Kevin Johnson Named AIMBE Fellow

Kevin B. Johnson, MD, MS

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.

Researchers Develop Technology to Keep Track of Living Cells and Tissues

SAFE Bioorthogonal Cycling

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, PhD

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, conducted postdoctoral research at Massachusetts General Hospital (MGH) and the Wyss Institute at Harvard University, and the work for this study was done under the supervision of 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, the 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 functions with 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.

Read the paper, “Spatiotemporal multiplexed immunofluorescence imaging of living cells and tissues with bioorthogonal cycling of fluorescent probes,” in Nature Biotechnology.

This study was supported by the Schmidt Science Fellows in Partnership with the Rhodes Trust and National Institutes of Health, National Cancer Institute (K99CA256353).

Bioengineering Graduate Student Hannah Zlotnick Named Schmidt Science Fellow

by Evan Lerner

Hannah Zlotnick

Hannah Zlotnick, a graduate student in the Department of Bioengineering and a member of the McKay Orthopaedic Research Laboratory in Penn’s Perelman School of Medicine, has been named a Schmidt Science Fellow.

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.

Read the full story in Penn Engineering Today.

How Bacteria Store Information to Kill Viruses (But Not Themselves)

by Luis Melecio-Zambrano

A group of bacteriophages, viruses that infect bacteria, imaged using transmission electron microscopy. New research sheds light on how bacteria fight off these invaders without triggering an autoimmune response. (Image: ZEISS Microscopy, CC BY-NC-ND 2.0)

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.

Read the full story in Penn Today.

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.

FDA Approves Penn Pioneered CAR T Cell Therapy for Third Indication

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 FDA approval 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.

Read the full announcement in Penn Medicine News.

Center for Engineering Mechanobiology 2.0: Developing ‘Mechanointelligence’

by Evan Lerner

The dynamics governing mechanointelligence vary greatly along time- and length-scales, so detailed models of individual cells and their components are necessary to connect the effects of their physical environments to the downstream effects those forces have on biological processes.

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.”

Read the full story in Penn Engineering Today.

Vivek Shenoy is Eduardo D. Glandt President’s Distinguished Professor in Materials Science and Engineering, Bioengineering and Mechanical Engineering and Applied Mechanics.

César de la Fuente Receives 2022 RSEQ Young Investigator Award

César de la Fuente, PhD

César de la Fuente, Presidential Assistant Professor in Psychiatry, Bioengineering, Microbiology, and in Chemical and Biomolecular Engineering has been honored with a 2022 Young Investigator Award by the Royal Spanish Society of Chemistry (RSEQ) for his pioneering research efforts to combine the power of machines and biology to help prevent, detect, and treat infectious diseases.

Read the RSEQ’s announcement here.

This story originally appeared in Penn Medicine News’s Awards & Accolades post for April 2022.

 

2022 Graduate Research Fellowships for Bioengineering Students

Congratulations to the two Bioengineering students to receive 2022 National Science Foundation Graduate Research Fellowship Program (NSF GRFP) fellowships. The prestigious NSF GRFP program recognizes and supports outstanding graduate students in NSF-supported fields. The eighteen Penn 2022 honorees were selected from a highly-competitive pool of over 12,000 applications nationwide. Further information about the program can be found on the NSF website.

 Gianna Therese Busch, PhD student, Bioengineering
Gianna is a member of the systems biology lab of Arjun Raj, Professor in Bioengineering and Genetics. Her research focuses on single-cell differences in cancer metabolism and drug resistance.

 

 

 

Shawn Kang, BSE/MSE, Bioengineering (’22)
Shawn conducted research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering, where he worked to develop more physiologically relevant models of human health and disease by combining organs-on-a-chip and organoid technology.

 

 

 

The following Bioengineering students also received Honorable Mentions:
Michael Steven DiStefano, PhD student
Rohan Dipak Patel, PhD student
Abraham Joseph Waldman, PhD student

Read the full list of NSF GRFP Honorees on the Grad Center at Penn website.

Penn Engineers Develop a New Method that Could Enable a Patient’s Own Antibodies to Eliminate Their Tumors

Tsourkas
Andrew Tsourkas, Ph.D.

One of the reasons that cancer is notoriously difficult to treat is that it can look very different for each patient. As a result, most targeted therapies only work for a fraction of cancer patients. In many cases, patients will have tumors with no known markers that can be targeted, creating an incredible challenge in identifying effective treatments. A new study seeks to address this problem with the development of a simple methodology to help differentiate tumors from healthy, normal tissues.

This new study, published in Science Advances, was led by Andrew Tsourkas, Professor in Bioengineering and Co-Director of the Center for Targeted Therapeutics and Translational Nanomedicine (CT3N), who had what he describes as a “crazy idea” to use a patient’s antibodies to find and treat their own tumors, taking advantage of the immune system’s innate ability to identify tumors as foreign. This study, spearheaded by Burcin Altun, a former postdoctoral researcher in Tsourkas’s lab, and continued and completed by Fabiana Zappala, a former graduate student in Penn Bioengineering, details their new method for site-specifically labeling “off-the-shelf” and native serum autoantibodies with T cell–redirecting domains.

Researchers have known for some time that cancer patients will generate an antibody response to their own tumors. These anti-tumor antibodies are quite sophisticated in their ability to specifically identify cancer cells; however, they are not sufficiently potent to confer a therapeutic effect. In this study, Tsourkas’s team converted these antibodies into bispecific antibodies, thereby increasing their potency. T cell-redirecting bispecific antibodies are a new form of targeted therapeutic that forms a bridge between tumor cells and T cells which have been found to be as much as a thousand-times more potent than antibodies alone. By combining the specificity of a patient’s own antibodies with the potency of bispecific antibodies, researchers can effectively create a truly personalized therapeutic that is effective against tumors.

In order to test out this new targeted therapeutic approach, the Tsourkas lab had to develop an entirely new technology, allowing them to precisely label antibodies with T cell targeting domains, creating a highly homogeneous product.  Previously it has not been possible to convert native antibodies into bispecific antibodies, but Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine or TITAN lab specializes in the creation of novel targeted imaging and therapeutic agents for detection and treatment of various diseases. “Much is yet to be done before this could be considered a practical clinical approach,” says Tsourkas. “But I hope at the very least this works stimulates new ideas in the way we think about personalized medicine.”

In their next phase, Tsourkas’s team will be working to separate anti-tumor antibodies from other antibodies found in patients’ serum (which could potentially redirect the bispecific antibodies to other locations in the body), as well as examining possible adverse reactions or unintended effects and immunogenicity caused by the treatment. However, this study is just the beginning of a promising new targeted therapeutic approach to cancer treatment.

This work was supported by Emerson Collective and the National Institutes of Health, National Cancer Institute (R01 CA241661).

Exploring the History of CAR-T Cell Therapy

Carl June, MD

A new feature in Chemistry World explores the history of CAR (chimeric antigen receptor)-T cell therapy, a revolutionary type of therapeutic treatment for certain types of cancer. One of the pioneers of CAR-T cell therapy is Carl June, Richard W. Vague Professor in Immunotherapy in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group. His groundbreaking research opened the door for FDA approval of the CAR T therapy called Kymriah, which treats acute lymphoblastic leukemia (ALL), one of the most common childhood cancers.

Read “A decade of CAR-T cell therapy” in Chemistry World.