In a recent CNN feature, César de la Fuente, Presidential Assistant Professor in Bioengineering, Psychiatry, Microbiology, and in Chemical and Biomolecular Engineering commented on a study about a new type of antibiotic that was discovered with artificial intelligence:
“I think AI, as we’ve seen, can be applied successfully in many domains, and I think drug discovery is sort of the next frontier.”
The de la Fuente lab uses machine learning and biology to help prevent, detect, and treat infectious diseases, and is pioneering the research and discovery of new antibiotics.
“Macrophages killing cancer cell” photographed by Susan Arnold.
By silencing the molecular pathway that prevents macrophages from attacking our own cells, Penn Engineers have manipulated these white blood cells to eliminate solid tumors.
Cancer remains one of the leading causes of death in the U.S. at over 600,000 deaths per year. Cancers that form solid tumors such as in the breast, brain or skin are particularly hard to treat. Surgery is typically the first line of defense for patients fighting solid tumors. But surgery may not remove all cancerous cells, and leftover cells can mutate and spread throughout the body. A more targeted and wholistic treatment could replace the blunt approach of surgery with one that eliminates cancer from the inside using our own cells.
Dennis Discher, Robert D. Bent Professor in Chemical and Biomolecular Engineering, Bioengineering, and Mechanical Engineering and Applied Mechanics, and postdoctoral fellow, Larry Dooling, provide a new approach in targeted therapies for solid tumor cancers in their study, published in Nature Biomedical Engineering. Their therapy not only eliminates cancerous cells, but teaches the immune system to recognize and kill them in the future.
“Due to a solid tumor’s physical properties, it is challenging to design molecules that can enter these masses,” says Discher. “Instead of creating a new molecule to do the job, we propose using cells that ‘eat’ invaders – macrophages.”
Macrophages, a type of white blood cell, immediately engulf and destroy – phagocytize – invaders such as bacteria, viruses, and even implants to remove them from the body. A macrophage’s innate immune response teaches our bodies to remember and attack invading cells in the future. This learned immunity is essential to creating a kind of cancer vaccine.
But, a macrophage can’t attack what it can’t see.
“Macrophages recognize cancer cells as part of the body, not invaders,” says Dooling. “To allow these white blood cells to see and attack cancer cells, we had to investigate the molecular pathway that controls cell-to-cell communication. Turning off this pathway – a checkpoint interaction between a protein called SIRPa on the macrophage and the CD47 protein found on all ‘self’ cells – was the key to creating this therapy.”
Multiple members in the biophysical engineering lab lead by Dennis Discher, including co-lead author and postdoctoral fellow and Penn Bioengineering alumnus Jason Andrechak and Bioengineering Ph.D. student Brandon Hayes, contributed to this study. The research was funded by grants from the National Heart, Lung, and Blood Institute and the National Cancer Institute, including the Physical Sciences Oncology Network, of the US National Institutes of Health.
Daeyeon Lee, Professor and Evan C Thompson Term Chair for Excellence in Teaching in the Department of Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group, is the recipient of two recent honors.
Daeyeon Lee of the School of Engineering and Applied Science delivers the 2023 Thompson Chair Lecture on April 4, 2023. He spoke about reconnecting in the classroom and building community.
“Students who feel connected with instructors and among peers will invest more time, work harder, and retain information better, because they feel comfortable and safe being in the classroom and making space,” Lee said in his opening remarks. “So, there are clearly lots of positive benefits to having this connectedness among students in the classroom.”
Lee’s lecture, titled “(Re)connecting in the Classroom,” was inspired by the “Great Disengagement” referenced in an article published in The Chronicle of Higher Education last year. It portrayed students as more disconnected and uncertain as they re-entered the campus environment.
Read more about Lee’s “(Re)connecting in the Classroom” in Penn Today.
In addition, Lee has received the 2022 Outstanding Achievement Award in Nanoscience from the American Chemical Society (ACS).
The annual award recognizes exceptional achievements in nanoscience research and notable leadership in the area of colloidal nanoparticles and application. Lee was chosen from a large group of extraordinary nominees among the invited speakers, “for pioneering research in development of factory-on-a-chip and its application for large scale nanoparticle synthesis and functionalization.”
Front, from left to right: Lucy Andersen, Vice Provost for Education Karen Detlefsen, Derek Yang, Ann Ho, and Arianna James. Back, from left to right: Ritesh Isuri, Adiwid (Boom) Devahastin Na Ayudhya, Oualid Merzouga, and Puneeth Guruprasad.
Ten winners of the 2023 Penn Prize for Excellence in Teaching by Graduate Students were announced at a ceremony held April 13 at the Graduate Student Center. The recipients, who represented five of Penn’s 12 schools, were recognized among a pool of 44 Ph.D. candidates and master’s students nominated primarily by undergraduates—a quality unique to and cherished about this Prize.
“It’s a particularly authentic expression of gratitude from undergraduates, and that’s really the pleasure [of presenting these awards],” says Vice Provost for Education Karen Detlefsen, who was present to announce the winners and award them with a certificate. (They also receive a monetary award.) “I’m so proud of our students: Our undergraduates, for taking the time to recognize what it is our graduate students contribute to the student body, and the graduate students who are contributing to the life of the University.
“Students are the lifeblood of the University and without them, we wouldn’t be here.”
The Prize began in the 1999-2000 academic year under former Penn President Judith Rodin. It was spearheaded by then-doctoral-candidate Eric Eisenstein and has been issued every year since. Nominations for the Prize often mention how graduate teaching assistants were able to take a complex subject and make it relatable or craft a course like philosophy or mathematics into an enjoyable—even highly anticipated—experience for students.
“Many nominations show how much students value a TA or a graduate instructor of record who shows that they care for their learning and for them as people, and who makes themself readily available to assist,” says Ian Petrie, director of graduate student programming for the Center for Teaching and Learning, who organizes the selection committee for the Prize. “Typically, however, committee members are also interested in seeing nominations that really point to how a graduate student instructor taught or gave feedback—not just how responsive they were to emails or how many office hours they had.”
He also emphasizes that many winners this year were not just teachers, but mentors—often helping undergraduates or new graduate students navigate not only the course but also Penn as an institution.
Puneeth Guruprasad
One of the winners, Puneeth Guruprasad, hails from Penn Bioengineering. Guruprasad is a fourth-year Ph.D. student in Bioengineering who conducts research in the lab of Marco Ruella, Assistant Professor of Medicine in the Division of Hematology/Oncology in the Perelman School of Medicine. Ruella is also a member of the Center for Cellular Immunotherapies (CCI) and the Penn Bioengineering Graduate Group.
Guruprasad studies mechanisms of resistance to chimeric antigen receptor (CAR) T cell therapy for cancer. He has served as a teaching assistant for five semesters: three for Intro to Biotransport Processes (BE 3500) taught by Alex Hughes, Assistant Professor in Bioengineering, and two for Cellular Engineering (BE 3060), taught by Daniel Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and in Chemical and Biomolecular Engineering. Both courses are a part of the core curriculum for undergraduate bioengineering students. His doctoral thesis focuses on how a specific interaction between CAR T cells and tumor cells limits their function across a range of cancers.
“I make myself approachable outside the classroom, and I think that’s one aspect of being a TA: having responsibilities that extend beyond the classroom,” says Guruprasad. “Dozens of times, I’ve spoken to students over coffee, or over some lunch, about what direction they want to take in their life, what they want to do outside of the course, and give them my two cents of advice. I try to individualize.”
This post was adapted from an original story by Brandon Baker in Penn Today. Read the full story and list of 2023 winners here.
Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer, with AIMBE Fellows representing the top 2% of medical and biological engineers. 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.”
Nominated and reviewed by peers and members of the College of Fellows, de la Fuente was elected Fellow “for the development of novel antimicrobial peptides designed using principles from computation, engineering and biology.”
A formal ceremony will be held during the AIMBE Annual Event in Arlington, Virginia on March 27, 2023, where de la Fuente will be inducted along with 140 colleagues who make up the AIMBE College of Fellows Class of 2023.
AIMBE Fellows are among the most distinguished medical and biological engineers, including 3 Nobel Prize laureates and 17 Fellows having received the Presidential Medal of Science and/or Technology and Innovation, along with 205 having been inducted into the National Academy of Engineering, 105 into the National Academy of Medicine and 43 into the National Academy of
Sciences.
Dahin Song, a third year undergraduate student in Bioengineering, penned a guest blog post for Penn Career Services as part of their ongoing series of posts by recipients of the 2022 Career Services Summer Funding Grant. In this post, Song talks about her opportunity to conduct research in the SMART Lab of Daeyeon Lee, Professor and Evan C. Thompson Term Chair for Excellence in Teaching in the Department of Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group. During her summer research, Song worked on increasing the stability of the monolayer in microbubbles, gas particles which have been put to therapeutic use. She writes:
“My project was on increasing the stability of the monolayer using cholesterol; theoretically, this would decrease the permeability while maintaining the fluidity of the monolayer. Being given my own project at the get-go was initially intimidating; initial learning curve was overwhelming – along with new wet lab techniques and protocols, I learned a whole new topic well enough to ask meaningful questions. But in retrospect, throwing myself headlong into a project was the best method to immerse me in the research environment, especially as a first-time researcher. I learned how to read papers efficiently, troubleshoot research problems, navigate in a laboratory environment, and be comfortable with working independently but more importantly, with others.”
Interim Provost Beth A. Winkelstein has announced the appointment of Russell J. Composto as Faculty Co-Director of Penn First Plus (P1P), beginning July 1, 2023. Composto is currently Professor of Materials Science and Engineering with secondary appointments in Bioengineering and Chemical and Biomolecular Engineering, Howell Family Faculty Fellow, and Associate Dean for Undergraduate Education in Penn Engineering.
“Russ Composto has long been one of our campus leaders in advancing support and mentoring for our students,” said Interim Provost Winkelstein, “including new programs for student wellness, community service, and research and mentoring for first-generation and/or low-income students. He is one of the leaders of our exciting new initiative to increase inclusivity in STEM education at Penn, which just received a major six-year grant from the Inclusive Excellence initiative of the Howard Hughes Medical Institute. Within Penn Engineering, he led the development of a new engineering curriculum and a new program of individualized student advising, both of which have been highly successful in enhancing the academic experiences of our undergraduates.
“I am extremely grateful to Robert Ghrist for his longstanding dedication to Penn’s undergraduates and his leadership over the past five years as an inaugural Faculty Co-Director of P1P, as well as to ongoing Faculty Co-Director Camille Charles, Executive Director Marc Lo, and the outstanding P1P staff and extended team for their work in sustaining P1P’s invaluable mission on our campus.”
Penn First Plus, founded in 2018, provides support, resources and community-building for undergraduate students who identify as lower- to middle-income and/or are the first in their families to attend college. It includes the Shleifer Family Penn First Plus Center in College Hall and the Pre-First Year Program, an intensive four-week summer program for select incoming first-year students, preceding New Student Orientation, that offers comprehensive support services which continue throughout students’ undergraduate experiences at Penn.
Composto has served as Associate Dean for Undergraduate Education in Penn Engineering since 2015. In more than thirty years at Penn, he has also served as both Undergraduate Chair and Graduate Group Chair of Materials Science and Engineering and has been awarded the Provost’s Award for Distinguished Ph.D. Teaching and Mentoring, the Geoffrey Marshall Mentoring Award of the Northeastern Association of Graduate Schools, and the Ford Motor Company Award for Faculty Advising.
He is a world-leading pioneer of polymer science who is a Fellow and former Chair of the Division of Polymer Physics of the American Physical Society, has received a Special Creativity Award from the National Science Foundation, and recently became Co-Director of a major NSF-funded initiative to bring together soft matter, data science, and science policy as part of the NSF Research Traineeship Program, which encourages transformative models for training of STEM graduate students, especially in new, high-priority interdisciplinary research areas. He received a Ph.D. and M.S. from Cornell University and a B.A. in Physics from Gettysburg College.
A team of researchers led by the School of Arts & Science’s Wei Guo offers new insights into a mechanism that promotes tumor growth. “This information could be used to help clinicians diagnose cancers earlier in the future,” says Guo.
In many instances, the physical manifestation of cancers and the ways they are subsequently diagnosed is via a tumor, tissue masses of mutated cells and structures that grow excessively. One of the major mysteries in understanding what goes awry in cancers relates to the environments within which these structures grow, commonly known as the tumor microenvironment.
These microenvironments play a role in facilitating tumor survival, growth, and spread. Tumors can help generate their own infrastructure in the form of vasculature, immune cells, signaling molecules, and extracellular matrices (ECMs), three-dimensional networks of collagen-rich support scaffolding for a cell. ECMs also help regulate cellular communications, and in the tumor microenvironment ECMs can be a key promoter of tumor growth by providing structural support for cancerous cells and in modulating signaling pathways that promote growth.
Now, new research led by the School of Arts & Science’sWei Guo and published in the journal Nature Cell Biology has bridged the complex structural interactions within the tumor microenvironment to the signals that trigger tumor growth. The researchers studied cancerous liver cells grown on ECMs of varying stiffness and discovered that the stiffening associated with tumor growth can initiate a cascade that increases the production of small lipid-encapsulated vesicles known as exosomes.
“Think of these exosomes as packages that each cell couriers out, and, depending on the address, they get directed to other cells,” says Ravi Radhakrishnan, professor of bioengineering in the School of Engineering and Applied Science and a co-author of the paper.
“By recording the number of packages sent, the addresses on these packages, their contents, and most importantly, how they’re regulated and generated, we can better understand the relationship between a patient’s tumor microenvironment and their unique molecular signaling signatures, hinting at more robust personalized cancer therapies,” Radhakrishnan says.
While studying exosomes in relation to tumor growth and metastasis has been well-documented in recent years, researchers have mostly focused on cataloging their characteristics rather than investigating the many processes that govern the creation and shuttling of exosomes between cells. As members of Penn’s Physical Sciences Oncology Center (PSOC), Guo and Radhakrishnan have long collaborated on projects concerning tissue stiffness. For this paper, they sought to elucidate how stiffening promotes exosome trafficking in cancerous intracellular signaling.
“Our lab previously found that high stiffness promotes the secretion of exosomes,” says Di-Ao Liu, co-first author of the paper and a graduate student in the Guo Lab. “Now, we were able to model the stiffening processes through experiments and identify molecular pathways and protein networks that cause this, which better links ECM stiffening to cancerous signaling.”
Alex J. Hughes presents at the BMES CMBE conference in January 2023. (Image credit: Riccardo Gottardi, Assistant Professor in Pediatrics and Bioengineering)
Alex J. Hughes, Assistant Professor in the Department of Bioengineering, was one of thirteen recipients of the 2023 Rising Star Award for Junior Faculty by the Cellular and Molecular Bioengineering (CMBE) Special Interest Group. The Rising Star Award recognizes a CMBE member in their early independent career stage that has made an outstanding impact on the field of cellular and molecular bioengineering. CMBE is a special interest group of the Biomedical Engineering Society (BMES), the premier professional organization of bioengineers.
The Hughes Lab in Penn Bioengineering works to “bring developmental processes that operate in vertebrate embryos and regenerating organs under an engineering control framework” in order to “build better tissues.” Hughes’s research interest is in harnessing the developmental principles of organs, allowing him to design medically relevant scaffolds and machines. In 2020 he became the first Penn Engineering faculty member to receive the Maximizing Investigators’ Research Award (MIRA) from the National Institutes of Health (NIH), and he was awarded a prestigious CAREER Award from the National Science Foundation (NSF) in 2021. Most recently, Hughes’s work has focused on understanding the development of cells and tissues in the human kidney via the creation of “organoids”: miniscule organ models that can mimic the biochemical and mechanical properties of the developing kidney. Understanding and engineering how the kidney functions could open doors to more successful regenerative medicine strategies to address highly prevalent congenital and adult diseases.
Hughes and his fellow award recipients were recognized at the annual BMES CBME conference in Indian Wells, CA in January 2023.
Ravi Radhakrishnan, Professor and Chair of the Department of Bioengineering and Professor in Chemical and Biomolecular Engineering, was named to the 2022 Class of Fellows of the Biomedical Engineering Society (BMES). BMES, the premier society for biomedical engineers in the U.S., recognizes individuals for their accomplishments, significant contributions and service to the Society and the field of biomedical engineering in their annual Class of Fellows. The incoming Fellows were recognized during the BMES annual meeting on October 13, 2022.
Radhakrishnan’s research interests lie at the interface of chemical physics and molecular biology. The Radhakrishnan Lab’s goal is to provide molecular level and mechanistic characterization of biomolecular and cellular systems and formulate quantitatively accurate microscopic models for predicting the interactions of various therapeutic agents with innate biochemical signaling mechanisms. Radhakrishnan was named BE’s Department Chair in January 2020. He is also a member of the Genomics & Computational Biology (GCB) Graduate Group and is the former director of the Penn Institute for Computational Science (PICS).
