Tag: Graduate Group

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The NEMO Prize Goes to Research Improving Soft-Tissue Transplant Surgeries

by Melissa Pappas

Daeyeon Lee (left), Oren Friedman (center) and Sergei Vinogradov (right)

Each year, the Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize, funded by Penn Health-Tech, awards $80,000 to a collaborative team of researchers from the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science for early-stage, interdisciplinary ideas.

This year, the NEMO Prize has been awarded to Penn Engineering’s Daeyeon Lee, Russel Pearce and Elizabeth Crimian Heuer Professor in Chemical and Biomolecular Engineering, Oren Friedman, Associate Professor of Clinical Otorhinolaryngology in the Perelman School of Medicine, and Sergei Vinogradov, Professor in the Department of Biochemistry and Biophysics in the Perelman School of Medicine and the Department of Chemistry in the School of Arts & Sciences. Together, they are developing a new therapy that improves the survival and success of soft-tissue grafts used in reconstructive surgery.

More than one million people receive soft-tissue reconstructive surgery for reasons such as tissue trauma, cancer or birth defects. Autologous tissue transplants are those where cells and tissue such as fat, skin or cartilage are moved from one part of a patient’s body to another. As the tissue comes from the patient, there is little risk of transplant rejection. However, nearly one in four autologous transplants fail due to tissue hypoxia, or lack of oxygen. When transplants fail the only corrective option is more surgery. Many techniques have been proposed and even carried out to help oxygenate soft tissue before it is transplanted to avoid failures, but current solutions are time consuming and expensive. Some even have negative side effects. A new therapy to help oxygenate tissue quickly, safely and cost-effectively would not only increase successful outcomes of reconstructive surgery, but could be widely applied to other medical challenges. 

The therapy proposed by this year’s NEMO Prize recipients is a conglomerate or polymer of microparticles that can encapsulate oxygen and disperse it in sustainable and controlled doses to specific locations over periods of time up to 72 hours. This gradual release of oxygen into the tissue from the time it is transplanted to the time it functionally reconnects to the body’s vascular system is essential to keeping the tissue alive. 

“The microparticle design consists of an oxygenated core encapsulated in a polymer shell that enables the sustained release of oxygen from the particle,” says Lee. “The polymer composition and thickness can be controlled to optimize the release rate, making it adaptable to the needs of the hypoxic tissue.” 

These life-saving particles are designed to be integrated into the tissue before transplantation. However, because they exist on the microscale, they can also be applied as a topical cream or injected into tissue after transplantation. 

“Because the microparticles are applied directly into tissues topically or by interstitial injection (rather than being administered intravenously), they surpass the need for vascular channels to reach the hypoxic tissue,” says Friedman. “Their micron-scale size combined with their interstitial administration, minimizes the probability of diffusion away from the injury site or uptake into the circulatory system. The polymers we plan to use are FDA approved for sustained-release drug delivery, biocompatible and biodegrade within weeks in the body, presenting minimal risk of side effects.”

The research team is currently testing their technology in fat cells. Fat is an ideal first application because it is minimally invasive as an injectable filler, making it versatile in remodeling scars and healing injury sites. It is also the soft tissue type most prone to hypoxia during transplant surgeries, increasing the urgency for oxygenation therapy in this particular tissue type.

Read the full story in Penn Engineering Today.

Daeyeon Lee and Sergei Vinogradov are members of the Penn Bioengineering Graduate Group.

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Penn Bioengineers Awarded 2023 “Accelerating from Lab to Market Pre-Seed” Grants

Congratulations to the members of the Penn Bioengineering community who were awarded 2023 Accelerating from Lab to Market Pre-Seed Grants from the University of Pennsylvania Office of the Vice Provost for Research (OVPR).

Andrew Tsourkas, Ph.D.

Three faculty affiliated with Bioengineering were included among the four winners. Andrew Tsourkas, Professor in Bioengineering and Co-Director of the Center for Targeted Therapeutics and Translational Nanomedicine (CT3N), was awarded for his project titled “Precise labeling of protein scaffolds with fluorescent dyes for use in biomedical applications.” Tsourkas’s team created protein scaffold that can better control the location and orientation of fluorescent dyes, commonly used for a variety of biomedical applications, such as labeling antibodies or fluorescence-guided surgery. The Tsourkas Lab specializes in “creating novel targeted imaging and therapeutic agents for the detection and/or treatment of diverse diseases.”

Also awarded were Penn Bioengineering Graduate Group members Mark Anthony Sellmeyer, Assistant Professor in Radiology in the Perelman School of Medicine, and Rahul M. Kohli, Associate Professor of Medicine in the Division of Infectious Diseases in the Perelman School of Medicine.

From the OVPR website:

“Penn makes significant commitments to academic research as one of its core missions, including investment in faculty research programs. In some disciplines, the path by which discovery makes an impact on society is through commercialization. Pre-seed grants are often the limiting step for new ideas to cross the ‘valley of death’ between federal research funding and commercial success. Accelerating from Lab to Market Pre-Seed Grant program aims to help to bridge this gap.”

Read the full list of winning projects and abstracts at the OVPR website.

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Combined Treatment Takes a Bite Out of Tooth Decay

by Nathi Magubane

Michel Koo of the School of Dental Medicine and David Cormode of the Perelman School of Medicine and the School of Engineering and Applied Science led a team of researchers that uncovered a way to combine two FDA-approved treatments to treat tooth decay that taps into the blend’s bacteria-killing capabilities without disrupting the mouth’s microbiome. (Image: iStock / Alex Sholom)

The sting of a toothache or the discovery of a cavity is a universal dread. Dental caries, more commonly known as tooth decay, is an insidious adversary, taking a toll on millions of mouths worldwide. Caries can lead to pain, tooth loss, infection, and, in severe cases, even death.

While fluoride-based treatments have long been the gold standard in dentistry, this singular approach is now dated and has limited effect. Current treatments do not sufficiently control biofilm—the main culprit behind dental caries—and prevent enamel demineralization at the same time. This dual dilemma becomes particularly pronounced in high-risk populations where the onset of the disease can be both rapid and severe.

Now, a study from a team of researchers led by Hyun (Michel) Koo of the University of Pennsylvania’s School of Dental Medicine in collaboration with David Cormode of Penn’s Perelman School of Medicine and School of Engineering and Applied Science has unveiled an unexpected synergy in the battle against dental caries. Their research revealed that the combination of ferumoxytol (Fer) and stannous fluoride (SnF2) could point at a potent solution against dental caries. Their findings were published in Nature Communications.

“Traditional treatments often come short in managing the complex biofilm environment in the mouth,” Koo, senior co-author on the study, says. “Our combined treatment not only amplifies the effectiveness of each agent but does so with a lower dosage, hinting at a potentially revolutionary method for caries prevention in high-risk individuals.”

Read the full story in Penn Today.

Hyun (Michel) Koo is a professor in the Department of Orthodontics and in the divisions of Pediatric Dentistry and Community Oral Health and the co-founder of the Center for Innovation & Precision Dentistry in the School of Dental Medicine at the University of Pennsylvania. He is a member of the Penn Bioengineering Graduate Group.

David Cormode is an associate professor of radiology and bioengineering with appointments in Penn’s Perelman School of Medicine and School of Engineering and Applied Science.

Other authors are Yue Huang, Nil Kanatha Pandey, Shrey Shah, and Jessica C. Hsu of Penn’s Perelman School of Medicine; Yuan Liu, Aurea Simon-Soro, Zhi Ren, Zhenting Xiaang, Dongyeop Kim, Tatsuro Ito, Min Jun Oh, and Yong Li of Penn’s School of Dental Medicine; Paul. J Smeets, Sarah Boyer, Xingchen Zhao, and Derk Joester of Northwestern University; and Domenick T. Zero of Indiana University.

The work was supported by the National Institute of Health (grants R01-DE025848 and TL1TR001423 and awards S10OD026871 and R90DE031532) and the National Science Foundation (awards ECCS-2025633 and DMR-1720139).

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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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How the Hippocampus Distinguishes True and False Memories

by Erica Moser

Image: iStock/metamorworks

Let’s say you typically eat eggs for breakfast but were running late and ate cereal. As you crunched on a spoonful of Raisin Bran, other contextual similarities remained: You ate at the same table, at the same time, preparing to go to the same job. When someone asks later what you had for breakfast, you incorrectly remember eating eggs.

This would be a real-world example of a false memory. But what happens in your brain before recalling eggs, compared to what would happen if you correctly recalled cereal?

In a paper published in Proceedings of the National Academy of Sciences, University of Pennsylvania neuroscientists show for the first time that electrical signals in the human hippocampus differ immediately before recollection of true and false memories. They also found that low-frequency activity in the hippocampus decreases as a function of contextual similarity between a falsely recalled word and the target word.

“Whereas prior studies established the role of the hippocampus in event memory, we did not know that electrical signals generated in this region would distinguish the imminent recall of true from false memories,” says psychology professor Michael Jacob Kahana, director of the Computational Memory Lab and the study’s senior author. He says this shows that the hippocampus stores information about an item with the context in which it was presented.

Researchers also found that, relative to correct recalls, the brain exhibited lower theta and high-frequency oscillations and higher alpha/beta oscillations ahead of false memories. The findings came from recording neural activity in epilepsy patients who were already undergoing invasive monitoring to pinpoint the source of their seizures.

Noa Herz, lead author and a postdoctoral fellow in Kahana’s lab at the time of the research, explains that the monitoring was done through intracranial electrodes, the methodology researchers wanted to use for this study. She says that, compared to scalp electrodes, this method “allowed us to more precisely, and directly, measure the neural signals that were generated in deep brain structures, so the activity we are getting is much more localized.”

Read the full story in Penn Today.

Michael Kahana is the Edmund J. and Louise W. Kahn Term Professor of Psychology in the School of Arts & Sciences and director of the Computational Memory Lab at the University of Pennsylvania. He is a member of the Penn Bioengineering Graduate Group.

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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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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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Student Spotlight: Cosette Tomita

Cosette TomitaCosette Tomita, a master’s student in Bioengineering, spoke with Penn Engineering Graduate Admissions about her research in cellular therapy and her path to Penn Engineering.

“What were you doing before you came to Penn Engineering? 

After college I wanted to get some industry experience before going to graduate school, so I spent a year working for a pharmaceutical company in New Jersey. I learned a lot—but mostly I learned that I wanted to go back into academia. So I was looking for a more research-oriented position to boost my graduate school applications, and I found a position at Penn’s cyclotron facility. Shortly after that, I applied to the master’s program. I’m still working at the cyclotron, so I’m doing the program part time. 

How has your experience in the program been so far? 

I love the research I’m doing here. I love the collaboration we have and the fact that I’m able to work with whoever I want to. And I can only say good things about my PI, Robert Mach. He’s a very busy man, but he makes time for his people. And he recognizes when somebody has a lot on their plate and he will go to bat for that person.

What’s your research all about? 

The focus of my PI’s lab is on neurodegenerative diseases and opiate use, so we’re looking to make imaging agents and antagonists that can help with the opioid crisis. 

For my project, I wanted to look at treating neurodegenerative disease from the perspective of cellular therapy. My PI doesn’t have that expertise, so when I came to him with this idea, he said I should talk to Mark Sellmyer in the bioengineering department. He does a lot of cellular therapies, cell engineering, protein engineering and things of that nature. So his lab is more biological. 

I don’t have a grant for my research, so my advisors are supporting it out of their own pockets. They could have said, no, you need to work on this project that’s already going on in the lab. But they gave me the intellectual freedom to do what I wanted to do.”

Read the full Q&A at the Penn Engineering Graduate Admissions website.

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