A Moonshot for Obesity: New Molecules, Inspired by Space Shuttles, Advance Lipid Nanoparticle Delivery for Weight Control

by Ian Scheffler

Like space shuttles using booster rockets to breach the atmosphere, lipid nanoparticles (LNPs) equipped with the new molecule more successfully deliver medicinal payloads. (Love Employee via Getty Images)

Inspired by the design of space shuttles, Penn Engineering researchers have invented a new way to synthesize a key component of lipid nanoparticles (LNPs), the revolutionary delivery vehicle for mRNA treatments including the Pfizer-BioNTech and Moderna COVID-19 vaccines, simplifying the manufacture of LNPs while boosting their efficacy at delivering mRNA to cells for medicinal purposes.

In a paper in Nature Communications, Michael J. Mitchell, Associate Professor in the Department of Bioengineering, describes a new way to synthesize ionizable lipidoids, key chemical components of LNPs that help protect and deliver medicinal payloads. For this paper, Mitchell and his co-authors tested delivery of an mRNA drug for treating obesity and gene-editing tools for treating genetic disease. 

Previous experiments have shown that lipidoids with branched tails perform better at delivering mRNA to cells, but the methods for creating these molecules are time- and cost-intensive. “We offer a novel construction strategy for rapid and cost-efficient synthesis of these lipidoids,” says Xuexiang Han, a postdoctoral student in the Mitchell Lab and the paper’s co-first author. 

Read the full story in Penn Engineering Today.

Beyond Bias: The Annual Women in Data Science Conference Unites Women across Penn

by Ian Scheffler

Lasya Sreepada, a doctoral student in Bioengineering (BE), addresses the crowd. (Image: Lamont Abrams)

In Invisible Women: Data Bias in a World Designed for Men, Caroline Criado Perez notes that the default perspective for virtually all data collection and analysis is male. (Hence crash test dummies being designed to mimic male bodies, air conditioning systems relying on a model of the male metabolism, and women’s unique heart attack symptoms other than chest pain — like nausea and back pain — often going unrecognized, even by women experiencing them.)

Nearly a decade ago, a group of women at Stanford decided to address this issue by convening a one-day technical conference on data science; that meeting has now grown into a worldwide movement, with hundreds of sister conferences each year — a tradition in which Penn Engineering is proud to take part.

By 2030, Women in Data Science (WiDS), the non-profit that spun out of that early meeting, hopes to achieve 30% representation of women in data science globally. For Susan Davidson, Weiss Professor in Computer and Information Science (CIS) and a co-chair of the annual WiDS @ Penn conference, the benefits of participating in WiDS go beyond just networking. “To see women who are successful in your field is extremely encouraging,” says Davidson.

This year, Penn Engineering partnered with Analytics at Wharton (AAW) and the Penn Museum to co-host the fifth annual WiDS @ Penn conference, bringing together dozens of women from across the University and beyond to learn about the latest applications of data science in topics as diverse as online education and health care.

“It gave me the opportunity to not only show others what it means to be a data scientist,” says Lasya Sreepada, a doctoral student in Bioengineering, who presented her work studying early-onset Alzheimer’s disease using large data sets, “but also what it means to be a woman applying data science to integrate multiple disciplines spanning neuroscience, genomics and radiology.”

Penn Engineering students from all levels of their academic careers participated, from Aashika Vishwanath, a sophomore in CIS, president of the Wharton Undergraduate Data Analytics Club and senior data science consultant at Wharton Analytics Fellows, who shared her work developing an AI-powered teaching assistant, to Betty Xu, a master’s student in Electrical and Systems Engineering, who collaborated with the Wharton Neuroscience Initiative to study financial decision making. “Data can help us know the unknown in every field,” says Xu. “You can be a great data scientist no matter your background.”

Read the full story in Penn Engineering Today.

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.


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

“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.

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.