César de la Fuente Named ELHM Scholar by National Academy of Medicine

César de la Fuente, Ph.D.

César de la Fuente, Presidential Assistant Professor in Bioengineering, Psychiatry, Microbiology, and in Chemical and Biomolecular Engineering, has been selected as a 2023 Emerging Leaders in Health and Medicine (ELHM) Scholar by the National Academy of Medicine (NAM). With joint appointments in both Penn Engineering and the Perelman School of Medicine, de la Fuente works to combine human and machine intelligence to accelerate scientific discovery and develop useful tools and life-saving medicines.

NAM, founded in 1970, is an independent organization of professionals that advises the entire scientific community on critical health care issues. Each year, NAM chooses up to 10 new ELHM Scholars who are early-to-mid-career professionals from a wide range of health-related fields, including biomedical engineering, internal medicine, psychiatry, radiology and journalism to serve a three-year term.

“We are delighted that Dr. de la Fuente is receiving recognition from the National Academy of Medicine for his breakthrough contributions and exceptional leadership in the life sciences,” says Vijay Kumar, Nemirovsky Family Dean of Penn Engineering. “His pioneering work using computers to accelerate antibiotic discovery is extraordinary. We proudly celebrate his selection as part of this outstanding group of scholars.”

Read the full story in Penn Engineering Today.

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.

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.

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.

For a New Generation of Antibiotics, Scientists are Bringing Extinct Molecules Back to Life – and Discovering the Hidden Genetics of Immunity Along the Way

by Devorah Fischler

Marrying artificial intelligence with advanced experimental methods, the Machine Biology Group has mined the ancient past for future medical breakthroughs, bringing extinct molecules back to life. (Image credit: Ella Marushchenko)

“We need to think big in antibiotics research,” says Cesar de la Fuente. “Over one million people die every year from drug-resistant infections, and this is predicted to reach 10 million by 2050. There hasn’t been a truly new class of antibiotics in decades, and there are so few of us tackling this issue that we need to be thinking about more than just new drugs. We need new frameworks.”

De la Fuente is Presidential Assistant Professor in the Department of Bioengineering and the Department of Chemical and Biomolecular Engineering at the University of Pennsylvania School of Engineering and Applied Science. He holds additional primary appointments in Psychiatry and Microbiology in the Perelman School of Medicine.

De la Fuente’s lab, the Machine Biology Group, creates these new frameworks using potent partnerships in engineering and the health sciences, drawing on the “power of machines to accelerate discoveries in biology and medicine.”

Marrying artificial intelligence with advanced experimental methods, the group has mined the ancient past for future medical breakthroughs. In a recent study published in Cell Host and Microbe, the team has launched the field of “molecular de-extinction.”

Our genomes – our genetic material – and the genomes of our ancient ancestors, express proteins with natural antimicrobial properties. “Molecular de-extinction” hypothesizes that these molecules could be prime candidates for safe new drugs. Naturally produced and selected through evolution, these molecules offer promising advantages over molecular discovery using AI alone.

In this paper, the team explored the proteomic expressions of two extinct organisms –Neanderthals and Denisovans, archaic precursors to the human species – and found dozens of small protein sequences with antibiotic qualities. Their lab then worked to synthesize these molecules, bringing these long-since-vanished chemistries back to life.

“The computer gives us a sequence of amino acids,” says de la Fuente. “These are the building blocks of a peptide, a small protein. Then we can make these molecules using a method called ‘solid-phase chemical synthesis.’ We translate the recipe of amino acids into an actual molecule and then build it.”

The team next applied these molecules to pathogens in a dish and in mice to test the veracity and efficacy of their computational predictions.

“The ones that worked, worked quite well,” continues de la Fuente. “In two cases, the peptides were comparable – if not better – than the standard of care. The ones that didn’t work helped us learn what needed to be improved in our AI tools. We think this research opens the door to new ways of thinking about antibiotics and drug discovery, and this first step will allow scientists to explore it with increasing creativity and precision.”

Read the full story in Penn Engineering Today.

Artificial Intelligence is Leveling Up the Fight Against Infectious Diseases

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Image credit: NIAID

Artificial intelligence is a new addition to the infectious disease researcher’s toolbox. Yet in merely half a decade, AI has accelerated progress on some of the most urgent issues in medical science and public health. Researchers in this field blend knowledge of life sciences with skill in computation, chemistry and design, satisfying decades-long appeals for interdisciplinary tactics to treat these disorders and stop their spread.

Diseases are “infectious” when they are caused by organisms, including parasites, viruses, bacteria and fungi. People and animals can contract infectious diseases from their environments or food, or through interactions with one another. Some, but not all, are contagious.

Infectious diseases are an intractable global challenge, posing problems that continue to grow in severity even as science has offered a steady pace of solutions. The world continues to become more interconnected, bringing people into new kinds and levels of relation, and the climate crisis is throwing environmental and ecological networks out of balance. Diseases that were once treatable by drugs have become resistant, and new drug discovery is more costly than ever. Uneven resource distribution means that certain parts of the world are perennial hotspots for diseases that others never fear.

Cesar de la Fuente brings an expert eye to how AI has transformed infectious disease research in a recently published piece in Science with co-authors Felix Wong and James J. Collins from MIT.

Presidential Assistant Professor in the Department of Bioengineering and the Department of Chemical and Biomolecular Engineering at the University of Pennsylvania School of Engineering and Applied Science, with additional primary appointments in Psychiatry and Microbiology within the Perelman School of Medicine, de la Fuente brings a multifaceted perspective to his survey of the field.

In the paper, de la Fuente and co-authors assess the progress, limitations and promise of research in AI and infectious diseases in three major areas of inquiry: anti-infective drug discovery, infection biology, and diagnostics for infectious diseases.

Read more in Penn Engineering Today.

César de la Fuente Receives 2023 Rao Makineni Lectureship Award

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César de la Fuente
César de la Fuente

The American Peptide Society has selected César de la Fuente, Presidential Assistant Professor in Psychiatry, Microbiology, Bioengineering and in Chemical and Biomolecular Engineering, as the recipient of the prestigious 2023 Rao Makineni Lectureship Award.

Presented at the biennial American Peptide Symposium, the Makineni Lectureship Award recognizes an individual who has made a recent contribution of unusual merit to research in the field of peptide science, and is intended to acknowledge original and singular discoveries.

Established in 2003 by an endowment by PolyPeptide Laboratories and Murray and Zelda Goodman, this lectureship honors Rao Makineni, a long-time supporter of peptide science, peptide scientists, and the American Peptide Society.

This story originally appeared in Penn Engineering Today.

Cesar de la Fuente On the “Next Frontier” of Antibiotics

César de la Fuente
César de la Fuente

In a recent CNN feature, César de la Fuente, Presidential Assistant Professor in Bioengineering, Psychiatry, Microbiology, and in Chemical and Biomolecular Engineering commented on a study about a new type of antibiotic that was discovered with artificial intelligence:

“I think AI, as we’ve seen, can be applied successfully in many domains, and I think drug discovery is sort of the next frontier.”

The de la Fuente lab uses machine learning and biology to help prevent, detect, and treat infectious diseases, and is pioneering the research and discovery of new antibiotics.

Read “A new antibiotic, discovered with artificial intelligence, may defeat a dangerous superbug” in CNN Health.

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

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

Margaret Billingsley

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

Maggie Billingsley

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

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

Victoria Muir

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

Victoria Muir

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

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

Sadhana Ravikumar 

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

Sadhana Ravikumar

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

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

Hannah Zlotnick

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

Hannah Zlotnick

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

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

Congratulations to our four amazing 2023 Sol Pollack Award winners!

César de la Fuente Named AIMBE Fellow

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César de la Fuente
César de la Fuente

César de la Fuente, Presidential Assistant Professor in Psychiatry, Microbiology, Bioengineering and in Chemical and Biomolecular Engineering, has been named an American Institute for Medical and Biological Engineering (AIMBE) Fellow. The only faculty member inducted this year from the University of Pennsylvania, de la Fuente is one of the youngest members ever to have been selected as an AIMBE Fellow.

Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer, with AIMBE Fellows representing the top 2% of medical and biological engineers. College membership honors those who have made outstanding contributions to “engineering and medicine research, practice, or education” and to “the pioneering of new and developing fields of technology, making major advancements in traditional fields of medical and biological engineering, or developing/implementing innovative approaches to bioengineering education.”

Nominated and reviewed by peers and members of the College of Fellows, de la Fuente was elected Fellow “for the development of novel antimicrobial peptides designed using principles from computation, engineering and biology.”

A formal ceremony will be held during the AIMBE Annual Event in Arlington, Virginia on March 27, 2023, where de la Fuente will be inducted along with 140 colleagues who make up the AIMBE College of Fellows Class of 2023.

AIMBE Fellows are among the most distinguished medical and biological engineers, including 3 Nobel Prize laureates and 17 Fellows having received the Presidential Medal of Science and/or Technology and Innovation, along with 205 having been inducted into the National Academy of Engineering, 105 into the National Academy of Medicine and 43 into the National Academy of
Sciences.

This story was originally posted in Penn Engineering Today.

Read more stories featuring César de la Fuente here.