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).
In a course from Annenberg’s David Lydon-Staley, seven graduate students conducted single-participant experiments. This approach, what’s known as an “n of 1,” may better capture the nuances of a diverse population than randomized control trials can.
David Lydon-Staley is an assistant professor of communication and principal investigator of the Addiction, Health, & Adolescence Lab in the Annenberg School for Communication.
To prep for an upcoming course he was teaching, Penn researcher David Lydon-Staley decided to conduct an experiment: Might melatonin gummies—supplements touted to improve sleep—help him, as an individual, fall asleep faster?
For two weeks, he took two gummies on intervention nights and none on control nights. The point, however, wasn’t really to find out whether the gummies worked for him (which they didn’t), but rather to see how an experiment with a single participant played out, what’s known as an “n of 1.”
Randomized control experiments typically include hundreds or thousands of participants. Their aim is to show, on average, how the intervention being studied affects people in the treatment group. But often “there’s a failure to include women and members of minoritized racial and ethnic groups in those clinical trials,” says Lydon-Staley, an assistant professor in the Annenberg School for Communication. “The single-case approach says, instead of randomizing a lot of people, we’re going to take one person at a time and measure them intensively.”
In Lydon-Staley’s spring semester class, Diversity and the End of Average, seven graduate students conducted their own n-of-1 experiments—on themselves—testing whether dynamic stretching might improve basketball performance or whether yoga might decrease stress. One wanted to understand the effect of journaling on emotional clarity. They also learned about representation in science, plus which analytical approaches might best capture the nuance of a diverse population and individuals with many intersecting identities.
“It’s not just an ‘n of 1’ trying to do what the big studies are doing. It’s a different perspective,” says Lydon-Staley. “Though it’s just one person, you’re getting a much more thorough characterization of how they’re changing from moment to moment.”
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.
Cathy and Marc Lasry Professor Vijay Balasubramanian at Penn’s BioPond.
In an interview with Quanta Magazine, Vijay Balasubramanian discusses his work as a theoretical physicist, noting his study of the foundations of physics and the fundamentals of space and time. He speaks of the importance of interdisciplinary study and about how literature and the humanities can contextualize scientific exploration in the study of physics, computer science, and neuroscience.
Balasubramanian is Cathy and Marc Lasry Professor in the Department of Physics and Astronomy in the Penn School of Arts and Sciences and a member of the Penn Bioengineering Graduate Group.
Congratulations to recent Penn Bioengineering graduate Jason Andrechak on winning a Graduate Leadership Awards for 2022. Each year a select number of students across the university are recognized for their service and lasting contributions to graduate student life at Penn. Andrechak, one of only ten recipients in 2022, won a Dr. Andy Binns Award for Outstanding Service to Graduate and Professional Student Life. This award is presented to “graduate or professional students, upon their graduation from Penn, who have significantly impacted graduate and professional student life through service involvement in student life initiatives or organizations.” Andrechak won this award for his “service and leadership in advocating for equity and accessibility during the transition to virtual operations and following a period of leadership transition within the Graduate and Professional Student Assembly (GAPSA). ”
Andrechak completed his Ph.D. in Bioengineering in 2022, where he studied macrophage immunotherapy in solid tumors in the lab of Dennis E. Discher, Robert D. Bent Professor in Chemical and Biomolecular Engineering, Bioengineering, and Mechanical Engineering and Applied Mechanics. He was named a National Science Foundation Graduate Research Fellow in 2018. He has actively led the Graduate Association of Bioengineers (GABE) as Community Service & Outreach chair from 2017-2019 and as co-President from 2019-2022. He also served as the Director of Equity & Access for the Graduate & Professional Student Assembly (GAPSA) from 2020-2021, in addition to several other service and advisory roles at the department, school, and university levels.
Learn more about the Penn Graduate Leadership Awards and read the full list of recipients on the Grad Center at Penn website.
Each year, Penn Engineering’s seniors present their Senior Design projects, a year-long effort that challenges them to test and develop solutions to real-world problems, to their individual departments. The top three projects from each department go on to compete in the annual Senior Design Competition, sponsored by the Engineering Alumni Society, which involves pitching projects to a panel of judges who evaluate their potential in the market.
This year’s panel included 42 judges, 21 in-person and 21 online, who weighed in on 18 projects. Each winning team received a $2,000 prize, generously sponsored by Penn Engineering alumnus Kerry Wisnosky.
This year, Bioengineering teams won two of the four interdepartmental awards.
Technology & Innovation Award
This award recognized the team whose project represents the highest and best use of technology and innovation to leverage engineering principles.
Team Modulo Prosthetics with Vijay Kumar, Dean of Penn Engineering, and Lyle Brunhofer, Chair of the 2022 Senior Design Competition Committee.
Winner: Team Modulo Prosthetics Department: Bioengineering Team Members: Alisha Agarwal, Michelle Kwon, Gary Lin, Ian Ong, Zachary Spalding Mentor: Michael Hast Instructors: Sevile Mannickarottu, David Meaney, Michael Siedlik Abstract: Modulo Prosthetic is an adjustable, low-cost, thumb prosthetic with integrated haptic feedback that attaches to the metacarpophalangeal (MCP) joint of partial hand amputees and assists in activities of daily living (ADLs).
Leadership Award
This award recognizes the team which most professionally and persuasively presents their group project to incorporate a full analysis of their project’s scope, advantages and challenges, as well as addresses the research’s future potential and prospects for commercialization.
Team ReiniSpec with Vijay Kumar, Dean of Penn Engineering, and Lyle Brunhofer, Chair of the 2022 Senior Design Competition Committee.
Winner: Team ReiniSpec Department: Bioengineering Team Members: Caitlin Frazee, Caroline Kavanagh, Ifeoluwa Popoola, Alexa Rybicki, Michelle White Mentor: JeongInn Park Instructors: Sevile Mannickarottu, David Meaney, Michael Siedlik Abstract: ReiniSpec is a redesigned speculum to improve the gynecological exam experience, increasing patient comfort with a silicone shell and using motorized arm adjustments to make it easily adjustable for each patient, while also incorporating a camera, lights, and machine learning to aid in better diagnosis by gynecologists.
The 2022 Senior Design Competition Committee was chaired by Lyle Brunhofer, Penn Engineering Alumni Society Board Member and alumnus of Penn Bioengineering (BSE 2014, Master’s 2015).
Shawn Kang, BSE/MSE, Bioengineering (’22)
