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.

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.

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.

Bioengineers on the Brink of Breaching Blood-brain Barrier

by Nathi Magubane

From left: Emily Han, Rohan Palanki, Jacqueline Li, Michael Mitchell, Dongyoon Kim, and Marshall Padilla of Penn Engineering.

Imagine the brain as an air traffic control tower, overseeing the crucial and complex operations of the body’s ‘airport.’ This tower, essential for coordinating the ceaseless flow of neurological signals, is guarded by a formidable layer that functions like the airport’s security team, diligently screening everything and everyone, ensuring no unwanted intruders disrupt the vital workings inside.

However, this security, while vital, comes with a significant drawback: sometimes, a ‘mechanic’—in the form of critical medication needed for treating neurological disorders—is needed inside the control tower to fix arising issues. But if the security is too stringent, denying even these essential agents entry, the very operations they’re meant to protect could be jeopardized.

Now, researchers led by Michael Mitchell of the University of Pennsylvania are broaching this long-standing boundary in biology, known as the blood-brain barrier, by developing a method akin to providing this mechanic with a special keycard to bypass security. Their findings, published in the journal Nano Letters, present a model that uses lipid nanoparticles (LNPs) to deliver mRNA, offering new hope for treating conditions like Alzheimer’s disease and seizures—not unlike fixing the control tower’s glitches without compromising its security.

“Our model performed better at crossing the blood-brain barrier than others and helped us identify organ-specific particles that we later validated in future models,” says Mitchell, associate professor of bioengineering at Penn’s School of Engineering and Applied Science, and senior author on the study. “It’s an exciting proof of concept that will no doubt inform novel approaches to treating conditions like traumatic brain injury, stroke, and Alzheimer’s.”

Read the full story in Penn Today.

Penn Bioengineering Student Kaitlin Mrksich Wins Outstanding Research Award from the Society for Biomaterials

Kaitlin Mrksich, an undergraduate student in Penn Bioengineering, was honored with the Student Award for Outstanding Research (Undergraduate) by the Society for Biomaterials (SFB). This prestigious award recognizes undergraduate students who have shown outstanding achievement in biomaterials research.

Mrksich is a third-year student from Hinsdale, Illinois. She is interested in developing drug delivery systems that can serve as novel therapeutics for a variety of diseases. She works in the lab of Michael Mitchell, Associate Professor in Bioengineering. In the Mitchell Lab, Mrksich investigates the ionizable lipid component of lipid nanoparticles for mRNA delivery.

“In Kaitlin’s independent projects, she has focused on probing the role of lipophilicity and chirality for LNP-mediated mRNA delivery,” Mitchell said in the award announcement. “She has synthesized dozens of unique lipids, formulated these lipids into LNPs, and evaluated their potential for mRNA delivery in vivo and in primary T cells. She has been able to deduce structure-function relationships that help explain the role of lipid hydrophobicity in the delivery of mRNA by LNPs. Her findings have not only been instrumental in helping our lab design better LNPs but will also provide fundamental knowledge that will benefit all labs working on LNP technology.”

In addition to her academic activities, Mrksich is also the President of the Penn Biomedical Engineering Society (BMES), where she plans community-building and professional-development events for bioengineering majors, and the visit coordinator for special programs for the Kite and Key Society, where she organizes virtual programming to introduce prospective students to Penn. She also tutors a West Philadelphia high school student in chemistry as part of the West Philadelphia Tutoring Project and is a member of Tau Beta Pi engineering honor society and Sigma Kappa sorority. After graduating, she plans to pursue an M.D.-Ph.D. in Bioengineering. 

Read the full list of 2024 SFB award recipients here.

Lipid Nanoparticles That Deliver mRNA to T Cells Hold Promise for Autoimmune Diseases

by Janelle Weaver

Ajay Thatte, Benjamin Nachod, Rohan Palanki, Kelsey Swingle, Alex Hamilton, and Michael Mitchell (Left to Right – Courtesy of the Mitchell Lab) 

Autoimmune disorders are among the most prevalent chronic diseases across the globe, affecting approximately 5-7% of the world’s population. Emerging treatments for autoimmune disorders focus on “adoptive cell therapies,” or those using cells from a patient’s own body to achieve immunosuppression. These therapeutic cells are recognized by the patient’s body as ‘self,’ therefore limiting side effects, and are specifically engineered to localize the intended therapeutic effect.

In treating autoimmune diseases, current adoptive cell therapies have largely centered around the regulatory T cell (Treg), which is defined by the expression of the Forkhead box protein 3, orFoxp3. Although Tregs offer great potential, using them for therapeutic purposes remains a major challenge. In particular, current delivery methods result in inefficient engineering of T cells.

Tregs only compose approximately 5-10% of circulating peripheral blood mononuclear cells. Furthermore, Tregs lack more specific surface markers that differentiate them from other T cell populations. These hurdles make it difficult to harvest, purify and grow Tregs to therapeutically relevant numbers. Although there are additional tissue-resident Tregs in non-lymphoid organs such as in skeletal muscle and visceral adipose tissue, these Tregs are severely inaccessible and low in number.

Now, a research team led by Michael Mitchell, Associate Professor in Bioengineering in the School of Engineering and Applied Science at the University of Pennsylvania, has developed a lipid nanoparticle (LNP) platform to deliver Foxp3 messenger RNA (mRNA) to T cells for applications in autoimmunity. Their findings are published in the journal Nano Letters.

“The major challenges associated with ex vivo (outside the body) cell engineering are efficiency, toxicity, and scale-up: our mRNA lipid nanoparticles (mRNA LNPs) allow us to overcome all of these issues,” says Mitchell. “Our work’s novelty comes from three major components: first, the use of mRNA, which allows for the generation of transient immunosuppressive cells; second, the use of LNPs, which allow for effective delivery of mRNA and efficient cell engineering; and last, the ex vivo engineering of primary human T cells for autoimmune diseases, offering the most direct pipeline for clinical translation of this therapy from bench to bedside.”

“To our knowledge, this is one of the first mRNA LNP platforms that has been used to engineer T cells for autoimmune therapies,” he continues. “Broadly, this platform can be used to engineer adoptive cell therapies for specific autoimmune diseases and can potentially be used to create therapeutic avenues for allergies, organ transplantation and beyond.”

Delivering the Foxp3 protein to T cells has been difficult because proteins do not readily cross the cell membrane. “The mRNA encodes for Foxp3 protein, which is a transcription factor that makes the T cells immunosuppressive rather than active,” explains first author Ajay Thatte, a doctoral student in Bioengineering and NSF Fellow in the Mitchell Lab. “These engineered T cells can suppress effector T cell function, which is important as T cell hyperactivity is a common phenotype in autoimmune diseases.”

Read the full story in Penn Engineering Today.

Leveraging the Body’s Postal System to Understand and Treat Disease

by Nathi Magubane

Microwell device with a solution in the reservoir (Image: Courtesy of David E. Reynolds)

Akin to the packages sent from one person to another via an elaborate postal system, cells send tiny parcels that bear contents and packaging material that serve key purposes: To protect the contents from the outside world and to make sure it gets to the right place via a label with an address. 

These packages are known as extracellular vesicles (EVs)—lipid-bound molecules that serve a variety of regulatory and maintenance functions throughout the body. They assist in the removal of unwanted materials within the cell, and they transport proteins, aid in DNA and RNA transfer, and promote tumorigeneses in cancerous cells. 

Given their myriad roles, EVs have taken center stage for many researchers in the biomedical space as they have the potential to improve current methods of disease detection and treatment. The main challenge, however, is accurately identifying the molecular contents of EVs while also characterizing the EVs, which, unlike other cellular components that are more homogenous, have more heterogeneity.

Now, a team of researchers at the University of Pennsylvania has developed a novel platform, droplet-free double digital assay, for not only profiling individual EVs but also accurately discerning their molecular contents. The researchers took the digital assay, which quantifies the contents of a molecule via binary metric—a 1 corresponds to the presence of a molecule and a zero to the lack thereof—and applies it to the EV. The work is published in Advanced Science.

The team was led by Jina Ko, an assistant professor with appointments in the School of Engineering and Applied Science and Perelman School of Medicine. “Our method allows for highly accurate quantification of the individual molecules inside an EV,” Ko says . “This opens up many doors in the realm of early disease detection and treatment.”

The researchers first compartmentalized individual EVs utilizing a microwell approach to isolate the EVs. Next, they captured individual molecules within the EVs and amplified the signal for clarity. The team then was able to determine the expression levels of pivotal EV biomarkers with remarkable precision via fluorescence.

Read the full story in Penn Today.

Jina Ko is an assistant professor in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine and an assistant professor in the Department of Bioengineering in the School of Engineering and Applied Science at the University of Pennsylvania.

David Reynolds is a Ph.D. candidate in the Department of Bioengineering in Penn Engineering.

Other authors include, Menghan Pan, George Galanis, Yoon Ho Roh, Renee-Tyler T. Morales, Shailesh Senthil Kumar, and Su-Jin Heo of the Department of Bioengineering at Penn Engineering; Jingbo Yang and Xiaowei Xu of the Department of Pathology and Laboratory Medicine at Penn Medicine; and Wei Guo of the Department of Biology in the School of Arts & Sciences at Penn.

The research was supported by the National Institutes of Health: grants R00CA256353, R35 GM141832, and CA174523 (SPORE).

Estelle Sunghee Park Appointed Assistant Professor at Purdue University

Estelle Park, Ph.D.

Penn Bioengineering is proud to congratulate Sunghee Estelle Park, Ph.D. on her appointment as Assistant Professor in the Weldon School of Biomedical Engineering at Purdue University. Park earned her Ph.D. at Penn Bioengineering, graduating in July 2023. She conducted doctoral research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering. Her appointment at Purdue will begin January 2024.

During her Ph.D. research, Park forged a unique path that combined principles in developmental biology, stem cell biology, organoids, and organ-on-a-chip technology to develop innovative in vitro models that can faithfully replicate the pathophysiology of various human diseases. Using a microengineered model of the human retina, she discovered previously unknown roles of the MAPK, IL-17, PI3K-AKT, and TGF-β signaling pathways in the pathogenesis of age-related macular degeneration (AMD), presenting novel therapeutic targets that could be further investigated for the development of AMD treatments. More recently, she tackled a significant challenge in the organoid field, the limited tissue growth and maturity in conventional organoid cultures, by designing microengineered systems that enabled organoids to grow with unprecedented levels of maturity and human-relevance. By integrating these platforms with bioinformatics and computational analyses, she identified novel disease-specific biomarkers of inflammatory bowel disease (IBD) and intestinal fibrosis, including previously unknown link between the presence of lncRNA and the development of IBD.

“The unique interdisciplinary expertise I gained from these projects has shaped me into a scholar with a strong collaborative ethos, a quality I hold in high esteem as we work towards advancing our knowledge and management of health and disease,” says Park.

Her vision as an independent researcher is to become a leading faculty who makes impactful contributions to our fundamental understanding of the factors influencing the structural and functional changes of human organs in health and disease. To achieve this, she plans to lead a stem cell bioengineering laboratory with a primary focus on tissue engineering and regenerative medicine. This will involve developing human organoids-on-a-chip systems and establishing next-generation biomedical devices and therapies tailored for regenerative and personalized medicine.

“I am grateful to all my Ph.D. mentors and lab mates at the BIOLines lab and especially my advisor Dr. Dan Huh, for his exceptional guidance, unwavering support, and invaluable mentorship throughout my Ph.D. journey,” says Park. “Dan’s expertise, dedication, and commitment to excellence have been instrumental in shaping both my research and professional development, while also training me to become an independent scientist and mentor.”

Congratulations to Dr. Park from everyone at Penn Bioengineering!

Bioengineering Faculty Member Named ‘Young Innovator’ for Creation of Multiple Myeloma Therapy

by Abbey Porter

Michael Mitchell

Michael J. Mitchell, Associate Professor in Bioengineering at the University of Pennsylvania School of Engineering and Applied Science, has been named a “Young Innovator of Cellular and Molecular Bioengineering” by Cellular and Molecular Bioengineering, the journal of the Biomedical Engineering Society (BMES).

The award recognizes faculty who are conducting some of the most innovative and impactful studies in the field of biomedical engineering. Recipients will present their research and be officially recognized at the BMES Annual Meeting in October.

Mitchell is being honored for creating an RNA nanoparticle therapy that stops the spread of the deadly bone marrow cancer multiple myeloma and helps to eliminate it altogether. Known for being difficult to treat, the disease kills over 100,000 people every year.

“We urgently need innovative, effective therapies against this cancer,” Mitchell says. “The nanotechnology we developed can potentially serve as a platform to treat multiple myeloma and other bone marrow-based malignancies.”

Mitchell, along with Christian Figuerora-Espada, a doctoral student in Bioengineering, previously published a study in PNAS describing how their RNA nanoparticle therapy stops multiple myeloma from moving through the blood vessels and mutating. In their current paper in Cellular and Molecular Bioengineering, which expands upon this RNA nanoparticle platform, they show that inhibition of both multiple myeloma migration and adhesion to bone marrow blood vessels, combined with an FDA-approved multiple myeloma therapeutic, extends survival in a mouse model of multiple myeloma.

Read more in Penn Engineering Today.

Sonura Named Among 2023 PHL Inno Under 25 Honorees

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce

A team of recent Penn Bioengineering graduates have been included in list of prominent young Philadelphia innovators as chosen by The Philadelphia Business Journal and PHL Inno.

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce founded Sonura as their Senior Design Project in Bioengineering. The team, who all graduated in 2023, picked up a competitive President’s Innovation Prize for their beanie that promotes the cognitive and socioemotional development of newborns in the NICU by protecting them from the auditory hazards of their environments while fostering parental connection. Now, they have been included in the list of fourteen Inno Under 25 honorees for 2023.

“To determine this year’s list, the Philadelphia Business Journal and PHL Inno sought nominations from the public and considered candidates put forth by our editorial team. To be considered, nominees must be 25 years of age or younger and work for a company based in Greater Philadelphia and/or reside in the region.

Honorees span a wide range of industries, including consumer goods, biotechnology and environmental solutions. Many are products of the region’s colleges and universities, though some studied farther afield before setting up shop locally.”

Read “Announcing the 2023 PHL Inno Under 25 honorees” and “Inno Under 25” in PHL Inno. Penn affiliates can subscribe through Penn’s library services.