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, 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.
This study was supported by the Schmidt Science Fellows in Partnership with the Rhodes Trust and National Institutes of Health, National Cancer Institute (K99CA256353).
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.
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.
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 2022 cohort of PEP, PIP, and PSP winners smile for a photo with Interim President Wendell Pritchett and Interim Provost Beth Winkelstein.
Last week, on a sunny spring day, the 2022 President’s Engagement, Innovation, and Sustainability Prize winners were recognized at a special luncheon, a momentous occasion that hasn’t taken place in-person since 2019. The 12 Prize recipients and their advisers, as well as past Prize winners and Penn leadership, joined together at the University Meeting and Guest House for a meal, good conversation, and celebration.
To the group, as well as family members tuning in through Zoom, Interim President Wendell Pritchett described this year’s winners as exemplifying creativity and leadership. “They epitomize why these prizes are central to the vision we share for Penn,” he said, before distributing handcrafted certificates to each of the six teams.
Eli Moraru, who earned one of the inaugural President’s Sustainability Prizes for his nonprofit The Community Grocer, said the event was uplifting for two main reasons: The first being that he got to network with his fellow PEP/PIP/PSP cohort, and the second being his connection with past Prize winners.
“It’s a real community,” Moraru said, sharing, as an example, how Christina Miranda from Be Body Positive Philly—a winner in the 2021 cohort—approached him expressing her interest in serving as a resource to his team in any way possible.
“It’s just one more reason showcasing how we aren’t alone in this,” Moraru said.
Chosen from an applicant pool of 71 people, the two other President’s Sustainability Prize-winning teams include Saif Khawaja for Shinkei Systems and Sarah Beth Gleeson, Shoshana Weintraub, and Julia Yan for EcoSPIN. Earning a President’s Innovation Prize, which was founded in 2016, is William Kohler Danon and Lukas Achilles Yancopoulos for Grapevine. In 2015, the very first President’s Engagement Prizes were announced. This year, Penn awarded this honor to two teams: Seungkwon Son, Max Strickberger, and Sam Strickberger for College Green Ventures and Manoj Simha and Rowana Miller from Cosmic Writers. Each team receives $100,000 to help get their projects off the ground, plus a $50,000 living stipend post-graduation per person.
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.”
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, 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.
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
William Danon and Luka Yancopoulos, winners of the 2022 President’s Innovation Prize, will offer a software solution to make the health care supply chain more efficient.
by Brandon Baker
William Danon and Luka Yancopoulos pose in front of College Hall in April 2022. They are co-founders of Grapevine and the winners of the 2022 President’s Innovation Prize.
William Danon and Luka Yancopoulos are best friends. They’re also business partners.
The duo, who received this year’s President’s Innovation Prize (PIP) for Grapevine, met during sophomore year, connected through Yancopoulos’ roommate. As time went on, they did everything together: cooked meals, played basketball, and read and discussed fantasy novels.
“We spent a lot of time together,” Danon says.
It was only natural, then, that when the time came to start an actual venture, they’d do it together.
“They’re like brothers, in a very good way,” says mentor David Meaney of the School of Engineering and Applied Science, who describes their working dynamic as “complementary.” “I think that will serve them well. Most of what we do in faculty is collaborative, and I see elements of that in their partnership. I give them credit for stepping out and doing something unusual and keeping at it.”
How Grapevine came to be
Grapevine is a software solution and professional networking platform that connects small-to-medium-size players in the health care supply chain. It’s a sort of two-pronged solution: It helps institutions like hospital systems connect disjointed operations like procurement and inventory management internally, but also serves as a glue between these institutions and purveyors of medical equipment.
“William and Luka are impact-driven entrepreneurs whose collaborative synergies will take them far,” says Penn Interim President Wendell Pritchett. “The software provided by Grapevine is poised to reinvent how the health care industry buys and sells medical supplies and services and, truly, could not come at a timelier moment.”
The company is the evolution of a project they began at the onset of the COVID-19 pandemic, called Pandemic Relief Supply, which delivered $20 million of health care supplies to frontline workers.
“My mom was a nurse practitioner at New York Presbyterian Hospital, the largest hospital in the United States, and she was coming home with horror stories,” recalls Yancopoulos. “In surgery or the ER, a surgeon had to put on a garbage bag because they didn’t have a gown. And they gave her one mask to use for the rest of the month, and I’m seeing on the news, ‘Don’t wear a mask for more than three days.’”
This is where Yancopoulos and Danon first developed an interest in the health care supply chain. Using a database Penn allows students access to that maps the import of any good in the country, they did keyword matching to identify instreams of different goods and handed off findings to New York Presbyterian procurement staff. When McKesson, the largest provider of health care products and services in the U.S., took notice of what they were doing and reached out, they realized they were onto something. In response to their success, they started a company called Pandemic Relief Supply to distribute reliable medical supplies, including items like medical-grade masks and gloves, to frontline workers in the healthcare space.
As time passed, that project evolved into something larger: Grapevine.
A mock-up screenshot of a business profile on the Grapevine professional networking platform. (Image: William Danon)
In short, Grapevine’s software creates a professional networking platform to resolve miscommunications between suppliers and buyers, as well as adds a layer of transparency between interactants. Suppliers on the platform display real-time data about their inventory and shipping process, with timestamps; this prohibits companies from cherry-picking data or making false claims and creates a more health-care-supply-specific space for companies to interact than, say, LinkedIn.
“Primarily, the first step is we want people to use it internally, and streamline operations, and then through that centralized operational data, you can push that externally and that’s where [Grapevine] becomes a connector,” explains Danon. “Because when you’re choosing to connect with someone, the reason you can do so way more efficiently or quickly, is that data is actual operational data.”
To accomplish this level of transparency, the beginnings of Grapevine involved lots of legwork. Last year, the duo moved to Los Angeles to take stock of what suppliers existed where, and how reliable they were. They realized that many suppliers existed around Los Angeles because of port access; many medical supplies are imported from Asia. Their time in LA made the problem feel even more tangible, they agree.
“We were able to see people were doing outdated processes—manual processes—because there’s no other option,” Danon says. “So, we said, ‘Let’s get out there and do some work to be digital and technologically innovative.”
N.B.: Yancopolous’s senior design team created “Harvest” for their capstone project in Bioengineering, building on the existing Grapevine software package. Read Harvest’s abstract and view their final presentation on the BE Labs website.
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 inScience 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).
Shawn Kang, BSE/MSE, Bioengineering (’22)
