Left to right: Hong-Huy Tran, Chrissie Jaruchotiratanasakul, Manali Mahajan (Photo Courtesy of CiPD)
The Center for Innovation and Precision Dentistry (CiPD), a collaboration between Penn Engineering and Penn Dental Medicine, has partnered with Wharton’s Mack Institute for Innovation Management on a research project which brings robotics to healthcare. More specifically, this project will explore potential uses of nanorobot technology for oral health care. The interdisciplinary partnership brings together three students from different Penn programs to study the commercialization of a new technology that detects and removes harmful dental plaque.
“Our main goal is to bring together dental medicine and engineering for out-of-the-box solutions to address unresolved problems we face in oral health care,” says Hyun (Michel) Koo, Co-Founding Director of CiPD and Professor of Orthodontics. “We are focused on affordable solutions and truly disruptive technologies, which at the same time are feasible and translatable.”
Patients being treated for B-cell non-Hodgkin’s Lymphoma (NHL) who are part of minority populations may not have equal access to cutting-edge CAR T cell therapies, according to a new analysis led by researchers from the Perelman School of Medicine and published in NEJM Evidence.
CAR T cell therapy is a personalized form of cancer therapy that was pioneered at Penn Medicine and has brought hope to thousands of patients who had otherwise run out of treatment options. Six different CAR T cell therapies have been approved since 2017 for a variety of blood cancers, including B-cell NHL that has relapsed or stopped responding to treatment. Image: iStock/PeopleImages
“CAR T cell therapy represents a major leap forward for blood cancer treatment, with many patients living longer than ever before, but its true promise can only be realized if every patient in need has access to these therapies,” says lead author Guido Ghilardi, a postdoctoral fellow in the laboratory of senior author Marco Ruella, an assistant professor of hematology-oncology and scientific director of the Lymphoma Program. “From the scientific perspective, we’re constantly working in the laboratory to make CAR T cell therapy work better, but we also want to make sure that when a groundbreaking treatment like this becomes available, it reaches all patients who might be able to benefit.”
Illustration of the 55LCC complex. (Image: Courtesy of Cameron Baines/Phospho Biomedical Animation)
When cells in the human body divide, they must first make accurate copies of their DNA. The DNA replication exercise is one of the most important processes in all living organisms and is fraught with risks of mutation, which can lead to cell death or cancer. Now, findings from biologists from the Perelman School of Medicine and from the University of Leeds have identified a multiprotein “machine” in cells that helps govern the pausing or stopping of DNA replication to ensure its smooth progress. Illustration of the 55LCC complex. (Image: Courtesy of Cameron Baines/Phospho Biomedical Animation)
The discovery, published in Cell, advances the understanding of DNA replication, helps explain a puzzling set of genetic diseases, and could inform the development of future treatments for neurologic and developmental disorders.
“We’ve found what appears to be a critical quality-control mechanism in cells,” says senior co-corresponding author Roger Greenberg, the J. Samuel Staub, M.D. Professor in the department of Cancer Biology, director of the Penn Center for Genome Integrity, and director of basic science at the Basser Center for BRCA at Penn Medicine. “Trillions of cells in our body divide every single day, and this requires accurate replication of our genomes. Our work describes a new mechanism that regulates protein stability in replicating DNA. We now know a bit more about an important step in this complex biological process.”
“The proposed studies lay the foundation to make a major scientific impact in the childhood leukemia field and ultimately improve outcomes for children,” says Vining.
LeAnn Dourte, Practice Associate Professor in Bioengineering, has been one of the most active members of the Penn Engineering faculty in pioneering the Structured, Active, In-Class Learning (SAIL) model of education. In a recent issue of the Penn Almanac, Dourte boils down her practical advice for faculty looking to make their courses more interactive and dynamic into one simple philosophy: “Just change 10 minutes.”
“The effectiveness of these 10-minute activities hinges on their alignment with learning objectives. Students are always on the lookout for anything that they see as busy-work, so articulating the purpose of such activities is paramount to their success. These are some of the goals I think about when I design activities with my learning objectives in mind. While some of these approaches are specific to subjects with quantitative problem solving, many have applications across disciplines.”
Dourte’s article articulates her active learning approach, along with a list of specific learning objectives, including encouraging diverse perspectives, promoting error recognition and correction, and more.
To commemorate the 50th anniversary of the Department of Bioengineering at the University of Pennsylvania, the department has acquired several pieces of artwork that celebrate the beauty of biological forms. The pieces were curated by Nicole Lampl, Director/Curator of the Reeves House Visual Arts Center.
Created with a limited palette on artist dyed silk and hemp, Vertex makes a strong impression of motion in the branching imagery derived from fractals.
“I went to the fractal show at the New Mexico Museum of Natural History & Science’s planetarium, and it blew my mind,” says Busby. “They go from a picture of the galaxy down to a picture of an atom, and you see the same image repeated again and again.” The artist’s focus on macro imagery is the product of her lifelong fascination with molecular biology. Constantly exploring new materials and techniques from around the world, Busby has purchased batiks from Bali, dupioni from India, and silk from China that she paints and dyes with acid. The artist sees the variety of materials that she used in her mixed media works as a direct reflection of the incredible diversity found among living things.
About Betty Busby: After graduating from the Rhode Island School of Design with a BFA in ceramics, Betty Busby founded a custom ceramic tile manufacturing firm in Los Angeles. After nearly 20 years of running the firm, she sold the business in 1994 (it is still in operation to this day). Upon relocating to New Mexico, she changed the focus of her artwork to fiber, taking it full time in 2004. Her manufacturing background has lead to constant experimentation with new materials and techniques that fuel her work. Originally inspired by Amish quilts at the Kutztown County Fair near her childhood home in Pennsylvania, her work has made the journey from bed quilts to mixed media sculpture, and is constantly evolving and heading in new directions.
Artist Statement: Betty Busby creates fiber art using technological innovations and unconventional materials to create work with inviting textures. She is often inspired by the macro world, exploring the structures and forms of nature. She uses these images as jumping off points to create abstractions, which become ground-breaking works of art. Betty Busby creates fiber art using technological innovations and unconventional materials to create work with inviting texture. But the voice of textile roots is strong with traditional fabric, paints and dyes, needle and thread and her trusty Singer working alongside her iPad and spun bonded nonwoven fibers.
Pseudomonas Aeruginosa Colony Biofilm (2023)
Artist: Scott Chimileski
Photography mounted on board, 24″ W x 16″ H
The most harmful species of microbes build biofilms and swarm together. When the conditions are right, the Pseudomonas Aeruginosa (pictured here), can shift from a harmless bacterium found in many environments to a pathogen that causes infection in burn wounds.
About Scott Chimileski: Scott Chimileski a microbiologist, imaging specialist, and educator based in Woods Hole, MA, where he is a Research Scientist at the Marine Biological Laboratory (MBL). From 2015 to 2019, he was a postdoctoral fellow in the Kolter Lab within the Department of Microbiology at Harvard Medical School. During that time, Roberto Kolter and Chimileski curated the exhibition Microbial Life: A Universe at the Edge of Sight, open at the Harvard Museum of Natural History from February 2018 through March 2022. They also coauthored Life at the Edge of Sight: A Photographic Exploration of the Microbial World, published by Harvard University Press in 2017. Chimileski’s imagery has been published or broadcast by media outlets including National Geographic, WIRED, TIME, The Atlantic, STAT, Fast Company, NPR, The Scientist, Scientific American, Smithsonian Magazine, The Biologist, HHMI Biointeractive, Tangled Bank Studios, Quanta Magazine, the NIH Director’s Blog, WBUR Boston, The Verge, TED Talks, and CBS Sunday Morning. Exhibitions at public venues across the United States, and in Uruguay, Brazil, Colombia, Scotland, the UK, and Denmark have featured his imagery and scientific interpretation. Chimileski received a Passion in Science Award in Arts & Creativity from New England Biolabs in 2016, and FASEB BioArt awards in 2016, 2017, and 2019.
Artist Statement: Chimileski’s original scientific photography specializes in high resolution macrophotography and time lapse imaging of microbial colonies and behaviors. This collection includes photos captured at sites around the world where exceptional natural microbial forms flourish, such as Yellowstone National Park. Most bacterial and archaeal cells are far too small to see with the naked eye. However, microbes are seldom if ever found in isolation. Rather, the biology of the microbial world is underpinned by the tremendous interactivity, sociality and modularity of individual cells, which often coalesce in great numbers to produce macroscopically visible structures, including biofilms, microbial mats, colonies, swarms and fruiting bodies. Chimileski is focused on the development of macroscopic imaging techniques as well as time-lapse photography and three-dimensional scanning technologies as applied to microbial multicellular forms, collective behaviors, communities and interspecies interactions. He is also interested in leveraging the power of photography as a medium for communicating microbiology to other scientists and to the general public.
Amoeba Hex Pod (2018), Amoeba (2013) and Amoeba Coffin (2013)
Artist: Melissa Bolger
Gouache, ink, and graphite on clayboard, 6″ W x 6″ H x 2″ D
Bolger explores Synthetic Biology and the myriad ways in which it can imbue engineered organisms with new abilities. Redesigned and entirely imagined cellular structures coexist and intermingle as the artist investigates an unseen universe. Through her visual exploration of this scientific field, the artist invites us to ponder what the consequences of replicating nature on a cellular level might have on human evolution.
About Melissa Bolger: Melissa Bolger is a California native and was raised outside of Redding, CA where her parents settled on a remote piece of property, built a house, and raised their family off the grid. her mother sewed the family’s clothes and other household items. For Bolger, the woods were her playground and she grew up hiking, fishing, hunting, riding horses and panning for gold. Some of her early artistic influences grew from those days, living off a dirt road overlooking a canyon and creek, when do-it-yourself was the only way to get things done. Today, she merges the techniques of craft with fine art in her interpretative portraits, recycled materials, paintings and drawings. Melissa Bolger’s work has been exhibited in solo and group shows and her work has been reviewed in publications.
Artist Statement: The “Soft Machines” series explores themes of patterns within nature through the intricate application of pen and ink, gouache, and graphite. Her interest is on cellular structures that are manipulated by synthetic and artificial life. Borrowing from nature and science, microscopic shapes and images are drawn and high-key colors painted that float, hover, and drip in visual metaphors that insinuate synthetic manipulation. Patterns of nature are complex on a nanoscale and certain thoughts arise. What would be the consequences of science’s attempt to replicate nature on a cellular level? How far will synthetic operations continue in human history? What effects will they have on evolution? The manipulation of nature at the nanoscopic level is overwhelming, mind-blowing and psychedelic. While this manipulation has the potential to alter human life in numerous uncharted ways the question of how and what form life will survive in a synthetic and artificial way is mysterious, puzzling and hi-tech. Approaching these themes with curiosity and instinct, exploring and documenting the natural and the unnatural together and maintaining a sense of wonderment is the embodiment of “Soft Machines.” Examining the intricacies of the invisible world give birth to patterns that move like a heartbeat, live and survive against all odds. “Soft Machines” is the beginning of a series of work exploring, investigating and examining particular themes around astrobiology, synthetic cellular and molecular reconstruction. Bolger continues to explore themes of patterns within nature on a nanoscopic scale in her intricate application of pen and ink, gouache, graphite and mixed media. The invisible world under a microscope is a fascinating phenomenon that Bolger uses as a stepping point into inner realms of space that move, float, and drip. Whether it be an alien landscape or intricate organic patterns, the diversity of life on the planet is an essential force and fascination within the work.
(From left to right) Breakthrough Prize recipients Drew Weissman, Virginia M-Y Lee, Katalin Karikó, and Carl June at a reception on Feb. 13. (Image: Courtesy of Penn Medicine News)
In popular culture, scientific discovery is often portrayed in “Eureka!” moments of sudden realization: a lightbulb moment, coming sometimes by accident. But in real life—and in Penn Medicine’s rich history as a scientific innovator for more than 250 years—scientific breakthroughs can never truly be distilled down to a single, “ah-ha” moment. They’re the result of years of hard work, perseverance, and determination to keep going, despite repeated, often discouraging, barriers and setbacks.
“Research is [like taking], four, or six, or eight steps back, and then a little stumble forward,” said Drew Weissman, MD, PhD, the Roberts Family Professor of Vaccine Research. “You keep doing that over and over and somehow, rarely, you can get to the top of the step.”
For Weissman and his research partner, Katalin Karikó, PhD, an adjunct professor of Neurosurgery, that persistence—documented in thousands of news stories across the globe—led to the mRNA technology that enabled two lifesaving COVID-19 vaccines, earning the duo numerous accolades, including the highest scientific honor, the 2023 Nobel Prize in Medicine.
Weissman and Karikó were also the 2022 recipients of the Breakthrough Prize in Life Sciences, the world’s largest science awards, popularly known as the “Oscars of Science.” Founded in 2012 by a group of web and tech luminaries including Google co-founder Sergey Brin and Meta CEO Mark Zuckerberg, the Breakthrough Prizes recognize “the world’s top scientists working in the fundamental sciences—the disciplines that ask the biggest questions and find the deepest explanations.” With six total winners, including four from the Perelman School of Medicine (PSOM), Penn stands alongside Harvard and MIT as the institutions whose researchers have been honored with the most Breakthrough Prizes.
Virginia M.–Y. Lee, PhD, the John H. Ware 3rd Professor in Alzheimer’s Research, was awarded the Prize in 2020 for discovering how different forms of misfolded proteins can move from cell to cell and lead to neurodegenerative disease progression. Carl June, MD, the Richard W. Vague Professor in Immunotherapy, is the most recent recipient and will be recognized at a star-studded red-carpet event in April for pioneering the development of CAR T cell therapy, which programs patients’ own immune cells to fight their cancer.
The four PSOM Breakthrough Prize recipients were honored on Tuesday, Feb. 13, 2024, when a new large-scale installation was unveiled in the lobby of the Biomedical Research Building to celebrate each laurate and their life-changing discoveries. During a light-hearted panel discussion, the honorees shared how a clear purpose, dogged determination, and a good sense of humor enabled their momentum forward.
Weissman presented the Department of Bioengineering’s 2022 Herman P. Schwan Distinguished Lecture: “Nucleoside-modified mRNA-LNP therapeutics.” Read more stories featuring Weissman in the BE Blog here.
Every Penn Bioengineering semester culminates in a series of “demo days” — dedicated time in which undergraduate Bioengineering students demonstrate projects made in their Bioengineering lab courses or in Senior Design for their classmates and faculty. These are held in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace (or the Penn BE Labs), the dedicated teaching lab for the Bioengineering Department which also functions as an interdisciplinary bio-makerspace open to the entire Penn community.
For the Fall 2023 demos, Popular Mechanics paid a visit to the BE Labs to witness the (in)famous “cockroach lab,” a staple of the third year course “Bioengineering, Modeling, Analysis, and Design Laboratory” (affectionately known as BE MAD). This year’s cockroach demos featured a miniature Taylor Swift — flaunting a cockroach limb — and several projects featuring the faces of course faculty, David Meaney, Solomon R. Pollack Professor in Bioengineering and Senior Associate Dean in Penn Engineering, and Michael Patterson, Director of Educational Laboratories in Bioengineering.
3d illustration of a damaged and disintegrating cancer cell. (Image: iStock/vitanovski)
The development of any type of second cancer following CAR T cell therapy is a rare occurrence, as found in an analysis of more than 400 patients treated at Penn Medicine, researchers from the Perelman School of Medicine at the University of Pennsylvania reported today in Nature Medicine. The team also described a single case of an incidental T cell lymphoma that did not express the CAR gene and was found in the lymph node of a patient who developed a secondary lung tumor following CAR T cell therapy.
CAR T cell therapy, a personalized form of immunotherapy in which each patient’s T cells are modified to target and kill their cancer cells, was pioneered at Penn. More than 30,000 patients with blood cancers in the United States—many of whom had few, if any, remaining treatment options available—have been treated with CAR T cell therapy since the first such therapy was approved in 2017. Some of the earliest patients treated in clinical trials have gone on to experience long-lasting remissions of a decade or more.
Secondary cancers, including T cell lymphomas, are a known, rare risk of several types of cancer treatment, including chemotherapy, radiation, and stem cell transplant. CAR T cell therapy is currently only approved to treat blood cancers that have relapsed or stopped responding to treatment, so patients who receive CAR T cell therapies have already received multiple other types of treatment and are facing dire prognoses.
In November 2023, the FDA announced an investigation into several reported cases of secondary T cell malignancies, including CAR-positive lymphoma, in patients who previously received CAR T cell therapy products. In January 2024, the FDA began requiring drugmakers to add a safety label warning to CAR T cell products. While the FDA review is still ongoing, it remains unclear whether the secondary T cell malignancies were caused by CAR T cell therapy.
As a leader in CAR T cell therapy, Penn has longstanding, clearly established protocols to monitor each patient both during and after treatment – including follow-up for 15 years after infusion – and participates in national reporting requirements and databases that track outcomes data from all cell therapy and bone marrow transplants.
Marco Ruella, M.D.
“When this case was identified, we did a detailed analysis and concluded the T cell lymphoma was not related to the CAR T cell therapy. As the news of other cases came to light, we knew we should go deeper, to comb through our own data to better understand and help define the risk of any type of secondary cancer in patients who have received CAR T cell products,” said senior author Marco Ruella, MD, an assistant professor of Hematology-Oncology and Scientific Director of the Lymphoma Program. “What we found was very encouraging and reinforces the overall safety profile for this type of personalized cell therapy.”
A pair of proteins, YAP and TAZ, has been identified as conductors of bone development in the womb and could provide insight into genetic diseases such as osteogenesis imperfecta, known commonly as “brittle bone disease.” This research, published in Developmental Cell and led by members of the McKay Orthopaedic Research Laboratory of the Perelman School of Medicine, adds understanding to the field of mechanobiology, which studies how mechanical forces influence biology.
“Despite more than a century of study on the mechanobiology of bone development, the cellular and molecular basis largely has remained a mystery,” says the study’s senior author, Joel Boerckel, an associate professor of orthopaedic surgery. “Here, we identify a new population of cells that are key to turning the body’s early cartilage template into bone, guided by the force-activated gene regulating proteins, YAP and TAZ.”
