their ranks include two Nobel laureates; recipients of 10 Breakthrough Prizes and three MacArthur Foundation “genius awards”; and winners of the Turing Award, the Fields Medal, the National Medal of Technology, and the National Medal of Science. In addition, 50 are members of the National Academies of Sciences, Engineering and Medicine, and 34 are fellows of the American Association for the Advancement of Science. Hertz Fellows hold over 3,000 patents, have founded more than 375 companies and have created hundreds of thousands of science and technology jobs.”

Patel is studying Bioengineering and Finance in the Jerome Fisher Program in Management and Technology (M&T), an interdisciplinary dual degree program coordinated by Penn Engineering and the Wharton School of Business. He is currently a member of the lab of Michael J. Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering. Patel’s research interests lie at the interface of drug delivery and immunoengineering. His current project involves the use of modified cholesterol molecules to induce shifts in the biodistribution of ionizable lipid nanoparticles (LNPs). Following graduation, he intends to pursue a Ph.D. in bioengineering in which hopes to develop translatable immunotherapies and drug delivery platforms.

If chosen, the Hertz Fellowship will fund Patel’s graduate studies. Selected from over 750 applicants, Patel is one of fifteen undergraduates and one of two bioengineering students to make the final round of interviews. After a culminating round of interviews, the 2023 Class of Hertz Fellows will be announced in May.

Learn more about the Hertz Fellowship and read the full list of finalists here.

February 7, 2023February 7, 2023

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.

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.

February 6, 2023February 6, 2023

“Creativity needs to let go of control”: Penn BE Labs Featured on the Shifting Schools Podcast

Shifting Schools. Sevile Mannickarottu, @PennBELabs. Thanks to our sponsors: STEM Sports & MackinMaker. — Sevile Mannickarottu, Director of Educational Labs, Penn Bioengineering

Sevile Mannickarottu, Director of Educational Laboratories in the Department of Bioengineering (BE), was interviewed in a recent episode of Shifting Schools, a weekly podcast that hosts educators and thought-leaders in conversations about the latest trends in education and EdTech. Mannickarottu, a Penn Engineering alumnus, runs the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, also known as the Penn BE Labs. In addition to being the primary teaching lab for Penn Bioengineering, the Penn BE Labs has grown into “the world’s only interdisciplinary Bio-MakerSpace.”

Students busy at work in the Penn BE Labs.

MakerSpaces–collaborative, educational work environments–have recently grown in popularity. Penn BE Labs distinguishes itself as a Bio-MakerSpace, embracing the interdisciplinary character of bioengineering by offering itself freely as a space for both academic and personal projects. It is stocked with tools ranging from 3D printers, laser cutters, and electrical equipment, including supplies to support work in molecular biology, physiology, chemistry, and microfluidics.

In the episode, hosts Tricia Friedman and Jeff Utecht talk with Mannickarottu about the organic process by which the Penn BE Labs evolved from a standard teaching space for undergraduate engineering laboratory courses into a student-driven hub of creativity and entrepreneurial spirit that is open to the entire Penn community regardless of discipline or major.

A student using the BE Labs' sewing machine for a project. Mannickarottu and his team have found that “creativity needs to let go of control – that’s when fun things happen.” As the lab staff and faculty started to allow more creative freedom in the undergraduate bioengineers’ education, the requests for more supplies started pouring in and the lab’s activities and resources grew. “Honestly, we’re driven almost entirely by student requests and student demands,” says Mannickarottu. So when a student requested a sewing machine for a project? They went out and bought one, adding to their ever-growing stockpile of tools. Over time, more and more diverse projects have emerged from the BE Labs, many of them going on to win awards and grow beyond Penn’s campus as independent startups.

In case this sounds out of reach for smaller institutions, Mannickarottu shares words of encouragement. “The biggest thing,” he says, “is to allow for creativity on the part of the students.” A lab or program can start their own MakerSpace surprisingly inexpensively and build their inventory over time. His number one recommendation for those looking to replicate the success of Penn BE Labs is to allow students freedom to innovate, and administrators will be drawn to invest in the MakerSpace to allow for even more opportunities for them to create and thrive.

BE Labs logo To help others get started, the Penn BE Labs staff have put a wide range of resources online, including extensive video and photo archives, FAQ’s, tutorials, information about student projects and startups, and equipment inventories. A 2019 post written for the BE Blog by BE alumna Sophie Burkholder (BSE ‘20 & MSE ‘21) gives the reader tips on “how to build your own MakerSpace for under $1500.”

Though it may currently be “the world’s only interdisciplinary Bio-MakerSpace,” the greatest legacy of the Penn BE Labs would be to be known as the first of many.

Listen to “The legacy of your lab” in Shifting Schools to learn more about the Penn BE Labs and for tips on starting your own MakerSpace.

January 19, 2023

ASSET Center Inaugural Seed Grants Will Fund Trustworthy AI Research in Healthcare

by Devorah Fischler

Penn Engineering’s newly established ASSET Center aims to make AI-enabled systems more “safe, explainable and trustworthy” by studying the fundamentals of the artificial neural networks that organize and interpret data to solve problems.

ASSET’s first funding collaboration is with Penn’s Perelman School of Medicine (PSOM) and the Penn Institute for Biomedical Informatics (IBI). Together, they have launched a series of seed grants that will fund research at the intersection of AI and healthcare.

Teams featuring faculty members from Penn Engineering, Penn Medicine and the Wharton School applied for these grants, to be funded annually at $100,000. A committee consisting of faculty from both Penn Engineering and PSOM evaluated 18 applications and judged the proposals based on clinical relevance, AI foundations and potential for impact.

Artificial intelligence and machine learning promise to revolutionize nearly every field, sifting through massive amounts of data to find insights that humans would miss, making faster and more accurate decisions and predictions as a result.

Applying those insights to healthcare could yield life-saving benefits. For example, AI-enabled systems could analyze medical imaging for hard-to-spot tumors, collate multiple streams of disparate patient information for faster diagnoses or more accurately predict the course of disease.

Given the stakes, however, understanding exactly how these technologies arrive at their conclusions is critical. Doctors, nurses and other healthcare providers won’t use such technologies if they don’t trust that their internal logic is sound.

“We are developing techniques that will allow AI-based decision systems to provide both quantifiable guarantees and explanations of their predictions,” says Rajeev Alur, Zisman Family Professor in Computer and Information Science and Director of the ASSET Center. “Transparency and accuracy are key.”

“Development of explainable and trustworthy AI is critical for adoption in the practice of medicine,” adds Marylyn Ritchie, Professor of Genetics and Director of the Penn Institute for Biomedical Informatics. “We are thrilled about this partnership between ASSET and IBI to fund these innovative and exciting projects.”

Seven projects were selected in the inaugural class, including projects from Dani S. Bassett, J. Peter Skirkanich Professor in the Departments of Bioengineering, Electrical and Systems Engineering, Physics & Astronomy, Neurology, and Psychiatry, and several members of the Penn Bioengineering Graduate Group: Despina Kontos, Matthew J. Wilson Professor of Research Radiology II, Department of Radiology, Penn Medicine and Lyle Ungar, Professor, Department of Computer and Information Science, Penn Engineering; Spyridon Bakas, Assistant Professor, Departments of Pathology and Laboratory Medicine and Radiology, Penn Medicine; and Walter R. Witschey, Associate Professor, Department of Radiology, Penn Medicine.

Optimizing clinical monitoring for delivery room resuscitation using novel interpretable AI

Elizabeth Foglia, Associate Professor, Department of Pediatrics, Penn Medicine and the Children’s Hospital of Philadelphia

Dani S. Bassett, J. Peter Skirkanich Professor, Departments of Bioengineering and Electrical and Systems Engineering, Penn Engineering

This project will apply a novel interpretable machine learning approach, known as the Distributed Information Bottleneck, to solve pressing problems in identifying and displaying critical information during time-sensitive clinical encounters. This project will develop a framework for the optimal integration of information from multiple physiologic measures that are continuously monitored during delivery room resuscitation. The team’s immediate goal is to detect and display key target respiratory parameters during delivery room resuscitation to prevent acute and chronic lung injury for preterm infants. Because this approach is generalizable to any setting in which complex relations between information-rich variables are predictive of health outcomes, the project will lay the groundwork for future applications to other clinical scenarios.

Read the full list of projects and abstracts in Penn Engineering Today.

January 13, 2023

Alex Hughes Named CMBE Rising Star

A collage of photos: Alex Hughes presenting, the title slide of his presentation with the title "Interpreting geometric rules of early kidney formation for synthetic morphogenesis," and his acknowledgements slides. — Alex J. Hughes presents at the BMES CMBE conference in January 2023. (Image credit: Riccardo Gottardi, Assistant Professor in Pediatrics and Bioengineering)

Alex J. Hughes, Assistant Professor in the Department of Bioengineering, was one of thirteen recipients of the 2023 Rising Star Award for Junior Faculty by the Cellular and Molecular Bioengineering (CMBE) Special Interest Group. The Rising Star Award recognizes a CMBE member in their early independent career stage that has made an outstanding impact on the field of cellular and molecular bioengineering. CMBE is a special interest group of the Biomedical Engineering Society (BMES), the premier professional organization of bioengineers.

The Hughes Lab in Penn Bioengineering works to “bring developmental processes that operate in vertebrate embryos and regenerating organs under an engineering control framework” in order to “build better tissues.” Hughes’s research interest is in harnessing the developmental principles of organs, allowing him to design medically relevant scaffolds and machines. In 2020 he became the first Penn Engineering faculty member to receive the Maximizing Investigators’ Research Award (MIRA) from the National Institutes of Health (NIH), and he was awarded a prestigious CAREER Award from the National Science Foundation (NSF) in 2021. Most recently, Hughes’s work has focused on understanding the development of cells and tissues in the human kidney via the creation of “organoids”: miniscule organ models that can mimic the biochemical and mechanical properties of the developing kidney. Understanding and engineering how the kidney functions could open doors to more successful regenerative medicine strategies to address highly prevalent congenital and adult diseases.

Hughes and his fellow award recipients were recognized at the annual BMES CBME conference in Indian Wells, CA in January 2023.

Read the full list of 2023 CMBE Award Winners.

January 6, 2023

CAR T Cell Therapy Reaches Beyond Cancer

Penn Medicine researchers laud the early results for CAR T therapy in lupus patients, which point to broader horizons for the use of personalized cellular therapies.

Penn Medicine’s Carl June and Daniel Baker.

Engineered immune cells, known as CAR T cells, have shown the world what personalized immunotherapies can do to fight blood cancers. Now, investigators have reported highly promising early results for CAR T therapy in a small set of patients with the autoimmune disease lupus. Penn Medicine CAR T pioneer Carl June and Daniel Baker, a doctoral student in cell and molecular biology in the Perelman School of Medicine, discuss this development in a commentary published in Cell.

“We’ve always known that in principle, CAR T therapies could have broad applications, and it’s very encouraging to see early evidence that this promise is now being realized,” says June, who is the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine at Penn Medicine and director of the Center for Cellular Immunotherapies at the Abramson Cancer Center.

T cells are among the immune system’s most powerful weapons. They can bind to, and kill, other cells they recognize as valid targets, including virus-infected cells. CAR T cells are T cells that have been redirected, through genetic engineering, to efficiently kill specifically defined cell types.

CAR T therapies are created out of each patient’s own cells—collected from the patient’s blood, and then engineered and multiplied in the lab before being reinfused into the patient as a “living drug.” The first CAR T therapy, Kymriah, was developed by June and his team at Penn Medicine, and received Food & Drug Administration approval in 2017. There are now six FDA-approved CAR T cell therapies in the United States, for six different cancers.

From the start of CAR T research, experts believed that T cells could be engineered to fight many conditions other than B cell cancers. Dozens of research teams around the world, including teams at Penn Medicine and biotech spinoffs who are working to develop effective treatments from Penn-developed personalized cellular therapy constructs, are examining these potential new applications. Researchers say lupus is an obvious choice for CAR T therapy because it too is driven by B cells, and thus experimental CAR T therapies against it can employ existing anti-B-cell designs. B cells are the immune system’s antibody-producing cells, and, in lupus, B cells arise that attack the patient’s own organs and tissues.

This story is by Meagan Raeke. Read more at Penn Medicine News.

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