Tag: bioengineering

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Penn Bioengineering Celebrates the Art in Engineering

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.

Read a message from Department Chair Dr. Ravi Radhakrishnan: “Penn Bioengineering: The Past, Present and Future“

Vertex (2019)

Artist: Betty Busby

Fiber, 66″ W x 56″ H

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.

Links:

Betty Busby:
Website: bbusbyarts.com
Instagram: @bbusbyarts

Scott Chimileski:
Website: scottchimileskiphotography.com/
Instagram: @socialmicrobes

Melissa Bolger:
Website: melissalouisebolger.com
Instagram: @melissalouisebolger

Nicole Lampl
Website: nicolelampl.crevado.com
Instagram: @thecuriouscurator_nicole
Email: njlampl@gmail.com
Phone: 504-428-8589

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“Switchable” Bispecific Antibodies Pave Way for Safer Cancer Treatment

by Nathi Magubane

Bispecific T cell engagers are emerging as a powerful class of immunotherapy to treat cancer but are sometimes hindered by unwanted outcomes, such as on-target, off-tumor toxicity; cytokine release syndrome; and neurotoxicity. Now, researchers Penn researchers have developed a novel “switchable” bispecific T cell engager that mitigates these negative effects by co-opting a drug already approved by the FDA. (Image: iStock / CIPhotos)

In the ever-evolving battle against cancer, immunotherapy presents a turning point. It began with harnessing the body’s immune system to fight cancer, a concept rooted more than a century ago but only gaining significant momentum in recent years. Pioneering this shift were therapies like CAR T cell therapy, which reprograms a patient’s T cells to attack cancer cells. Within this domain, bispecific T cell engagers, or bispecific antibodies, have emerged as effective treatments for many blood-borne cancers in the clinic and are being evaluated for solid tumor therapy.

These antibodies simultaneously latch onto both a cancer cell and a T cell, effectively bridging the gap between the two. This proximity triggers the T cells to unleash their lethal arsenal, thereby killing the cancer cells. However, bispecific T cell engagers, like many cancer therapies, face hurdles such as cell-specific targeting limitations, known as on-target off-tumor toxicity, which means the tumor is correctly targeted but so are other healthy cells in the body, leading to healthy tissue damage. Moreover, bispecific antibodies may also lead to immune system overactivation, a precursor for cytokine release syndrome (CRS), and neurotoxicity.

Now, researchers led by Michael Mitchell of the University of Pennsylvania have found a way to circumvent many of these deleterious effects by developing a bispecific T cell nanoengager that is equipped with an “off switch.” Their findings are published in Nature Biomedical Engineering.

“We’re excited to show that bispecific antibodies can be tweaked in a way that allows us to tap into their powerful cancer-killing potential without inducing toxicity to healthy tissues,” says Mitchell, associate professor of bioengineering at Penn’s School of Engineering and Applied Science. “This new controllable drug-delivery mechanism, which we call switchable bispecific T cell nanoengagers, or SiTEs, adds this switchable component to the antibody via administering an FDA-approved small-molecule drug, amantadine.”

Read the full story in Penn Today.

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Jenny Jiang Wins CZI Grant to Investigate the Potential Trigger for Neurodegenerative Diseases

Jenny Jiang, Ph.D.

TDP-43 may be one of the most dangerous proteins in the human body, implicated in neurodegenerative conditions like ALS and Alzheimer’s disease. But the protein remains mysterious: how TDP-43 interacts with the immune system, for instance, is still unclear. 

Now, Ning Jenny Jiang, J. Peter and Geri Skirkanich Associate Professor of Innovation in Bioengineering, has been selected for the Collaborative Pairs Pilot Project Awards, sponsored by the Chan Zuckerberg Initiative (CZI), to investigate the relationship between TDP-43 and the immune system. 

Launched in 2018, the Collaborative Pairs Pilot Project Awards support pairs of investigators to explore “innovative, interdisciplinary approaches to address critical challenges in the fields of neurodegenerative disease and fundamental neuroscience.” Professor Jiang will partner with Pietro Fratta, MRC Senior Clinical Fellow and MNDA Lady Edith Wolfson Fellow at the University College London Queen Square Institute of Neurology.

The TDP-43 protein is associated with neurodegenerative diseases affecting the central nervous system, including ALS and Alzehimer’s disease. While the loss of neurons and muscle degeneration cause the progressive symptoms, the diseases themselves may be a previously unidentified trigger for abnormal immune system activity. 

One possible link is the intracellular mislocalization of TDP-43 (known as TDP-43 proteinopathy), when the protein winds up in the wrong location, which the Jiang and Fratta Labs will investigate. Successfully proving this link could result in potentially game-changing new therapies for these neurodegenerative diseases. 

The Jiang Lab at Penn Engineering specializes in systems immunology, using high-throughput sequencing and single-cell and quantitative analysis to understand how the immune system develops and ages, as well as the molecular signatures of immune related diseases. Jiang joined Penn Bioengineering in 2021. 

Since arriving on campus, Jiang has teamed with the recently formed Penn Anti-Cancer Engineering Center (PACE), which seeks to understand the forces that determine how cancer grows and spreads, and Engineers in the Center for Precision Engineering (CPE4H), which focuses on innovations in diagnostics and delivery in the development of customizable biomaterials and implantable devices for individualized care. 

Jiang was elected a member of the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows in 2021, and has previously won multiple prestigious awards including the NSF CAREER, a Cancer Research Institute Lloyd J. Old STAR Award, and a CZI Neurodegeneration Challenge Network Ben Barres Early Career Acceleration Award.

Jiang is a leader in high-throughput and high-dimensional analysis of T cells, a type of white blood cell crucial to the functioning of a healthy immune system. A recent study in Nature Immunology described the Jiang Lab’s TetTCR-SeqHD technology, the first approach to provide a multifaceted analysis of antigen-specific T cells in a high-throughput manner.

The CZI Collaborative Pairs Pilot Project Awards will provide $200,000 of funding over 18 months with a chance to advance to the second phase of $3.2 million in funding over a four-year period. 

Read the full list of grantees on the CZI’s Neurodegeneration Challenge Network (NDCN) Projects website here.

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New Chip Opens Door to AI Computing at Light Speed

by Ian Scheffler

Computing at the speed of light may reduce the energy cost of training AI. (Narongrit Doungmanee via Getty Images)

Penn Engineers have developed a new chip that uses light waves, rather than electricity, to perform the complex math essential to training AI. The chip has the potential to radically accelerate the processing speed of computers while also reducing their energy consumption.

The silicon-photonic (SiPh) chip’s design is the first to bring together Benjamin Franklin Medal Laureate and H. Nedwill Ramsey Professor Nader Engheta’s pioneering research in manipulating materials at the nanoscale to perform mathematical computations using light — the fastest possible means of communication — with the SiPh platform, which uses silicon, the cheap, abundant element used to mass-produce computer chips.

The interaction of light waves with matter represents one possible avenue for developing computers that supersede the limitations of today’s chips, which are essentially based on the same principles as chips from the earliest days of the computing revolution in the 1960s.

In a paper in Nature Photonics, Engheta’s group, together with that of Firooz Aflatouni, Associate Professor in Electrical and Systems Engineering, describes the development of the new chip. “We decided to join forces,” says Engheta, leveraging the fact that Aflatouni’s research group has pioneered nanoscale silicon devices.

Their goal was to develop a platform for performing what is known as vector-matrix multiplication, a core mathematical operation in the development and function of neural networks, the computer architecture that powers today’s AI tools.

Read the full story in Penn Engineering Today.

Nader Engheta is the H. Nedwill Ramsey Professor in Electrical and Systems Engineering, Bioengineering, Materials Science and Engineering, and in Physics and Astronomy.

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What Makes a Breakthrough? “Eight Steps Back” Before Making it to the Finish Lit

by Meagan Raeke

(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. 

Read the full story in Penn Medicine News.

Carl June and Jon Epstein are members of the Penn Bioengineering Graduate Group. Read more stories featuring them in the BE Blog here and here, respectively.

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.

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Illuminating the Invisible: Bringing the Smallest Protein Clusters into Focus

by Ian Scheffler

The bright white spots represent tiny clusters of proteins detected by CluMPS. (Photo by: Thomas Mumford)

Penn Engineers have pioneered a new way to visualize the smallest protein clusters, skirting the physical limitations of light-powered microscopes and opening new avenues for detecting the proteins implicated in diseases like Alzheimer’s and testing new treatments.

In a paper in Cell Systems, Lukasz Bugaj, Assistant Professor in Bioengineering, describes the creation of CluMPS, or Clusters Magnified by Phase Separation, a molecular tool that activates by forming conspicuous blobs in the presence of target protein clusters as small as just a few nanometers. In essence, CluMPS functions like an on/off switch that responds to the presence of clusters of the protein it is programmed to detect.

Normally, says Bugaj, detecting such clusters requires laborious techniques. “With CluMPS, you don’t need anything beyond the standard lab microscope.” The tool fuses with the target protein to form condensates orders of magnitude larger than the protein clusters themselves that resemble the colorful blobs in a lava lamp. “We think the simplicity of the approach is one of its main benefits,” says Bugaj. “You don’t need specialized skills or equipment to quickly see whether there are small clusters in your cells.”

Read the full story in Penn Engineering Today.

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Penn Bioengineering Cockroach Lab Featured in Popular Mechanics

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.

Read “How Severed Cockroach Legs Could Help Us ‘Fully Rebuild’ Human Bodies” in Popular Mechanics.

Read more stories featuring the Penn BE Labs in the BE Blog here.

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Researchers Breathe New Life into Lung Repair

by Nathi Magubane

Image: iStock/Mohammed Haneefa Nizamudeen

In the human body, the lungs and their vasculature can be likened to a building with an intricate plumbing system. The lungs’ blood vessels are the pipes essential for transporting blood and nutrients for oxygen delivery and carbon dioxide removal. Much like how pipes can get rusty or clogged, disrupting normal water flow, damage from respiratory viruses, like SARS-CoV-2 or influenza, can interfere with this “plumbing system.”

In a recent study, researchers looked at the critical role of vascular endothelial cells in lung repair. Their work, published in Science Translational Medicine, was led by Andrew Vaughan of the University of Pennsylvania’s School of Veterinary Medicine and shows that, by using techniques that deliver vascular endothelial growth factor alpha (VEGFA) via lipid nanoparticles (LNPs), that they were able to greatly enhance modes of repair for these damaged blood vessels, much like how plumbers patch sections of broken pipes and add new ones.

“While our lab and others have previously shown that endothelial cells are among the unsung heroes in repairing the lungs after viral infections like the flu, this tells us more about the story and sheds light on the molecular mechanisms at play,” says Vaughan, assistant professor of biomedical sciences at Penn Vet. “Here we’ve identified and isolated pathways involved in repairing this tissue, delivered mRNA to endothelial cells, and consequently observed enhanced recovery of the damaged tissue. These findings hint at a more efficient way to promote lung recovery after diseases like COVID-19.”

They found VEGFA’s involvement in this recovery, while building on work in which they used single cell RNA sequencing to identify transforming growth factor beta receptor 2 (TGFBR2) as a major signaling pathway. The researchers saw that when TGFBR2 was missing it stopped the activation of VEGFA. This lack of signal made the blood vessel cells less able to multiply and renew themselves, which is vital for the exchange of oxygen and carbon dioxide in the tiny air sacs of the lungs.

“We’d known there was a link between these two pathways, but this motivated us to see if delivering VEGFA mRNA into endothelial cells could improve lung recovery after disease-related injury,” says first author Gan Zhao, a postdoctoral researcher in the Vaughan Lab.

The Vaughan Lab then reached out to Michael Mitchell of the School of Engineering and Applied Science, whose lab specializes in LNPs, to see if delivery of this mRNA cargo would be feasible.

“LNPs have been great for vaccine delivery and have proven incredibly effective delivery vehicles for genetic information. But the challenge here was to get the LNPs into the bloodstream without them heading to the liver, which is where they tend to congregate as its porous structure lends favor to substances passing from the blood into hepatic cells for filtration,” says Mitchell, an associate professor of bioengineering at Penn Engineering and a coauthor of the paper. “So, we had to devise a way to specifically target the endothelial cells in the lungs.”

Lulu Xue, a postdoctoral researcher in the Mitchell Lab and a co-first author of the paper, explains that they engineered the LNP to have an affinity for lung endothelial cells, this is known as extra hepatic delivery, going beyond the liver.

Read the full story in Penn Today.

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Secondary Cancers Following CAR T Cell Therapy Are Rare, Penn Medicine Analysis Shows

by Meagan Raeke

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.”

Read the full story in Penn Medicine News.

Marco Ruella is Assistant Professor of Medicine in the Perelman School of Medicine. He is a member of the Penn Bioengineering Graduate Group.

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Building Tiny Organs

by David Levin

Dan Huh, Ph.D. (Photo credit: Leslie Barbaro)

More than 34 million Americans suffer from pulmonary diseases like asthma, emphysema and chronic bronchitis. While medical treatments can keep these ailments in check, there are currently no cures. Part of the reason, notes Dan Huh, is that it’s incredibly hard to study how these diseases actually work. While researchers can grow cells taken from human lungs in a dish, they cannot expect them to act like they would in the body. In order to mimic the real deal, it’s necessary to recreate the complex, 3D environment of the lung — right down to its tiny air sacs and blood vessels — and to gently stretch and release the tissue to simulate breathing.

Huh, Associate Professor in Bioengineering, is the cofounder of Vivodyne, a Penn Engineering biotech spinoff that is creating tissues like these in the lab. Vivodyne uses a bioengineering technology that Huh has been developing for more than a decade. While a postdoctoral fellow at Harvard’s Wyss Institute, he played a central role in creating a novel device called an “organ on a chip,” which, as the name implies, assembles multiple cell types on a tiny piece of engineered plastic to create an approximation of an organ.

“While those chips represented a major innovation,” says Huh, “they still weren’t truly lifelike. They lacked many of the essential features of their counterparts in the human body, such as the network of blood vessels running between different kinds of tissue, which are essential for transporting oxygen, nutrients, waste products and various biochemical signals.”

Read the full article in the Fall 2023 issue of the Penn Engineering Magazine.