Alex Hughes Named CMBE Rising Star

A collage of photos: Alex Hughes presenting, the title slide of his presentation with the title "Interpreting geometric rules of early kidney formation for synthetic morphogenesis," and his acknowledgements slides.
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.

Read the full list of 2023 CMBE Award Winners.

CAR T Cell Therapy Reaches Beyond Cancer

Penn Medicine researchers laud the early results for CAR T therapy in lupus patients, which point to broader horizons for the use of personalized cellular therapies.

Penn Medicine’s Carl June and Daniel Baker.

Engineered immune cells, known as CAR T cells, have shown the world what personalized immunotherapies can do to fight blood cancers. Now, investigators have reported highly promising early results for CAR T therapy in a small set of patients with the autoimmune disease lupus. Penn Medicine CAR T pioneer Carl June and Daniel Baker, a doctoral student in cell and molecular biology in the Perelman School of Medicine, discuss this development in a commentary published in Cell.

“We’ve always known that in principle, CAR T therapies could have broad applications, and it’s very encouraging to see early evidence that this promise is now being realized,” says June, who is the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine at Penn Medicine and director of the Center for Cellular Immunotherapies at the Abramson Cancer Center.

T cells are among the immune system’s most powerful weapons. They can bind to, and kill, other cells they recognize as valid targets, including virus-infected cells. CAR T cells are T cells that have been redirected, through genetic engineering, to efficiently kill specifically defined cell types.

CAR T therapies are created out of each patient’s own cells—collected from the patient’s blood, and then engineered and multiplied in the lab before being reinfused into the patient as a “living drug.” The first CAR T therapy, Kymriah, was developed by June and his team at Penn Medicine, and received Food & Drug Administration approval in 2017. There are now six FDA-approved CAR T cell therapies in the United States, for six different cancers.

From the start of CAR T research, experts believed that T cells could be engineered to fight many conditions other than B cell cancers. Dozens of research teams around the world, including teams at Penn Medicine and biotech spinoffs who are working to develop effective treatments from Penn-developed personalized cellular therapy constructs, are examining these potential new applications. Researchers say lupus is an obvious choice for CAR T therapy because it too is driven by B cells, and thus experimental CAR T therapies against it can employ existing anti-B-cell designs. B cells are the immune system’s antibody-producing cells, and, in lupus, B cells arise that attack the patient’s own organs and tissues.

This story is by Meagan Raeke. Read more at Penn Medicine News.

Carl June is a member of the Penn Bioengineering Graduate Group. Read more stories featuring June’s research here.

Two Penn Bioengineering Professors Receive PCI Innovation Awards

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.

Read more stories featuring Dan Huh and D. Kacy Cullen.

2022 Penn iGEM Team Wins Gold Medal in Grand Jamboree

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.

Work for the annual iGEM competition is conducted in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace.

We acknowledge financial support from the Bradley Gabel Memorial Fund.

Ravi Radhakrishnan Named to the 2022 BMES Class of Fellows

Ravi Radhakrishnan, PhD

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).

Read the announcement and the full 2022 BMES Award Winners and Fellows here.

‘Organ-on-a-Chip’ Device Provides New Insights into Early-Stage Pregnancy

by Scott Harris

Dan Huh’s BIOLines Lab develops several different kinds of organ-on-a-chip systems, such as this blinking-eye-on-a-chip.

If you’d read about it in a science fiction novel, you might not have believed it. Human organs and organ systems — from lungs to blood vessels to blinking eyes — bio-miniaturized and stored on a plastic chip no larger than a matchbook.

But that’s the breathing, blinking reality at the Biologically Inspired Engineering Systems (BIOLines) Laboratory in the Department of Bioengineering in the School of Engineering and Applied Sciences at the University of Pennsylvania, a bona fide pioneer of what is now widely known as “organ-on-a-chip” technology. Proponents hope these devices can one day help scientists around the world learn more about the body’s inner workings and ultimately improve disease prevention and treatment.

“The century-old practice of cell culture is to grow living cells isolated from the human body in hard plastic dishes and keep them bathed in copious amounts of culture media under static conditions, and that is drastically different than the complex, dynamic environment of native tissues in which these cell reside,” said Dan Dongeun Huh, Ph.D., BIOLines’ principal investigator and an associate professor of Bioengineering in Penn’s School of Engineering and Applied Science. “What makes this organ-on-a-chip technology so unique and powerful is that it enables us to reverse-engineer living human tissues using microengineered devices and mimic their intricate biological interactions and physiological functions in ways that have not been possible using traditional cell culture techniques. This represents a major advance in our ability to model and understand the inner workings of complex physiological systems in the human body.”

Generally speaking, organ-on-a-chip devices are made of clear silicone rubber — the same material used to make contact lenses — and can vary in size and design. Embedded within are microfabricated three-dimensional chambers lined with different human cell types, arranged and propagated to ultimately form a structure complex enough to actually mimic the essential elements of a functioning organ.

With partners at the Perelman School of Medicine, BIOLines recently developed a newer variation of the organ-on-a-chip: one that replicates the interface between maternal tissue and the cells of the placenta at the critical moments in early pregnancy when the embryo is implanting in the uterus. Huh and Penn Medicine physicians led a study using the “implantation-on-a-chip” to observe things that would otherwise have been virtually unobservable.

The study findings appeared this spring in the journal Nature Communications.

Continue reading at Penn Medicine News.

Student Spotlight: Bella Mirro

Bella Mirro (BE 2023)

Bella Mirro, a fourth year student in Bioengineering who also minors in Chemistry, spoke with 34th Street Magazine about her many roles at Penn, including being Co–President of Shelter Health Outreach Program (SHOP), a Research Assistant in lab of Michal A. Elovitz, the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health at Penn Medicine, and a Penn Engineering Council Marketing Team Member. In this Q&A, she discusses her research in women’s health and her passions for accessible healthcare, serving Philadelphia’s homeless community, and good food.

Read “Ego of the Week: Bella Mirro” in 34th Street.

Listen: ‘Curious Minds’ on NPR’s ‘Detroit Today’

by Ebonee Johnson

Twin siblings and scholars Dani S. Bassett of Penn and Perry Zurn of American University collaborated over half a dozen years to write “Curious Minds: The Power of Connection.” (Image: Tony and Tracy Wood Photography)

Twin academics Dani S. Basset, J. Peter Skirkanich Professor and director of the Complex Systems Lab, and Perry Zurn, a professor of philosophy at American University, were recently featured as guests on NPR radio show “Detroit Today” to discuss their new book, “Curious Mind: The Power of Connection.”

In their book, Basset and Zurn draw on their previous research, as well as an expansive network of ideas from philosophy, history, education and art to explore how and why people experience curiosity, as well as the different types it can take.

Basset, who holds appointments in the Departments of Bioengineering and Electrical and Systems Engineering, as well as the Department of Physics and Astronomy in Penn Arts & Science, and the Departments of Neuroscience and Psychiatry in Penn Perelman’s School of Medicine, and Zurn spoke with “Detroit Today” producer Sam Corey about what types of things make people curious, and how to stimulate more curiosity in our everyday lives.

According to the twin experts, curiosity is not a standalone facet of one’s personality. Basset and Zurn’s work has shown that a person’s capacity for inquiry is very much tied to the overall state of their health.

“There’s a lot of scientific research focusing on intellectual humility and also openness to ideas,” says Bassett. “And there are really interesting relationships between someone’s openness to ideas, someone’s intellectual humility and their curiosity and also their wellbeing or flourishing,”

Listen to “What makes people curious and how to encourage the act” at “Detroit Today.”

Register for a book signing event for “Curious Minds: The Power of Connection,” on Friday, December 9th at the Penn Bookstore.

This story originally appeared in Penn Engineering Today.

Penn Bioengineering Senior Discusses Remote Research Experience

Yi-An Hsieh (BE 2023)

Yi-An Hsieh, a fourth year Bioengineering student from Anaheim, California, worked remotely this summer on a team that spanned three labs, including the Kamoun Lab at the Hospital of the University of Pennsylvania. Hsieh credits her research on kidney graft failure with enriching her scientific skill set, exposing her to machine learning and real-time interaction with genetic datasets. In a guest post for the Career Services Blog, Hseih writes about her remote summer internship experience. “It showed me that this type of research energy that could not be dampened despite the distance,” she writes.

Read “Exploring How Amino Acid Polymorphisms Affect Graft Survival” in the Career Services Blog.

Bushra Raj Receives NIH Grant Through High-risk, High-reward Research Program

Bushra Raj, Ph.D.

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.

Read the full list of grant recipients in Penn Medicine News.