A Philadelphia life sciences company spun out of Penn is emerging from stealth mode with nearly $10 million from a seed funding round. Vittoria Biotherapeutics’ mission is to overcome limitations of CAR T cell therapy by using unique cell engineering and gene editing technologies to create new therapies that address unmet clinical needs. The technology the company is attempting to commercialize was developed by Marco Ruella, M.D., Assistant Professor of Medicine in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group, who is the company’s scientific founder.
Carl June, MD, Professor in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group, was quoted in a recent press release announcing a new international partnership between Penn Medicine (PSOM), the Children’s Hospital of Pennsylvania (CHOP), and Costa Rica’s CCSS, or the Caja Costarricense de Seguro Social (Social Security Program), to develop CAR T research in Costa Rica. June is a world renowned cancer cell therapy pioneer whose research led to the initial development and FDA approval of CAR T cell therapy:
“‘At least 15,000 patients across the world have received CAR T cells, and dozens more clinical trials using this approach are in progress, for almost every major tumor type, but people in many parts of the globe still do not have access to treatment with these transformative therapies,’ said Carl H. June, MD, the Richard W. Vague Professor in Immunotherapy and director of the Center for Cellular Immunotherapies in Penn’s Perelman School of Medicine. “We are honored to work with our colleagues in Costa Rica in hopes of building a path for patients in underserved areas to have the opportunity to benefit from clinical research programs offering this personalized therapy.’”
César de la Fuente, Presidential Assistant Professor in Bioengineering, Microbiology, Psychiatry, and Chemical and Biomolecular Engineering, co-led a team of researchers who created autonomous particles covered with patches of protein “motors,” with the goal that these bots can eventually carry livesaving drugs through bodily fluids.
Yale E. Cohen, Professor of Otorhinolaryngology, with secondary appointments in Neurscience and Bioengineering, was appointed Assistant Dean of Research Facilities and Resources at the Perelman School of Medicine at the University of Pennsylvania, effective April 1, 2022. Cohen is currently Chair of the Penn Bioengineering Graduate Group, and Director of the Hearing Sciences Center:
“Many of you are already quite familiar with Dr. Cohen, as his leadership roles in research training and education at PSOM and the University are far-reaching and impactful. Dr. Cohen is a Professor of Otorhinolaryngology with secondary appointments in the Department of Neuroscience and Engineering’s Department of Bioengineering. Recognized widely for his deep commitment to our teaching and training community, Dr. Cohen chairs the Bioengineering Graduate Group, and in 2020 received the prestigious Jane M. Glick Graduate Student Teaching Award, which honors clinicians and scientists who exemplify outstanding quality of patient care, mentoring, research, and teaching.”
Kevin B. Johnson, David L. Cohen University Professor in Biostatistics, Epidemiology and Informatics and in Computer and Information Science, has been elected to the 2022 Class of the American Institute for Medical and Biological Engineering (AIMBE) Fellows. Johnson joined the Penn faculty in 2021. He also holds secondary appointments in Bioengineering, in Pediatrics, and in the Annenberg School for Communication, and is the Vice President for Applied Informatics for the University of Pennsylvania Health System.
Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer. 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.”
Johnson was nominated, reviewed, and elected by peers and members of the AIMBE College of Fellows for his pioneering discoveries in clinical informatics, leading to advances in data acquisition, medication management, and information aggregation in medical settings.
A formal induction ceremony was held during AIMBE’s 2022 Annual Event on March 25, 2022. Johnson was inducted along with 152 colleagues who make up the AIMBE Fellow Class of 2022. For more information about the AIMBE Annual Event, please visit www.aimbe.org.
Read Johnson’s AIMBE election press release here. Find the full list of 2022 Fellows here.
Cells in complex organisms undergo frequent changes, and researchers have struggled to monitor these changes and create a comprehensive profile for living cells and tissues. Historically researchers have been limited to only 3-5 markers due to spectral overlaps in fluorescence microscopy, an essential tool required for imaging cells. With only this small handful of markers, it is difficult to monitor protein expressions of live cells and a comprehensive profile of cellular dynamics cannot be created. However, a new study in Nature Biotechnology addresses these limitations by demonstrating a new method for comprehensive profiling of living cells.
Jina Ko, Assistant Professor in Bioengineering in the School of Engineering and Applied Science and in Pathology and Laboratory Medicine in the Perelman School of Medicine, served as lead author of this new study. Ko conducted postdoctoral research at Massachusetts General Hospital (MGH) and the Wyss Institute at Harvard University, and the work for this study was done in collaboration with Jonathan Carlson M.D., Ph.D. and Ralph Weissleder M.D., Ph.D. of MGH. Ko’s lab at Penn develops novel technologies using bioengineering, molecular biology, and chemistry to address diagnostic challenges for precision medicine.
To address these limitations in microscopy, Ko’s team developed a new chemistry tool which was highly gentle to cells. This “scission-accelerated fluorophore exchange (or SAFE)” method utilizes “click” chemistry, a type of chemistry that follows examples found in nature to create fast and simple reactions. This new SAFE method enabled Ko to achieve non-toxic conditions to living cells and tissues, whereas previous methods have used harsh chemicals that would strip off fluorophores and consequently would not work with living cells and tissues.
With the development of SAFE, the authors demonstrated that researchers can now effectively perform multiple cycles of cell profiling and can monitor cellular changes over the course of their observations. Instead of the previous limitation of 3-5 markers total, SAFE allows for many more cycles and can keep track of almost as many markers as the researcher wants. One can now stain cells and quench/release fluorophores and repeat the cycle multiple times for multiplexing on living cells. Each cycle can profile 3 markers, and so someone interested in profiling 15 markers could easily perform 5 cycles to achieve this much more comprehensive cell profile. With this breakthrough in more detailed imaging of cells, SAFE demonstrates broad applicability for allowing researchers to better investigate the physiologic dynamics in living systems.
She joins 28 early-career scientists from around the world in this year’s cohort, with each receiving support for one to two years, $100,000 in salary support per year, individualized mentoring, and a series of professional development sessions as they pivot to the next stages of their research agendas.
The fellowship is a program of Schmidt Futures, the philanthropic initiative of Eric and Wendy Schmidt that aims to tackle society’s toughest challenges by supporting interdisciplinary researchers at the start of their careers.
“Our latest group of Schmidt Science Fellows embodies our vision for this Program at its inception five years ago,” says Eric Schmidt, co-founder of Schmidt Futures and former CEO and Chairman of Google. “We find the most talented next-generation leaders from around the world and back these impressive young adults with the resources and networks they need to realize their full potential while addressing some of the big scientific questions facing the world. Congratulations to the 2022 Schmidt Science Fellows, I am excited to see where your science takes you and what you will achieve.”
Working at the intersection of materials science, biology, and applied clinical research, Zlotnick’s postdoctoral work will involve developing advanced bioprinting techniques for regenerative medicine. Such advances are necessary to recreate the multi-cellular composition of orthopedic tissues, such as those found in the knee joint. Lab-grown tissue models can then be used to broaden our understanding of how degenerative diseases progress after injury, limit the need for animal models, and serve as a platform for therapeutic discovery.
During the last few years, CRISPR has grabbed headlines for helping treat patients with conditions as varied as blindness and sickle cell disease. However, long before humans co-opted CRISPR to fight genetic disorders, bacteria were using CRISPR as an immune system to fight off viruses.
In bacteria, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) works by stealing small pieces of DNA from infecting viruses and storing those chunks in the genes of the bacteria. These chunks of DNA, called spacers, are then copied to form little tags, which attach to proteins that float around until they find a matching piece of DNA. When they find a match, they recognize it as a virus and cut it up.
Now, a paper published in Current Biology by researchers from the University of Pennsylvania Department of Physics and Astronomy shows that the risk of autoimmunity plays a key role in shaping how CRISPR stores viral information, guiding how many spacers bacteria keep in their genes, and how long those spacers are.
Ideally, spacers should only match DNA belonging to the virus, but there is a small statistical chance that the spacer matches another chunk of DNA in the bacteria itself. That could spell death from an autoimmune response.
“The adaptive immune system in vertebrates can produce autoimmune disorders. They’re very serious and dangerous, but people hadn’t really considered that carefully for bacteria,” says Vijay Balasubramanian, principal investigator for the paper and the Cathy and Marc Lasry Professor of Physics in the School of Arts & Sciences.
Balancing this risk can put the bacteria in something of an evolutionary bind. Having more spacers means they can store more information and fend off more types of viruses, but it also increases the likelihood that one of the spacers might match the DNA in the bacteria and trigger an autoimmune response.
Vijay Balasubramanian is the Cathy and Marc Lasry Professor of Physics at the Department of Physics and Astronomy of the University of Pennsylvania, a visiting professor at Vrije Universiteit Brussel, and a member of the Penn Bioengineering Graduate Group.
The U.S. Food and Drug Administration has expanded its approval for Kymriah, a personalized cellular therapy developed at the Abramson Cancer Center, this time for the treatment of adults with relapsed/refractory follicular lymphoma who have received at least two lines of systemic therapy. “Patients with follicular lymphoma who relapse or don’t respond to treatment have a poor prognosis and may face a series of treatment options without a meaningful, lasting response,” said Stephen J. Schuster, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma in the Division of Hematology Oncology. It’s the third FDAapproval for the “living drug,” which was the first of its kind to be approved, in 2017, and remains the only CAR T cell therapy approved for both adult and pediatric patients.
“In just over a decade, we have moved from treating the very first patients with CAR T cell therapy and seeing them live healthy lives beyond cancer to having three FDA-approved uses of these living drugs which have helped thousands of patients across the globe,” said Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center and director of the Parker Institute for Cancer Immunotherapy at Penn. “Today’s news is new fuel for our work to define the future of cell therapy and set new standards in harnessing the immune system to treat cancer.”
Research from June, a member of the Penn Bioengineering Graduate Group, led to the initial 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.
The National Science Foundation’s Science and Technology Center (STC) program is its flagship funding mechanism for organizing interdisciplinary research on cutting-edge topics. Penn’s Center for Engineering MechanoBiology (CEMB) is one of the 18 active STCs, bringing together dozens of researchers from Penn Engineering and the Perelman School of Medicine, as well as others spread across campus and at partner institutions around the world.
With its NSF funding now renewed for another five years, the Center is entering into a new phase of its mission, centered on the nascent concept of “mechanointelligence.”
Mechanobiology is the study of the physical forces that govern the behavior of cells and their communication with their neighbors. Mechanointelligence adds another layer of complexity, attempting to understand the forces that allow cells to sense, remember and adapt to their environments.
Ultimately, harnessing these forces would allow researchers to help multicellular organisms — plants, animals and humans — better adapt to their environments as well.
“Mechanointelligence is a key element of a cell’s ability to survive and reproduce,” says CEMB Director and Eduardo D. Glandt President’s Distinguished Professor Vivek Shenoy. “Just like with complex organisms, a cell’s ‘fitness’ depends on its environment, and adapting means rewiring how its genes are expressed.”