Joseph Lance Casila, a doctoral student and Fontaine Fellow in Bioengineering, was profiled by his alma mater, the University of Guam (UOG. Casila was the first person in his family to graduate from a U.S.-accredited university and is now studying tissue engineering and regenerative medicine in the Bioengineering and Biomaterials Laboratory of Riccardo Gottardi, Assistant Professor in Bioengineering in Penn Engineering and Pediatrics in Penn Medicine and the Children’s Hospital of Philadelphia (CHOP). His research in the Gottardi lab employs “tissue engineering and drug delivery for biomedical problems relating to knees, ears, nose, and throat but specifically to pediatric airway disorders.” The article discusses Casila’s journey from valedictorian of his high school, to a first-generation undergraduate interested bioengineering, and now a graduate student studying at Penn on a full scholarship. After completing his degree, Casila hopes to bring what he’s learned back home to advance health care in Guam.
“My mentors, and especially my friends, helped me make the most of what UOG had to offer, and it paid off rewardingly,” he said. “You get what you put in.”
Yogesh Goyal, Ph.D., a postdoctoral researcher in Genetics and Bioengineering, has been selected as a 2021 STAT Wunderkind, which honors the “next generation of scientific superstars.” Goyal’s research is centered around developing novel mathematical and experimental frameworks to study how a rare subpopulation of cancer cells are able to survive drug therapy and develop resistance, resulting in relapse in patients. In particular, his work provides a view of different paths that single cancer cells take when becoming resistant, at unprecedented resolution and scale. This research aims to help devise novel therapeutic strategies to combat the challenge of drug resistance in cancer.
Goyal is a Jane Coffin Childs Postdoctoral Fellow in the systems biology lab of Arjun Raj, Professor in Bioengineering and Genetics at Penn. He will begin an appointment as Assistant Professor in the Department of Cell and Developmental Biology (CDB) in the Feinberg School of Medicine at Northwestern University in spring 2022.
While biologists and chemists race to develop new antibiotics to combat constantly mutating bacteria, predicted to lead to 10 million deaths by 2050, engineers are approaching the problem through a different lens: finding naturally occurring antibiotics in the human genome.
The billions of base pairs in the genome are essentially one long string of code that contains the instructions for making all of the molecules the body needs. The most basic of these molecules are amino acids, the building blocks for peptides, which in turn combine to form proteins. However, there is still much to learn about how — and where — a particular set of instructions are encoded.
Now, bringing a computer science approach to a life science problem, an interdisciplinary team of Penn researchers have used a carefully designed algorithm to discover a new suite of antimicrobial peptides, hiding deep within this code.
The study, published in Nature Biomedical Engineering, was led by César de la Fuente, Presidential Assistant Professor in Bioengineering, Microbiology, Psychiatry, and Chemical and Biomolecular Engineering, spanning both Penn Engineering and Penn Medicine, and his postdocs Marcelo Torres and Marcelo Melo. Collaborators Orlando Crescenzi and Eugenio Notomista of the University of Naples Federico II also contributed to this work.
“The human body is a treasure trove of information, a biological dataset. By using the right tools, we can mine for answers to some of the most challenging questions,” says de la Fuente. “We use the word ‘encrypted’ to describe the antimicrobial peptides we found because they are hidden within larger proteins that seem to have no connection to the immune system, the area where we expect to find this function.”
Catherine Michelutti (SEAS/WHARTON ’23) working on her internship in her backyard with her dog
Catherine Michelutti, a junior in Bioengineering and Wharton and fellow in the Stavros Niarchos Foundation (SNF) Paideia Program, shared her virtual internship experience with the Orion Organisation, a healthcare NGO based in South Africa that provides for “the educational, training and therapeutic needs of children, youth and adults living with physical, psychosocial challenges, intellectual and neurological disabilities”:
“My internship with the Orion Organization has prompted me to reflect on my identity in terms of where my passions and future career interests lie. My previous work experiences have all been in biomedical research fields, which is something I’m passionate about and want to continue doing throughout my career. However, working with Orion has opened my eyes to the realms of interdisciplinary work that comes with operating a healthcare NGO and the joys that come with it.”
Speaker: Ilana Lauren Brito, Ph.D.
Assistant Professor, Mong Family Sesquicentennial Faculty Fellow in Biomedical Engineering
Meinig School of Biomedical Engineering
Cornell University
Date: Thursday, October 28, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Room: Moore 216
Abstract: A major question regarding the human gut microbiota is: by what mechanisms do our most intimately associated organisms affect human health? In this talk, I will present several systems-level approaches that we have developed to address this fundamental question. My lab has pioneered methods that leverage protein-protein interactions to implicate bacterial proteins in human pathways linked to disease, revealing for the first time a network of interactions that affect diseases such as colorectal cancer, inflammatory bowel disease, type 2 diabetes and obesity that can be mined for novel therapeutics and therapeutic targets. I will present novel methods that that enable deeper insight into the transcriptome of organisms within our guts and their spatial localization. Finally, I will shift to the problem of the spread of antibiotic resistance, in which the gut microbiota are implicated. Pathogens become multi-drug resistance by acquiring resistance traits carried by the gut microbiota. Studying this process in microbiomes is inherently difficult using current methods. I will present several methods that enable tracking of genes within the microbiome and computational tools that predict the network of gene transfer between bacteria. Overall, these systems-level tools provide deep insight into the knobs we can turn to engineer outcomes within the microbiome that can improve human health.
Ilana Brito Bio: Ilana Brito is an Assistant Professor of Biomedical Engineering at Cornell University. Ilana received a BA from Harvard and a PhD from MIT. She started her postdoc as an Earth Institute Postdoctoral Fellow at Columbia University where she launched the Fiji Community Microbiome Project, a study aimed at tracking microbiota across people and their social networks, and continued this work at MIT and the Broad Institute working with Eric Alm. In her lab at Cornell, Ilana and her team are developing a suite of experimental systems biology tools to probe the functions of the human microbiome in a robust, high-throughput manner. Ilana has received numerous accolades for her work, including a Sloan Research Fellowship, Packard Fellowship, a Pew Biomedical Research Scholarship and an NIH New Innovator Award.
Scientific American recently featured two gene therapies that were invented at Penn, including research from Carl June, MD, the Richard W. Vague Professor in Immunotherapy in Pathology and Laboratory Medicine, director of the Center for Cellular Immunotherapies, and member of the Penn Bioengineering Graduate Group, which led to the FDA approval for the CAR T therapy (sold by Novartis as Kymriah) for treating acute lymphoblastic leukemia (ALL), one of the most common childhood cancers.
A cross-disciplinary Penn team is pioneering a new approach to peripheral nerve repair.
In a new publication in the journal npjRegenerative Medicine, a team of Penn researchers from the School of Dental Medicine and the Perelman School of Medicine “coaxed human gingiva-derived mesenchymal stem cells (GMSCs) to grow Schwann-like cells, the pro-regenerative cells of the peripheral nervous system that make myelin and neural growth factors,” addressing the need for regrowing functional nerves involving commercially-available scaffolds to guide nerve growth. The study was led by Anh Le, Chair and Norman Vine Endowed Professor of Oral Rehabilitation in the Department of Oral and Maxillofacial Surgery/Pharmacology at the University of Pennsylvania School of Dental Medicine, and was co-authored by D. Kacy Cullen, Associate Professor in Neurosurgery at the Perelman School of Medicine at Penn and the Philadelphia Veterans Affairs Medical Center and member of the Bioengineering Graduate Group:
D. Kacy Cullen (Image: Eric Sucar)
“To get host Schwann cells all throughout a bioscaffold, you’re basically approximating natural nerve repair,” Cullen says. Indeed, when Le and Cullen’s groups collaborated to implant these grafts into rodents with a facial nerve injury and then tested the results, they saw evidence of a functional repair. The animals had less facial droop than those that received an “empty” graft and nerve conduction was restored. The implanted stem cells also survived in the animals for months following the transplant.
“The animals that received nerve conduits laden with the infused cells had a performance that matched the group that received an autograft for their repair,” he says. “When you’re able to match the performance of the gold-standard procedure without a second surgery to acquire the autograft, that is definitely a technology to pursue further.”
Read the full story and view the full list of collaborators in Penn Today.
A colorized microscope image of an osteosarcoma shows how cellular fibers can transfer physical force between neighboring nuclei, influencing genes. The Penn Anti-Cancer Engineering Center will study such forces, looking for mechanisms that could lead to new treatments or preventative therapies.
Advances in cell and molecular technologies are revolutionizing the treatment of cancer, with faster detection, targeted therapies and, in some cases, the ability to permanently retrain a patient’s own immune system to destroy malignant cells.
However, there are fundamental forces and associated challenges that determine how cancer grows and spreads. The pathological genes that give rise to tumors are regulated in part by a cell’s microenvironment, meaning that the physical push and pull of neighboring cells play a role alongside the chemical signals passed within and between them.
The Penn Anti-Cancer Engineering Center (PACE) will bring diverse research groups from the School of Engineering and Applied Science together with labs in the School of Arts & Sciences and the Perelman School of Medicine to understand these physical forces, leveraging their insights to develop new types of treatments and preventative therapies.
The Center’s founding members are Dennis Discher, Robert D. Bent Professor with appointments in the Departments of Chemical and Biomolecular Engineering (CBE), Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM), and Ravi Radhakrishnan, Professor and chair of BE with an appointment in CBE.
Discher, an expert in mechanobiology and in delivery of cells and nanoparticles to solid tumors, and Radhakrishnan, an expert on modeling physical forces that influence binding events, have long collaborated within the Physical Sciences in Oncology Network. This large network of physical scientists and engineers focuses on cancer mechanisms and develops new tools and trainee opportunities shared across the U.S. and around the world.
Lukasz Bugaj, Alex Hughes, Jenny Jiang, Bomyi Lim, Jennifer Lukes and Vivek Shenoy (Clockwise from upper left).
Among the PACE Center’s initial research efforts are studies of the genetic and immune mechanisms associated with whether a tumor is solid or liquid and investigations into how physical stresses influence cell signaling.
Jennifer E. Phillips-Cremins (upper left) and members of her lab.
Each year, the National Institutes of Health (NIH) recognizes exceptionally creative scientists through its High-Risk, High-Reward Research Program. The four awards granted by this program are designed to support researchers whose “out of the box” and “trailblazing” ideas have the potential for broad impact.
Jennifer E. Phillips-Cremins, Associate Professor and Dean’s Faculty Fellow in Penn Engineering’s Department of Bioengineering and the Perelman School of Medicine’s Department of Genetics, is one such researcher. As a recipient of an NIH Director’s Pioneer Award, she will receive $3.5 million over five years to support her work on the role that the physical folding of chromatin plays in the encoding of neural circuit and synapse properties contributing to long-term memory.
Phillips-Cremins’ award is one of 106 grants made through the High-Risk, High-Reward program this year, though she is only one of 10 to receive the Pioneer Award, which is the program’s largest funding opportunity.
“The science put forward by this cohort is exceptionally novel and creative and is sure to push at the boundaries of what is known,” said NIH Director Francis S. Collins.
Phillips-Cremins’ research is in the general field of epigenetics, the molecular and structural modifications that allow the genome — an identical copy of which is found in each cell — to express genes differently at different times and in different parts of the body. Within this field, her lab focuses on higher-order folding patterns of the DNA sequence, which bring distant sets of genes and regulatory elements into close proximity with one another as they are compressed inside the cell’s nucleus.
Previous work from the Cremins lab has investigated severe genome misfolding patterns common across a class of genetic neurological disorders, including fragile X syndrome, Huntington’s disease, ALS and Friedreich’s ataxia.
With the support of the Pioneer Award, she and the members of her lab will extend that research to a more fundamental question of neuroscience: how memory is encoded over decades, despite the rapid turnover of the relevant proteins and RNA sequences within the brain’s synapses.
“Our long-term goals are to understand how, when and why pathologic genome misfolding leads to synaptic dysfunction by way of disrupted gene expression,” said Phillips-Cremins, “as well as to engineer the genome’s structure-function relationship to reverse pathologic synaptic defects in debilitating neurological diseases.”
The Center for Precision Engineering for Health will bring together researchers spanning multiple scientific fields to develop novel therapeutic biomaterials, such as a drug-delivering nanoparticles that can be designed to adhere to only to the tissues they target. (Image: Courtesy of the Mitchell Lab)
The University of Pennsylvania announced today that it has made a $100 million commitment in its School of Engineering and Applied Science to establish the Center for Precision Engineering for Health.
The Center will conduct interdisciplinary, fundamental, and translational research in the synthesis of novel biomolecules and new polymers to develop innovative approaches to design complex three dimensional structures from these new materials to sense, understand, and direct biological function.
“Biomaterials represent the ‘stealth technology’ which will create breakthroughs in improving health care and saving lives,” says Penn President Amy Gutmann. “Innovation that combines precision engineering and design with a fundamental understanding of cell behavior has the potential to have an extraordinary impact in medicine and on society. Penn is already well established as an international leader in innovative health care and engineering, and this new Center will generate even more progress to benefit people worldwide.”
Penn Engineering will hire five new President’s Penn Compact Distinguished Professors, as well as five additional junior faculty with fully funded faculty positions that are central to the Center’s mission. New state-of-the-art labs will provide the infrastructure for the research. The Center will seed grants for early-stage projects to foster advances in interdisciplinary research across engineering and medicine that can then be parlayed into competitive grant proposals.
“Engineering solutions to problems within human health is one of the grand challenges of the discipline,” says Vijay Kumar, Nemirovsky Family Dean of Penn Engineering. “Our faculty are already leading the charge against these challenges, and the Center will take them to new heights.”
This investment represents a turning point in Penn’s ability to bring creative, bio-inspired approaches to engineer novel behaviors at the molecular, cellular, and tissue levels, using biotic and abiotic matter to improve the understanding of the human body and to develop new therapeutics and clinical breakthroughs. It will catalyze integrated approaches to the modeling and computational design of building blocks of peptides, proteins, and polymers; the synthesis, processing, and fabrication of novel materials; and the experimental characterizations that are needed to refine approaches to design, processing, and synthesis.
“This exciting new initiative,” says Interim Provost Beth Winkelstein, “brings together the essential work of Penn Engineering with fields across our campus, especially in the Perelman School of Medicine. It positions Penn for global leadership at the convergence of materials science and biomedical engineering with innovative new techniques of simulation, synthesis, assembly, and experimentation.”
Examples of the types of work being done in this field include new nanoparticle technologies to improve storage and distribution of vaccines, such as the COVID-19 mRNA vaccines; the development of protocells, which are synthetic cells that can be engineered to do a variety of tasks, including adhering to surfaces or releasing drugs; and vesicle based liquid biopsy for diagnosing cancer.
Beth Winkelstein is the Eduardo D. Glandt President’s Distinguished Professor in Bioengineering.
The featured illustration comes from a recent study led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering, and Margaret Billingsley, a graduate student in his lab.
