With OCTOPUS, Dan Huh’s team has significantly advanced the frontiers of organoid research, providing a platform superior to conventional gel droplets. OCTOPUS splits the soft hydrogel culture material into a tentacled geometry. The thin, radial culture chambers sit on a circular disk the size of a U.S. quarter, allowing organoids to advance to an unprecedented degree of maturity.
When it comes to human bodies, there is no such thing as typical. Variation is the rule. In recent years, the biological sciences have increased their focus on exploring the poignant lack of norms between individuals, and medical and pharmaceutical researchers are asking questions about translating insights concerning biological variation into more precise and compassionate care.
What if therapies could be tailored to each patient? What would happen if we could predict an individual body’s response to a drug before trial-and-error treatment? Is it possible to understand the way a person’s disease begins and develops so we can know exactly how to cure it?
Dan Huh, Associate Professor in the Department of Bioengineering at the University of Pennsylvania’s School of Engineering and Applied Science, seeks answers to these questions by replicating biological systems outside of the body. These external copies of internal systems promise to boost drug efficacy while providing new levels of knowledge about patient health.
An innovator of organ-on-a-chip technology, or miniature copies of bodily systems stored in plastic devices no larger than a thumb drive, Huh has broadened his attention to engineering mini-organs in a dish using a patient’s own cells.
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.
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.
Penn Integrates Knowledge Professor Kevin Johnson takes the stage at 24th Engaging Minds. (Image: Ben Asen)
This past weekend in New York City, the University of Pennsylvania showcased its 24th Engaging Minds event, the first in person since 2019. It was hosted by Penn Alumni.
Three Penn Integrates Knowledge University Professors — Kevin Johnson, Lance Freeman and Dolores Albarracín, — each discussed their research. The audience, at least 600 in person and remote, heard about using city planning to promote racial equity, about how conspiracy theories come to life and propagate, and about the need for physicians to communicate effectively with patients and families.
Following brief remarks from Penn Alumni President Ann Reese, University President Liz Magill introduced the event. “As many of you know, I’ve been thinking a lot and speaking often about what makes Penn Penn,” she said. “What are our distinctive strengths? What are the unique contributions to society that we have made in the past and can make in the future? And where do we go from the extraordinary position we are in now?”
Magill went on to express gratitude for the speakers and invited the audience to think about how the researchers’ work and expertise furthered what she described as the “twin principles of truth and opportunity.”
He took the audience through his family history, education and training, pausing at a point on the timeline when he was a young physician-scientist who had just explained a new medical topic to a journalist. “I felt really good about the conversation — and then the article came out,” Johnson said.
In the piece, he had been cast as saying that the medical community was over-treating this condition, “which is not what I said.” He realized in that moment that as a physician, he had been taught to communicate what a study finds, not how to act based on those findings. That experience shifted his thinking on how to communicate scientific topics, and he has spent decades trying to move the needle on how others in his field perceive this.
“As scientists we face obstacles. We face the obstacle of scale, so, small projects that we’re asked to generalize. We face the issue of trust. And then we face the issue of values,” Johnson said. “I’ll add a fourth, which is format; the way we choose to reach specific audiences will be different.”
Read more about the 24th Engaging Minds at Penn Today.
Kevin Johnson is the David L. Cohen University of Pennsylvania Professor in the Departments of Biostatistics, Epidemiology and Informatics and Computer and Information Science. As a Penn Integrates Knowlegde (PIK) University Professor, Johnson also holds appointments in the Departments of Bioengineering and Pediatrics, as well as in the Annenberg School of Communication.
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).
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.
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.
We hope you will join us for the 2022 Grace Hopper Distinguished Lecture by Dr. Jennifer Lewis, presented by the Department of Bioengineering and hosted by Dani S. Bassett, J. Peter Skirkanich Professor in Bioengineering, Electrical and Systems Engineering, Physics & Astronomy, Neurology and Psychiatry.
Date: Thursday, December 8, 2022
Start Time: 3:30 PM EST
Location: Glandt Forum, Singh Center for Nanotechnology, 3205 Walnut Street, Philadelphia, PA 19104
Join us after the live lecture for a light reception!
Daphna Shohamy, Ph.D.
Speaker: Daphna Shohamy, Ph.D.
Kavli Professor of Brain Science, Co-Director of the Kavli Institute for Brain Science, Professor in the Department of Psychology & Zuckerman Mind Brain Behavior Institute Columbia University
From robots to humans, the ability to learn from experience turns a rigid response system into a flexible, adaptive one. In the past several decades, major advances have been made in understanding how humans and other animals learn from experience to make decisions. However, most of this progress has focused on rather simple forms of stimulus-response learning, such as automatic responses or habits. In this talk, I will turn to consider how past experience guides more complex decisions, such as those requiring flexible reasoning, inference, and deliberation. Across a range of behavioral contexts, I will demonstrate a critical role for memory in such decisions and will discuss how multiple brain regions interact to support learning, what this means for how memories are used, and the consequences for how decisions are made. Uncovering the pervasive role of memory in decision-making challenges the way we think about what memory is for, suggesting that memory’s primary purpose may be to guide future behavior and that storing a record of the past is just one way to do so.
Dr. Shohamy Bio:
Daphna Shohamy, PhDis a professor at Columbia University where she co-directs the Kavli Center for Neural Sciences and is Associate Director of the Zuckerman Mind, Brain Behavior Institute. Dr. Shohamy’s work focuses on the link between memory, and decision-making. Combining brain imaging in healthy humans with studies of patients with neurological and psychiatric disorders, Dr. Shohamy seeks to understand how the brain transforms experiences into memories; how memories shape decisions and actions; and how motivation and exploration affect human behavior.
Information on the GraceHopper Lecture: In support of its educational mission of promoting the role of all engineers in society, the School of Engineering and Applied Science presents the GraceHopper Lecture Series. This series is intended to serve the dual purpose of recognizing successful women in engineering and of inspiring students to achieve at the highest level.
Rear Admiral GraceHopper was a mathematician, computer scientist, systems designer and the inventor of the compiler. Her outstanding contributions to computer science benefited academia, industry and the military. In 1928 she graduated from Vassar College with a B.A. in mathematics and physics and joined the Vassar faculty. While an instructor, she continued her studies in mathematics at Yale University where she earned an M.A. in 1930 and a Ph.D. in 1934. GraceHopper is known worldwide for her work with the first large-scale digital computer, the Navy’s Mark I. In 1949 she joined Philadelphia’s Eckert-Mauchly, founded by the builders of ENIAC, which was building UNIVAC I. Her work on compilers and on making machines understand ordinary language instructions lead ultimately to the development of the business language, COBOL. GraceHopper served on the faculty of the Moore School for 15 years, and in 1974 received an honorary degree from the University. In support of the accomplishments of women in engineering, each department within the School invites a prominent speaker for a one or two-day visit that incorporates a public lecture, various mini-talks and opportunities to interact with undergraduate and graduate students and faculty.
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,”
An infographic explains the magnetic and catalytic properties of the iron oxide nanoparticles and their assembly into bristle and floss-like forms. (Image: Melissa Pappas/Penn Engineering)
Koo shared findings from one of his recent studies conducted in collaboration with Penn Engineering, which showed that a shapeshifting robotic microswarm can brush and floss teeth.
“Routine oral care is cumbersome and can pose challenges for many people, especially those who have a hard time cleaning their teeth” says Koo. “You have to brush your teeth, then floss your teeth, then rinse your mouth; it’s a manual, multistep process. The big innovation here is that the robotics system can do all three in a single, hands-free, automated way.”
The building blocks of these microrobots are iron oxide nanoparticles that have both catalytic and magnetic activity. Using a magnetic field, researchers could direct their motion and configuration to form either bristlelike structures that sweep away dental plaque from the broad surfaces of teeth, or elongated strings that can slip between teeth like a length of floss.
“Nanoparticles can be shaped and controlled with magnetic fields in surprising ways,” says Edward Steager, a senior research investigator at Penn Engineering and co-corresponding author. “We form bristles that can extend, sweep, and even transfer back and forth across a space, much like flossing. The way it works is similar to how a robotic arm might reach out and clean a surface. The system can be programmed to do the nanoparticle assembly and motion control automatically.”
