Perelman School of Medicine (PSOM) professors and Penn Bioengineering Graduate Group members Carl June and Avery Posey are leading the charge in T cell therapy and the fight against cancer.
Avery Posey, PhDCarl June, MD
Advances in genome editing through processes such as CRISPR, and the ability to rewire cells through synthetic biology, have led to increasingly elaborate approaches for modifying and supercharging T cells for therapy. Avery Posey, Assistant Professor of Pharmacology, and Carl June, the Richard W. Vague Professor in Immunotherapy, explain how new techniques are providing tools to counter some of the limitations of current CAR T cell therapies in a recent Nature feature.
The pair were also part of a team of researchers from PSOM, the Children’s Hospital of Philadelphia (CHOP), and the Corporal Michael J. Crescenz VA Medical Center to receive an inaugural $8 million Therapy ACceleration To Intercept CAncer Lethality (TACTICAL) Award from the Prostate Cancer Foundation. Their project will develop new clinic-ready CAR T cell therapies for Metastatic Castrate-Resistant Prostate Cancer (mCRPC).
Penn Engineering’s newly established ASSET Center aims to make AI-enabled systems more “safe, explainable and trustworthy” by studying the fundamentals of the artificial neural networks that organize and interpret data to solve problems.
ASSET’s first funding collaboration is with Penn’s Perelman School of Medicine (PSOM) and the Penn Institute for Biomedical Informatics (IBI). Together, they have launched a series of seed grants that will fund research at the intersection of AI and healthcare.
Teams featuring faculty members from Penn Engineering, Penn Medicine and the Wharton School applied for these grants, to be funded annually at $100,000. A committee consisting of faculty from both Penn Engineering and PSOM evaluated 18 applications and judged the proposals based on clinical relevance, AI foundations and potential for impact.
Artificial intelligence and machine learning promise to revolutionize nearly every field, sifting through massive amounts of data to find insights that humans would miss, making faster and more accurate decisions and predictions as a result.
Applying those insights to healthcare could yield life-saving benefits. For example, AI-enabled systems could analyze medical imaging for hard-to-spot tumors, collate multiple streams of disparate patient information for faster diagnoses or more accurately predict the course of disease.
Given the stakes, however, understanding exactly how these technologies arrive at their conclusions is critical. Doctors, nurses and other healthcare providers won’t use such technologies if they don’t trust that their internal logic is sound.
“We are developing techniques that will allow AI-based decision systems to provide both quantifiable guarantees and explanations of their predictions,” says Rajeev Alur, Zisman Family Professor in Computer and Information Science and Director of the ASSET Center. “Transparency and accuracy are key.”
“Development of explainable and trustworthy AI is critical for adoption in the practice of medicine,” adds Marylyn Ritchie, Professor of Genetics and Director of the Penn Institute for Biomedical Informatics. “We are thrilled about this partnership between ASSET and IBI to fund these innovative and exciting projects.”
Seven projects were selected in the inaugural class, including projects from Dani S. Bassett, J. Peter Skirkanich Professor in the Departments of Bioengineering, Electrical and Systems Engineering, Physics & Astronomy, Neurology, and Psychiatry, and several members of the Penn Bioengineering Graduate Group: Despina Kontos, Matthew J. Wilson Professor of Research Radiology II, Department of Radiology, Penn Medicine and Lyle Ungar, Professor, Department of Computer and Information Science, Penn Engineering; Spyridon Bakas, Assistant Professor, Departments of Pathology and Laboratory Medicine and Radiology, Penn Medicine; and Walter R. Witschey, Associate Professor, Department of Radiology, Penn Medicine.
Optimizing clinical monitoring for delivery room resuscitation using novel interpretable AI
Elizabeth Foglia, Associate Professor, Department of Pediatrics, Penn Medicine and the Children’s Hospital of Philadelphia
Dani S. Bassett, J. Peter Skirkanich Professor, Departments of Bioengineering and Electrical and Systems Engineering, Penn Engineering
This project will apply a novel interpretable machine learning approach, known as the Distributed Information Bottleneck, to solve pressing problems in identifying and displaying critical information during time-sensitive clinical encounters. This project will develop a framework for the optimal integration of information from multiple physiologic measures that are continuously monitored during delivery room resuscitation. The team’s immediate goal is to detect and display key target respiratory parameters during delivery room resuscitation to prevent acute and chronic lung injury for preterm infants. Because this approach is generalizable to any setting in which complex relations between information-rich variables are predictive of health outcomes, the project will lay the groundwork for future applications to other clinical scenarios.
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.
From left to right: Marc Singer, Kirsten Leute, D. Kacy Cullen, Dan Huh, Doug Smith, and Haig Aghajanian
Two Penn Bioengineering Professors have received awards in the 7th Annual Celebration of Innovation from the Penn Center for Innovation (PCI).
Dongeun (Dan) Huh, Associate Professor in the Department of Bioengineering, was named the 2022 Inventor of the Year. D. Kacy Cullen, Associate Professor of Neurosurgery with a secondary appointment in Bioengineering, accepted the Deal of the Year Award on behalf of his company Innervace along with Co-Scientific Founder Douglas H. Smith, Robert A. Groff Professor of Teaching and Research in Neurosurgery in the Perelman School of Medicine.
PCI is interdisciplinary center for technology commercialization and startups in the Penn community. Their 7th Annual Celebration, held on December 6, 2022 at the Singh Center for Nanotechnology, honored Penn researchers and inventors whose achievements were a particular highlight of the fiscal year.
Huh was honored in recognition of his “extraordinary innovations in bioengineering tools.” The Huh Biologically Inspired Engineering Systems Laboratory (BIOLines) Laboratory is a leader in tissue engineering and cell-based smart biomedical devices, particularly in the “lab-on-a-chip” field of devices which can approximate the functioning of organs. Their research has been featured by the National Science Foundation (NSF, video below) and Wired, and has received a competitive Chan Zuckerberg Initiative (CZI) grant. Most recently, their “implantation-on-a-chip” technology has been used to better understand early-stage pregnancy. Huh and former lab member Andrei Georgescu (Ph.D. in Bioengineering, 2021) founded the spinoff company Vivodyne to bring this organ-on-a-chip technology to the industry sector. Fast Company included Vivodyne in a list of “most innovative” companies.
Innervace, represented by Cullen and Smith, took home the Deal of the Year award in recognition of its “successful Series A funding.” Innervace is another Penn spinoff which develops “anatomically inspired living scaffolds for brain pathway reconstruction.” Innervace raised up to $40 million in Series A financing to “accelerate a new cell therapy modality for the treatment of neurological disorders.” The Cullen Lab at Penn Medicine combines neuroengineering, regenerative medicine, and the study of neurotrauma to improve understanding of neural injury and develop cutting-edge neural tissue engineering-based treatments to promote regeneration and restore function.
Read the full list of 2022 PCI Award winners here.
The 2022 iGEM team from left to right: June Ahn, Shreya Villimanalan, Adiva Daniar, Wangari Mbuthia, Cristina Perez and Moses Zeidan.
Congratulations to the 2022 University of Pennsylvania iGEM Team who took home a gold medal in the iGEM Grand Jamboree. This international competition of multidisciplinary teams of graduate and undergraduate students presenting original projects in synthetic biology culminated in the in-person Jamboree event held in Paris, France in October 2022. Over 370 judges awarded prizes and medals to the 350+ teams representing over 40 countries.
The 2022 Penn team was awarded a Gold Medal for their project “Photocreate,” a toolbox to control intercellular communication using optogenetics. Their plasmid constructs are designed to control protein secretion, display and shedding using a photocleavable protein, Phocl. The full abstract reads:
Intercellular communication is primarily studied using synthetic protein-level circuits. These circuits currently lack the spatial and temporal control necessary for targeted and time-sensitive applications. To address this gap, we developed Photocrete, a toolbox of protein constructs for light-inducible control of protein display, secretion, and shedding. We expanded upon RELEASE (Vlahos et al.), a modular and generalizable protein circuit which utilizes an ER retention motif and an exogenous protease to control protein secretion. We optogenetically modified RELEASE by replacing different components with the photocleavable protein PhoCl, allowing us to control the mammalian secretion pathway at distinct nodes with finely-tuned light administration regimens. Preliminary results indicate integration of Photocrete into the secretion pathway, but more research is necessary to determine optimal light administration settings. The potential for high spatial and temporal control of Photocrete could allow researchers to perform various signaling studies and develop therapeutics at a new level of precision.
The 2022 iGEM team includes undergraduates June Ahn (B.S. in Biochemistry, Physics and Nutrition), Adiva Daniar (B.S.E. in Bioengineering, minor in Engineering Entrepreneurship), Wangari Mbuthia (B.S.E. in Bioengineering), Cristina Perez (B.S.E. in Bioengineering, minor in Physics), Shreya Vallimanalan (B.S.E. in Bioengineering, minor in Computational Neuroscience), an d Moses Zeidan (B.S.E. in Bioengineering, minor in Chemistry and Spanish). They were mentored by graduate students David Gonzalez-Martinez, Gabrielle Ho, Zikang Huang, and Will Benman. Their faculty advisor is Lukasz Bugaj, Assistant Professor in Bioengineering.
Read the full results of the 2022 iGEM Competition here.
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).
Penn Bioengineering alumnus Jiaqi Liu has been named to the eighth class of Schwarzman Scholars and will enroll at Tsinghua University in Beijing in August.
The program’s core curriculum focuses on leadership, China, and global affairs, according to the Schwarzman program. The academic program is updated each year to align with current and future geopolitical priorities. The coursework, cultural immersion, and personal and professional development opportunities are designed to equip students with an understanding of China’s changing role in the world.
This year, approximately 151 Schwarzman Scholars were selected from a pool of 3,000 applicants from 36 countries and 121 universities.
Jiaqi Liu earned his master’s degree in bioengineering in the School of Engineering and Applied Science in 2021. After graduation, he returned to China and works in global early-stage Venture Capital. According to the Schwarzman Scholars program, Liu is passionate about promoting medical equality and affordable health care solutions and has experience in medtech startup, global pharmaceutical company, health care consulting, and health care venture capital.
This story is by Amanda Mott. Read more about the Schwarzman Scholars at Penn Today.
The Heilmeier Award honors a Penn Engineering faculty member whose work is scientifically meritorious and has high technological impact and visibility. It is named for the late George H. Heilmeier, a Penn Engineering alumnus and member of the School’s Board of Advisors, whose technological contributions include the development of liquid crystal displays and whose honors include the National Medal of Science and Kyoto Prize.
Bassett, who also holds appointments in Physics & Astronomy in Penn Arts & Sciences and in Neurology and Psychiatry in the Perelman School of Medicine, is a pioneer in the field of network neuroscience, an emerging subfield which incorporates elements of mathematics, physics, biology and systems engineering to better understand how the overall shape of connections between individual neurons influences cognitive traits. They lead the Complex Systems lab, which tackles problems at the intersection of science, engineering and medicine using systems-level approaches, exploring fields such as curiosity, dynamic networks in neuroscience, and psychiatric disease.
Bassett will deliver the 2022-23 Heilmeier Award Lecture in Spring 2023.
Eight researchers from the Perelman School of Medicine have received research grants designed to invest in high-risk, high-reward projects.
Bushra Raj, Assistant Professor of Cell and Developmental Biology in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group, was one of three Penn winners of the NIH Director’s New Innovator Award for independent projects developed by early-career investigators. More additional Penn scientists who received NIH Director’s Transformative Research Award for a project focusing on cancer research.
Raj’s project focuses on “testing a novel technology that uses CRISPR/Cas gene-editing tools to genomically record inputs from two signaling pathways in the developing zebrafish brain.”
Established in 2009, the Transformative Research Award promotes cross-cutting, interdisciplinary science and is open to individuals and teams of investigators who propose research that could potentially create or challenge existing paradigms.
“Padilla came to the CiPD training program earlier this year with a Ph.D. in Chemistry from the University of Wisconsin-Madison. He is currently a postdoctoral fellow in the lab of Dr. Michael J. Mitchell of Penn’s Department of Bioengineering, where his research focuses on developing new materials to enhance the efficacy and safety of biological therapeutics. While passionate about research, he also has a strong interest in developing mentoring relationships and in teaching. At Wisconsin, Marshall earned a certificate in research, teaching, and learning, in which he conducted a research project on developing positive metacognitive practices in introductory organic chemistry. Additionally, he taught a course on mentoring in a research setting, and is passionate about promoting diversity and inclusiveness in biomedical sciences.”
