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.
In a new publication in the journal npj Regenerative 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:
“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.
by Evan Lerner
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.
Supported by a series of grants from the NIH’s National Cancer Institute, the PACE Center is Penn’s new hub within the Physical Sciences in Oncology Network. It will draw upon Penn’s ecosystem of related research, including faculty members from the Abramson Cancer Center, Center for Targeted Therapeutics and Translational Nanomedicine, Center for Soft and Living Matter, Institute for Regenerative Medicine, Institute for Immunology and Center for Genome Integrity.
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.
Additional Engineering faculty with growing efforts in the new Center include Lukasz Bugaj, Alex Hughes and Jenny Jiang (BE), Bomyi Lim (CBE), Jennifer Lukes (MEAM) and Vivek Shenoy (Materials Science and Engineering).
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.
Originally posted in Penn Engineering Today.
by Evan Lerner
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.”
Originally posted in Penn Engineering Today.
by Erica K. Brockmeier
New research published in Physical Review Letters describes how electrons move through two different configurations of bilayer graphene, the atomically-thin form of carbon. This study, the result of a collaboration between Brookhaven National Laboratory, the University of Pennsylvania, the University of New Hampshire, Stony Brook University, and Columbia University, provides insights that researchers could use to design more powerful and secure quantum computing platforms in the future.
“Today’s computer chips are based on our knowledge of how electrons move in semiconductors, specifically silicon,” says first and co-corresponding author Zhongwei Dai, a postdoc at Brookhaven. “But the physical properties of silicon are reaching a physical limit in terms of how small transistors can be made and how many can fit on a chip. If we can understand how electrons move at the small scale of a few nanometers in the reduced dimensions of 2-D materials, we may be able to unlock another way to utilize electrons for quantum information science.”
When a material is designed at these small scales, to the size of a few nanometers, it confines the electrons to a space with dimensions that are the same as its own wavelength, causing the material’s overall electronic and optical properties to change in a process called quantum confinement. In this study, the researchers used graphene to study these confinement effects in both electrons and photons, or particles of light.
The work relied upon two advances developed independently at Penn and Brookhaven. Researchers at Penn, including Zhaoli Gao, a former postdoc in the lab of Charlie Johnson who is now at The Chinese University of Hong Kong, used a unique gradient-alloy growth substrate to grow graphene with three different domain structures: single layer, Bernal stacked bilayer, and twisted bilayer. The graphene material was then transferred onto a special substrate developed at Brookhaven that allowed the researchers to probe both electronic and optical resonances of the system.
“This is a very nice piece of collaborative work,” says Johnson. “It brings together exceptional capabilities from Brookhaven and Penn that allow us to make important measurements and discoveries that none of us could do on our own.”
Read the full story in Penn Today.
Charlie Johnson is the Rebecca W. Bushnell Professor of Physics and Astronomy in the Department of Physics and Astronomy in the School of Arts & Sciences at the University of Pennsylvania and a member of the Penn Bioengineering Graduate Group.
by Erica K. Brockmeier
Rebecca Kamen, Penn artist-in-residence and visiting scholar, has long been interested in science and the natural world. As a Philadelphia native and an artist with a 40-plus-year career, her intersectional work sheds light on the process of scientific discovery and its connections to art, with previous exhibitions that celebrate Apollo 11’s “spirit of exploration and discovery” to new representations of the periodic table of elements.
Now, in her latest exhibition, Kamen has created a series of pieces that highlight how the creative processes in art and science are interconnected. In “Reveal: The Art of Reimagining Scientific Discovery,” Kamen chronicles her own artistic process while providing a space for self-reflection that enables viewers to see the relationship between science, art, and their own creativity.
The exhibit, on display at the Katzen Art Center at American University, was inspired by the work of Penn professor Dani Bassett and American University professor Perry Zurn, the exhibit’s faculty sponsor. The culmination of three years of work, “Reveal” features collaborations with a wide range of scientists, including philosophers at American University, microscopists at the National Institutes of Health studying SARS-CoV-2 , and researchers in Penn’s Complex Systems Lab and the Addiction, Health, and Adolescence (AHA!) Lab.
Continue reading at Penn Today.
Dani S. Bassett is the J. Peter Skirkanich Professor in the departments of Bioengineering and Electrical and Systems Engineering in the School of Engineering and Applied Science at the University of Pennsylvania. She also has appointments in the Department of Physics and Astronomy in Penn’s School of Arts & Sciences and the departments of Neurology and Psychiatry in the Perelman School of Medicine at Penn.
“Reveal: The Art of Reimagining Scientific Discovery,” presented by the Alper Initiative for Washington Art and curated by Sarah Tanguy, is on display at the American University Museum in Washington, D.C., until Dec. 12.
The exhbition catalog, which includes an essay on “Radicle Curiosity” by Perry Zurn and Dani S. Bassett, can be viewed online.
by Evan Lerner
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.
N.B.: This story originally appeared in Penn Engineering Today.
Beth Winkelstein is the Eduardo D. Glandt President’s Distinguished Professor in Bioengineering.
Thomas A.V. Cassel, Practice Professor in Mechanical Engineering and Applied Mechanics in the School of Engineering and Applied Science, recently sat down with Dayo Adetu (BSE 2019, MSE 2021), President of the Penn Graduate Association of Bioengineers (GABE), to give his insight into engineering entrepreneurship. Cassel is the Director of Penn’s Engineering Entrepreneurship Program, which he founded twenty one years ago. He joined Penn’s faculty in 1999 following a 20-year career of entrepreneurial business leadership.
Watch the video to hear about Cassel’s favorite Penn memories, the day-to-day experience of working at a startup, advice for venturing into entrepreneurship, and more.
by Melissa Pappas
COVID-19 vaccines are just the beginning for mRNA-based therapies; enabling a patient’s body to make almost any given protein could revolutionize care for other viruses, like HIV, as well as various cancers and genetic disorders. However, because mRNA molecules are very fragile, they require extremely low temperatures for storage and transportation. The logistical challenges and expense of maintaining these temperatures must be overcome before mRNA therapies can become truly widespread.
With these challenges in mind, Penn Engineering researchers are developing a new manufacturing technique that would be able to produce mRNA sequences on demand and on-site, isolating them in a way that removes the need for cryogenic temperatures. With more labs able to make and store mRNA-based therapeutics on their own, the “cold chain” between manufacturer and patient can be made shorter, faster and less expensive.
The National Science Foundation (NSF) is supporting this project, known as Distributed Ribonucleic Acid Manufacturing, or DReAM, through a four-year, $2 million grant from its Emerging Frontiers in Research and Innovation (EFRI) program.
The project will be led by Daeyeon Lee, Evan C Thompson Term Chair for Excellence in Teaching and Professor in the Department of Chemical and Biomolecular Engineering (CBE), along with Kathleen Stebe, Richer and Elizabeth Goodwin Professor in CBE and in the Department of Mechanical Engineering and Applied Mechanics. They will collaborate with Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, Drexel University’s Masoud Soroush and Michael Grady, the University of Oklahoma’s Dimitrios Papavassiliou and the University of Colorado Boulder’s Joel Kaar.
Read the full story in Penn Engineering Today.
Neurology, bioengineering, and physical medicine and rehabilitation might not seem like three disciplines that fit together, but for Flavia Vitale, an assistant professor of all three, it makes perfect sense. As the director and principal investigator at the Vitale Lab, her research focuses on developing new technologies that help to study how the brain and neuromuscular systems function.
Years ago, while she was working at Rice University developing new materials and devices that work in the body in a safer, more effective way, former president Barack Obama launched the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, aimed at revolutionizing the understanding of the human brain. This emphasis on how little is known about brain structure and function inspired Vitale to refocus her research on developing technology and materials that will help researchers solve the mysteries of the brain.
In 2018, she joined the faculty at the Perelman School of Medicine as an assistant professor of neurology, bioengineering, and physical medicine and rehabilitation, and founded the multidisciplinary Vitale Lab, where her team develops cutting edge materials and devices that will someday help clinicians diagnose and treat patients with complicated brain and neurological conditions. She is also one of the engineers looking forward to using new combined clinical/research facilities in neuroscience at Penn Medicine’s new Pavilion where new neurotechnoloigies will be developed and tested.
“My main goal is to create tools that can help solve mysteries of the brain, and address the needs of clinicians,” she says.
“My lab was recently awarded two grants totaling $4.5 million from the National Institute of Neurological Disorders and Stroke. In order to obtain more precise insights, noninvasively, into brain activity to improve gene therapy treatments for a range of diagnoses, from Parkinson’s disease to glioblastoma. The first grant is designated for the development of a novel surgical device for delivering gene-based therapeutics to the brain. The second is for optimization and pre-clinical validation of a novel EEG electrode technology, which uses a soft, flexible, conductive nanomaterial rather than metal and gels. We hope to confirm that these technologies work as well as, if not better than existing ones.”
Read the full story in Penn Medicine News.