Tag: Perelman

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Leveraging the Body’s Postal System to Understand and Treat Disease

by Nathi Magubane

Microwell device with a solution in the reservoir (Image: Courtesy of David E. Reynolds)

Akin to the packages sent from one person to another via an elaborate postal system, cells send tiny parcels that bear contents and packaging material that serve key purposes: To protect the contents from the outside world and to make sure it gets to the right place via a label with an address. 

These packages are known as extracellular vesicles (EVs)—lipid-bound molecules that serve a variety of regulatory and maintenance functions throughout the body. They assist in the removal of unwanted materials within the cell, and they transport proteins, aid in DNA and RNA transfer, and promote tumorigeneses in cancerous cells. 

Given their myriad roles, EVs have taken center stage for many researchers in the biomedical space as they have the potential to improve current methods of disease detection and treatment. The main challenge, however, is accurately identifying the molecular contents of EVs while also characterizing the EVs, which, unlike other cellular components that are more homogenous, have more heterogeneity.

Now, a team of researchers at the University of Pennsylvania has developed a novel platform, droplet-free double digital assay, for not only profiling individual EVs but also accurately discerning their molecular contents. The researchers took the digital assay, which quantifies the contents of a molecule via binary metric—a 1 corresponds to the presence of a molecule and a zero to the lack thereof—and applies it to the EV. The work is published in Advanced Science.

The team was led by Jina Ko, an assistant professor with appointments in the School of Engineering and Applied Science and Perelman School of Medicine. “Our method allows for highly accurate quantification of the individual molecules inside an EV,” Ko says . “This opens up many doors in the realm of early disease detection and treatment.”

The researchers first compartmentalized individual EVs utilizing a microwell approach to isolate the EVs. Next, they captured individual molecules within the EVs and amplified the signal for clarity. The team then was able to determine the expression levels of pivotal EV biomarkers with remarkable precision via fluorescence.

Read the full story in Penn Today.

Jina Ko is an assistant professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine and an assistant professor in the Department of Bioengineering in the School of Engineering and Applied Science at the University of Pennsylvania.

David Reynolds is a Ph.D. candidate in the Department of Bioengineering in Penn Engineering.

Other authors include, Menghan Pan, George Galanis, Yoon Ho Roh, Renee-Tyler T. Morales, Shailesh Senthil Kumar, and Su-Jin Heo of the Department of Bioengineering at Penn Engineering; Jingbo Yang and Xiaowei Xu of the Department of Pathology and Laboratory Medicine at Penn Medicine; and Wei Guo of the Department of Biology in the School of Arts & Sciences at Penn.

The research was supported by the National Institutes of Health: grants R00CA256353, R35 GM141832, and CA174523 (SPORE).

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The Immune Health Future, Today

by Christina Hernandez Sherwood

Breaking the code of the immune system could provide a new fundamental way of understanding, treating, and preventing every type of disease. Penn Medicine is investing in key discoveries about immunity and immune system function, and building infrastructure, to make that bold idea a reality.

Several members of the Penn Bioengineering Graduate Group feature in this story which originally featured in the Penn Medicine Magazine.

Image: Courtesy of Penn Medicine Magazine

This grandfather lives with primary progressive multiple sclerosis (MS), an autoimmune disorder that he controls with a medicine that depletes his body of the type of immune cells that make antibodies. So while he has completed his COVID-19 vaccine course, his immune system function isn’t very strong—and the invitation has arrived at a time when COVID-19 is still spreading rapidly. 

You can imagine the scene as an older gentleman lifts a thick, creamy envelope from his mailbox, seeing his own name written in richly scripted lettering. He beams with pride and gratitude at the sight of his granddaughter’s wedding invitation. Yet his next thought is a sober and serious one. Would he be taking his life in his hands by attending the ceremony?

“In the past, all we could do was [measure] the antibody response,” says Amit Bar-Or, the Melissa and Paul Anderson President’s Distinguished Professor in Neurology at the Perelman School of Medicine, and chief of the Multiple Sclerosis division. “If that person didn’t have a good antibody response, which is likely because of the treatment they’re on, we’d shrug our shoulders and say, ‘Maybe you shouldn’t go because we don’t know if you’re protected.’” 

Today, though, Bar-Or can take a deeper dive into his patients’ individual immune systems to give them far more nuanced recommendations. A clinical test for immune cells produced in response to the COVID-19 vaccine or to the SARS-CoV-2 virus itself—not just antibodies—was one of the first applied clinical initiatives of a major new Immune Health® project at Penn Medicine. Doctors were able to order this test and receive actionable answers through the Penn Medicine electronic health record for patients like the grandfather with MS. 

“With a simple test and an algorithm we can have a very different discussion,” Bar-Or says. A test result showing low T cells, for instance, would tell Bar-Or his patient may get a meaningful jolt in immunity from a vaccine booster, while low antibody levels would suggest passive antibody therapy is more helpful. Or, the test might show his body is already well primed to protect him, making it reasonably safe to attend the wedding.

This COVID-19 immunity test is only the beginning. 

Physicians and scientists at Penn Medicine are imagining a future where patients can get a precise picture of their immune systems’ activity to guide treatment decisions. They are working to bring the idea of Immune Health to life as a new area of medicine. In labs, in complex data models, and in the clinic, they are beginning to make sense out of the depth and breadth of the immune system’s millions of as-yet-undeciphered signals to improve health and treat illnesses of all types. 

Penn Medicine registered the trademark for the term “Immune Health” in recognition of the potential impact of this research area and its likelihood to draw non-academic partners as collaborators in its growth. Today, at the south end of Penn’s medical campus, seven stories of research space are being added atop an office building at 3600 Civic Center Blvd., including three floors dedicated to Immune Health, autoimmunity, and immunology research.

The concept behind the whole project, says E. John Wherry, director of Penn Medicine’s Institute for Immunology and Immune Health (I3H), “is to listen to the immune system, to profile the immune system, and use those individual patient immune fingerprints to diagnose and treat diseases as diverse as immune-related diseases, cancer, cardiovascular disease, Alzheimer’s, and many others.”

The challenge is vast. Each person’s immune system is far more complex than antibodies and T cells alone. The immune system is made of multiple interwoven layers of complex defenders—from our skin and mucous membranes to microscopic memory B cells that never forget a childhood infection—meant to fortify our bodies from germs and disease. It is a sophisticated system that learns and adapts over our lifetimes in numerous ways, and it also falters and fails in some ways we understand and others that remain mysterious. And each person’s intricate internal battlefield is in some way unique.

The immune system is not just a set of defensive barricades, either. It’s also a potential source of deep insight about a person’s physiological functioning and responses to medical treatments.

“The immune system is sensing and keeping track of basically all tissues and all cells in our body all the time,” Wherry says. “It is surveying the body trying to clean up any invaders and restore homeostasis by maintaining good health.”

“Our goal is to essentially break the code of the immune system,” says Jonathan Epstein, executive vice dean of the Perelman School of Medicine and chief scientific officer at Penn Medicine. “By doing so, we believe we will be able to determine your state of health and your response to therapies in essentially every human disease.”

Read the full story in Penn Today.

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Two Penn Bioengineers Receive NIH Director Award

by Nathi Magubane

Jina Ko (left) and Kevin Johnson (right), both from the School of Engineering and the Perelman School of Medicine with appointments in Bioengineering, have received the National Institute of Health Director’s Award to support their “highly innovative and broadly impactful” research projects through the High-Risk, High-Reward program.

The National Institutes of Health (NIH) has awarded grants to three researchers from the University of Pennsylvania through the NIH Common Fund’s High-Risk, High-Reward Research program. The research of Kevin B. Johnson, Jina Ko, and Sheila Shanmugan will be supported through the program, which funds “highly innovative and broadly impactful” biomedical or behavioral research by exceptionally creative scientists.

The High-Risk, High-Reward Research program catalyzes scientific discovery by supporting highly innovative research proposals that, due to their inherent risk, may struggle in the traditional peer-review process despite their transformative potential. Program applicants are encouraged to think “outside the box” and pursue trail-blazing ideas in any area of research relevant to the NIH’s mission to advance knowledge and enhance health.

Two Penn Bioengineering faculty, Johnson and Ko, are among 85 recipients for 2023.

Johnson, the David L. Cohen University Professor of Pediatrics, is a Penn Integrates Knowledge University Professor who holds appointments in the Department of Computer and Information Science in the School of Engineering and Applied Science and the Department of Biostatistics, Epidemiology, and Informatics in the Perelman School of Medicine. He also holds secondary appointments in Bioengineering, Pediatrics, and in the Annenberg School for Communication. He is widely known for his work with e-prescribing and computer-based documentation and, more recently, work communicating science to lay audiences, which includes a documentary about health-information exchange. Johnson has authored more than 150 publications and was elected to the American College of Medical Informatics, Academic Pediatric Society, National Academy of Medicine, International Association of Health Science Informatics, and American Institute for Medical and Biological Engineering.

Ko is an assistant professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine and Department of Bioengineering in the School of Engineering and Applied Science. She focuses on developing single molecule detection from single extracellular vesicles and multiplexed molecular profiling to better diagnose diseases and monitor treatment efficacy. Ko earned her Ph.D. in bioengineering at Penn in 2018, during which time she developed machine learning-based microchip diagnostics that can detect blood-based biomarkers to diagnose pancreatic cancer and traumatic brain injury. For her postdoctoral training, she worked at the Massachusetts General Hospital and the Wyss Institute at Harvard University as a Schmidt Science Fellow and a NIH K99/R00 award recipient. Ko developed new methods to profile single cells and single extracellular vesicles with high throughput and multiplexing.

Read the full announcement in Penn Today.

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Harnessing Artificial Intelligence for Real Biological Advances—Meet César de la Fuente

by Eric Horvath

In an era peppered by breathless discussions about artificial intelligence—pro and con—it makes sense to feel uncertain, or at least want to slow down and get a better grasp of where this is all headed. Trusting machines to do things typically reserved for humans is a little fantastical, historically reserved for science fiction rather than science. 

Not so much for César de la Fuente, PhD, the Presidential Assistant Professor in Psychiatry, Microbiology, Chemical and Biomolecular Engineering, and Bioengineering in Penn’s Perelman School of Medicine and School of Engineering and Applied Science. Driven by his transdisciplinary background, de la Fuente leads the Machine Biology Group at Penn: aimed at harnessing machines to drive biological and medical advances. 

A newly minted National Academy of Medicine Emerging Leaders in Health and Medicine (ELHM) Scholar, among earning a host of other awards and honors (over 60), de la Fuente can sound almost diplomatic when describing the intersection of humanity, machines and medicine where he has made his way—ensuring multiple functions work together in harmony. 

“Biology is complexity, right? You need chemistry, you need mathematics, physics and computer science, and principles and concepts from all these different areas, to try to begin to understand the complexity of biology,” he said. “That’s how I became a scientist.”

Read the full story in Penn Medicine News.

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The Future of Medicine Rises in University City: University of Pennsylvania Opens New Multi-Disciplinary Research Labs in One uCity Square

by Holly Wojcik

One uCity Square

On September 14, Wexford Science & Technology, LLC and the University of Pennsylvania announced that the University has signed a lease for new laboratory space that will usher in a wave of novel vaccine, therapeutics, and engineered diagnostics research to West Philadelphia. Research teams from Penn are poised to move into 115,000 square feet of space at One uCity Square, the 13-story, 400,000 square foot purpose-built lab and office building within the vibrant uCity Square Knowledge Community being developed by Wexford. This is the largest lease in the building, encompassing four floors, and bringing the building to over 90% leased. The building currently includes industry tenants Century Therapeutics (NASDAQ: IPSC), Integral Molecular, Exponent (NASDAQ: EXPO), and Charles River Laboratories (NYSE: CRL).

The new University space will house Penn Medicine’s Institute for RNA Innovation and Penn Engineering’s Center for Precision Engineering for Health, underscoring the University’s commitment to a multi-disciplinary and collaborative approach to research that will attract and retain the best talent and engage partners from across the region. Penn’s decision to locate at One uCity Square reinforces uCity Square’s evolution as a central cluster of academic, clinical, commercial, entrepreneurial, and amenity spaces for the area’s innovation ecosystem, and further cements Philadelphia’s position as a top life sciences market.

Jonathan Epstein, MD, Executive Vice Dean and Chief Scientific Officer of Penn Medicine, shared his anticipation for the opportunities that lie ahead: “Penn Medicine is proud to build on its existing clinical presence in uCity Square and establish an innovative and collaborative research presence at the heart of uCity Square’s multidisciplinary innovation ecosystem. This strategic move underscores our commitment to accelerating advancements in biomedical research, industry collaboration, and equipping our talented teams with the resources they need to shape the future of healthcare.”

Locating the Penn Institute for RNA Innovation in the heart of the uCity Square community brings together researchers across disciplines who are already pursuing new vaccines and treatments, and better ways to deliver them. Their shared work will help to power the next phase of vaccine discovery and development.

Likewise, anchoring the work of Penn Engineering’s Center in the One uCity Square space will allow the School’s multi-disciplinary researchers and their collaborators to advance new clinical and diagnostic methods that will focus on intelligent therapeutics, genome design, diagnostics for discovery of human biology, and engineering the human immune shield.

“Penn Engineering has made a substantial commitment to precision engineering for health, an area that is not only important and relevant to engineering, but also critical to the future of humanity,” said Vijay Kumar, Nemirovsky Family Dean of Penn Engineering. “The space in One uCity Square will add another 30,000 square feet of space for our engineers to develop technologies that will fight future pandemics, cure incurable diseases, and extend healthy life spans around the world.”

Spearheading the Penn Institute for RNA Innovation will be Drew Weissman, MD, PhD, the Roberts Family Professor for Vaccine Research, who along with Katalin Karikó, PhD, adjunct professor of Neurosurgery, discovered foundational mRNA technology that enabled the creation of vital vaccine technology, including the FDA-approved mRNA-based COVID-19 vaccines developed by Pfizer-BioNTech and Moderna.

In this new space at One uCity Square, Weissman and his research team and collaborators will further pursue their groundbreaking research efforts with a goal to develop new therapeutics and vaccines and initiate clinical trials for other devastating diseases.

In addition, two established researchers will join the Institute at One uCity Square: Harvey Friedman, MD, a professor of Infectious Diseases, who leads a team researching various vaccines. He will be joined by Vladimir Muzykantov, MD, PhD, Founders Professor in Nanoparticle Research, who focuses on several projects related to targeting the delivery of drugs, including mRNA, to create more effective, targeted pathways to deliver drugs to the vascular system, treating a wide range of diseases that impact the brain, lung, heart, and blood.

Dan Hammer, Alfred G. and Meta A. Ennis Professor in the Departments of Bioengineering and Chemical and Biomolecular Engineering in Penn Engineering and Director of the Center for Precision Engineering for Health, will oversee the Center’s innovations in diagnostics and delivery, cellular and tissue engineering, and the development of new devices that integrate novel materials with human tissues. The Center will bring together scholars from all departments within Penn Engineering and will help to foster increased collaboration with campus colleagues at Penn’s Perelman School of Medicine and with industry partners.

Joining the Center researchers in One uCity Square are Noor Momin, Sherry Gao, and Michael Mitchell. Noor Momin, who will join Penn Engineering in early 2024 as an assistant professor in Bioengineering, will leverage her lab’s expertise in cardiovascular immunology, protein engineering and pharmacokinetic modeling to develop next-generation treatments and diagnostics for cardiovascular diseases.

Read the full story in Penn Engineering Today.

Jonathan Epstein and Vladimir Muzykantov are members of the Penn Bioengineering Graduate Group.

Michael Mitchell is an Associate Professor in Bioengineering.

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Carl June to Receive 2024 Breakthrough Prize in Life Sciences

by Meagan Raeke

Image: Courtesy of Penn Medicine

CAR T cell therapy pioneer Carl June, the Richard W. Vague Professor in Immunotherapy in the Perelman School of Medicine and director of the Center for Cellular Immunotherapies (CCI) at Penn Medicine’s Abramson Cancer Center, has been named a winner of the 2024 Breakthrough Prize in Life Sciences for the development of chimeric antigen receptor (CAR) T cell immunotherapy, a revolutionary cancer treatment approach in which each patient’s T cells are modified to target and kill their cancer cells. The invention sparked a new path in cancer care, harnessing the power of patients’ own immune systems, a once-elusive goal that brought fresh options for those who could not be successfully treated with conventional approaches.

Founded in 2012, the Breakthrough Prizes are the world’s largest science awards, with $3 million awarded for each of the five main prize categories. June is the sixth Breakthrough Prize laureate from Penn, which joins Harvard and MIT among the institutions whose researchers have been honored with the most Breakthrough Prizes.

“This award is not only a testament to Dr. June’s outstanding contributions to science, but also a shining example of the caliber of discoveries and research which Penn faculty set their sights upon,” said Penn President Liz Magill. “We are immensely proud to have Dr. June as a member of the Penn academic community, and we know that CAR T cell therapy is just the first chapter in an inspiring and lifesaving new era of medicine.”

June is internationally recognized for his role in pioneering the CAR T cell therapy, which led to the first FDA-approved personalized cellular therapy, for children and young adults with the blood cancer known as acute lymphoblastic leukemia, in August of 2017—a step which has spurred five additional approvals of the technique in other blood cancers. June joined Penn in 1999, building momentum for Penn to become a global hub for cell and gene therapy. Gene-modified T cells engineered in June’s lab to retrain a patient’s own immune cells to attack cancer were used in the first clinical trial of CAR T cell therapy in 2010. Some of the earliest children and adults treated have experienced long-lasting remissions of 10 years or more. In addition to the FDA approvals that have made the therapy commercially available to patients across the world, thousands more have benefited from clinical trials testing these transformative treatments, including for the treatment of solid tumors and even autoimmune diseases like lupus.

“Dr. June’s tireless commitment to advancing T cell immunotherapy research has been life-changing for many patients affected by cancer, who have lived longer, fuller lives, thanks to the discoveries made in his lab,” said J. Larry Jameson,executive vice president of the University of Pennsylvania for the Health System and dean of the Perelman School of Medicine. “We are proud to see one of Penn’s most esteemed scientists recognized for the impact of his foundational work to develop a new class of cancer immunotherapy treatment.”

Read the full story in Penn Today.

June is a member of the Penn Bioengineering Graduate Group. Read more stories featuring June on the BE Blog here.

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Carl June on the Boundless Potential of CAR T Cell Therapy

by Meagan Raeke

Carl June, at the flash mob celebration of the FDA approval of the CAR T cell therapy he developed, in August 2017. (Image: Courtesy of Penn Medicine Magazine)

For most of modern medicine, cancer drugs have been developed the same way: by designing molecules to treat diseased cells. With the advent of immunotherapy, that changed. For the first time, scientists engineered patients’ own immune systems to recognize and attack diseased cells.

One of the best examples of this pioneering type of medicine is CAR T cell therapy. Invented in the Perelman School of Medicine by Carl June, the Richard W. Vague Professor in Immunotherapy, CAR T cell therapy works by collecting T cells from a patient, modifying those cells in the lab so that they are designed to destroy cancerous cells, and reinfusing them into the patient. June’s research led to the first FDA approval for this type of therapy, in 2017. Six different CAR T cell therapies are now approved to treat various types of blood cancers. Carl June, at the flash mob celebration of the FDA approval of the CAR T cell therapy he developed, in August 2017. (Image: Courtesy of Penn Medicine Magazine)

CAR T cell therapy holds the potential to help millions more patients—if it can be successfully translated to other conditions. June and colleagues, including Daniel Baker, a fourth-year doctoral student in the Cell and Molecular Biology department, discuss this potential in a perspective published in Nature.

In the piece, June and Baker highlight other diseases that CAR T cell therapy could be effective.

“CAR T cell therapy has been remarkably successful for blood cancers like leukemias and lymphomas. There’s a lot of work happening here at Penn and elsewhere to push it to other blood cancers and to earlier stage disease, so patients don’t have to go through chemo first,” June says. “Another big priority is patients with solid tumors because they make up the vast majority of cancer patients. Beyond cancer, we’re seeing early signs that CAR T cell therapy could work in autoimmune diseases, like lupus.”

As for which diseases to pursue as for possible future treatment, June says, “essentially it boils down to two questions: Can we identify a population of cells that are bad? And can we target them specifically? Whether that’s asthma or chronic diseases or lupus, if you can find a bad population of cells and get rid of them, then CAR T cells could be therapeutic in that context.”

“What’s exciting is it’s not just theoretical at this point. There have been clinical reports in other autoimmune diseases, including myasthenia gravis and inflammatory myopathy,” Baker says. “But we are seeing early evidence that CAR T cell therapy will be successful beyond cancer. And it’s really opening the minds of people in the field to think about how else we could use CAR T. For example, there’s some pioneering work at Penn from the Epstein lab for heart failure. The idea is that you could use CAR T cells to get rid of fibrotic tissue after a cardiac injury, and potentially restore the damage following a heart attack.”

Baker adds, “there’s no question that over the last decade, CAR T cell therapy has revolutionized cancer. I’m hoping to play a role in bringing these next generation therapies to patients and make a real impact over the next decade. I think there’s potential for cell therapy to be a new pillar of medicine at large, and not just a new pillar of oncology.”

Read the full story at Penn Medicine Today.

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An Improved Delivery System for mRNA Vaccines Provides More Powerful Protection

by Devorah Fischler

(From left to right) Xuexiang Han, Michael Mitchell and Mohamad-Gabriel Alameh

The COVID-19 vaccine swiftly undercut the worst of the pandemic for hundreds of millions around the world. Available sooner than almost anyone expected, these vaccines were a triumph of resourcefulness and skill.

Messenger RNA vaccines, like the ones manufactured by Moderna or Pfizer/BioNTech, owed their speed and success to decades of research reinforcing the safety and effectiveness of their unique immune-instructive technology.

Now, researchers from the University of Pennsylvania School of Engineering and Applied Science and the Perelman School of Medicine are refining the COVID-19 vaccine, creating an innovative delivery system for even more robust protection against the virus.

In addition to outlining a more flexible and effective COVID-19 vaccine, this work has potential to increase the scope of mRNA vaccines writ large, contributing to prevention and treatment for a range of different illnesses.

Michael Mitchell, associate professor in Penn Engineering’s Department of Bioengineering, Xuexiang Han, postdoctoral fellow in Mitchell’s lab, and Mohamad-Gabriel Alameh, postdoctoral fellow in Drew Weissman’s lab at Penn Medicine and incoming assistant professor in the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine, recently published their findings in Nature Nanotechnology.

mRNA, or messenger ribonucleic acid, is the body’s natural go-between. mRNA contains the instructions our cells need to produce proteins that play important roles in our bodies’ health, including mounting immune responses.

The COVID-19 vaccines follow suit, sending a single strand of RNA to teach our cells how to recognize and fight the virus.

Read the full story in Penn Engineering Today.

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Chasing the Mysteries of Microbiome Communication in Our Bodies

by Kelsey Geesler

Perelman School of Medicine’s Maayan Levy, and Christoph Thaiss. (Image: Courtesy of Penn Medicine News)

When we hear about gut bacteria, we may think about probiotics and supplements marketed to help with digestion, about how taking antibiotics might affect our intestinal tract, or perhaps about trendy diets that aim to improve gut health.

But two researchers at Penn Medicine think that understanding the microbiome, the entirety of microbial organisms associated with the human body, might be the key to deciphering the fundamental mechanisms that make our bodies work. They think these microbes may work like a call center switchboard, making connections to help different organs, biological systems, and the brain communicate. Maayan Levy, and Christoph Thaiss, both assistant professors of microbiology at the Perelman School of Medicine, argue that the microbiome is instrumental to revealing how signals from the gastrointestinal tract are received by the rest of the body—which may hold the key to understanding inter-organ communication in general. Perelman School of Medicine’s Maayan Levy, and Christoph Thaiss. (Image: Courtesy of Penn Medicine News)

While the gut sends signals to all parts of the body to initiate various biological processes, the mechanisms underlying this communication—and communication between different organs involved in these processes—is relatively unknown.

“The more we learn about the role the microbiome plays in a wide range of diseases— from cancer to neurodegenerative diseases to inflammatory diseases—the more important it becomes to understand what exactly its role is,” says Thaiss. “And hopefully once we understand how it works, we can use the microbiome to treat these diseases.”

Levy and Thaiss joined the faculty at Penn Medicine after completing their graduate studies in 2018. Here, they continue to investigate the role of the microbiome in various biological processes.

In his lab, Thaiss focuses on the impact of the microbiome on the brain. He recently identified species of gut-dwelling bacteria that activate nerves in the gut to promote the desire to exercise. Most recently, Thaiss published a study that identified the cells that communicate psychological stress signals from the brain to the gastrointestinal tract, and cause symptoms of inflammatory bowel disease.

Meanwhile, in her lab, Levy examines how the microbiome influences the development of diseases, like cancer, and other conditions throughout the body.

A recent publication authored by Levy suggested that the ketogenic diet (high fat, low carbohydrate) causes the production of a metabolite called beta-hydroxybutyrate (BHB), that suppresses colorectal cancer in small animal models.

Now, Levy is collaborating with Bryson Katona, an assistant professor of Medicine in the division of gastroenterology who specializes in gastrointestinal cancers, to investigate whether BHB has the same effect in patients with Lynch syndrome, which causes individuals to have a genetic predisposition to many different kinds of cancer, including colon cancer. These efforts are part of a growing emphasis at Penn on finding methods to intercept cancer in its earliest stages.

“It’s remarkable that we were able to quickly take the findings from our animal models and rapidly design a clinical trial,” Levy says. “One of the most exciting aspects of our work is not only making discoveries about how our bodies work on a biological level, but then being able to work with the world’s leading clinical experts to translate these discoveries into therapies for patients.”

Further, studies led by Levy and Thaiss often utilize human samples and data from the Penn Medicine BioBank, to validate animal model findings in the tissue of human patients suffering from the diseases which they are investigating.

While Levy and Thaiss pursue different research interests with their labs, they also collaborate often, building on their previous research into what the microbiome does, and its role in the biological processes that keep us healthy. Their long-term goal is to learn about the mechanisms by which the gastrointestinal tract influences disease processes in other organs to treat various diseases of the body using the gastrointestinal tract as a noninvasive entry point to the body.

“Some of the most common and devastating diseases in humans—like cancer or neurodegeneration—are difficult to treat because they are no existing therapies that can reach the brain,” says Thaiss. “If we can understand how the gastrointestinal tract interacts with other organs in the body, including the brain, we might be able to develop treatments that ‘send messages’ to these organs through the body’s natural communication pathways.”

“Obviously there is a lot more basic biology to be uncovered before we get there,” adds Levy. “Most importantly, we want to map all the different routes by which the gastrointestinal tract interacts with the body, and how that communication happens.”

Read the full story in Penn Medicine News.

Christopher Thaiss is Assistant Professor in Microbiology in the Perelman School of Medicine. He is a member of the Penn Bioengineering Graduate Group.

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Penn Engineers Create Low-Cost, Eco-Friendly COVID Test

by Kat Sas

Fabrication steps of the biodegradable BC substrate and the electrochemical devices. (1) Incubation of the bacterium Gluconacetobacter hansenii. (2) BC substrate collected and treated, resulting in a clear sheet. (3) The biodegradable BC sheet is screen-printed, (4) resulting in a device with 3 electrodes, (4) which are cut out using a scissor, (5) resulting in a portable, biodegradable, and inexpensive electrochemical sensor.

The availability of rapid, accessible testing was integral to overcoming the worst surges of the COVID-19 pandemic, and will be necessary to keep up with emerging variants. However, these tests come with unfortunate costs.

Polymerase chain reaction (PCR) tests, the “gold standard” for diagnostic testing, are hampered by waste. They require significant time (results can take up to a day or more) as well as specialized equipment and labor, all of which increase costs. The sophistication of PCR tests makes them harder to tweak, and therefore slower to respond to new variants. They also carry environmental impacts. For example, most biosensor tests developed to date use printed circuit boards, or PCBs, the same materials used in computers. PCBs are difficult to recycle and slow to biodegrade, using large amounts of metal, plastic and non-eco-friendly materials.

In addition, most PCR tests end up in landfills, resulting in material waste and secondary contamination. An analysis by the World Health Organization (WHO) estimated that, as of February 2022, “over 140 million test kits, with a potential to generate 2,600 tonnes of non-infectious waste (mainly plastic) and 731,000 litres of chemical waste (equivalent to one-third of an Olympic-size swimming pool) have been shipped.”

In order to balance the need for fast, affordable and accurate testing while addressing these environmental concerns, César de la Fuente, Presidential Assistant Professor in Bioengineering and Chemical and Biomolecular Engineering in the School of Engineering and Applied Science, with additional primary appointments in Psychiatry and Microbiology within the Perelman School of Medicine, has turned his attention to the urgent need for “green” testing materials.

The de la Fuente lab has been working on creative ways to create faster and cheaper testing for COVID-19 since the outbreak of the pandemic. Utilizing his lab’s focus on machine biology and the treatment of infectious disease, they created RAPID, an aptly named test that generates results in minutes with a high degree of accuracy. An even more cost-effective version, called LEAD, was created using electrodes made from graphite. A third test, called COLOR, was a low-cost optodiagnostic test printed on cotton swabs.

The team’s latest innovation incorporates the speed and cost-effectiveness of previous tests with eco-friendly materials. In a paper published in Cell Reports Physical Science, the group introduces a new test made from Bacterial Cellulose (BC), an organic compound synthesized from several strains of bacteria, as a substitute for PCBs.

Read the full story in Penn Engineering Today.