Penn Engineering is proud to announce the establishment of the Madison “Maddie” Magee Award for Undergraduate Excellence, named in honor of the memory of Madison “Maddie” N. Magee, who graduated with both a bachelor’s degree in Mechanical Engineering and Applied Mechanics (MEAM) and a master’s degree in Bioengineering (BE) in 2021. Following her time at Penn, Maddie joined the Integrative Baseball Performance department of the Philadelphia Phillies, where she collaborated with a group in developing the next generation of baseball players by analyzing biomechanics data.
To establish this award, 130 donors, including the Philadelphia Phillies, came together in 2022 to raise over $50,000, meaning that undergraduate students will be able to receive this award in perpetuity. Recipients will be Penn Engineering seniors who “exemplify the energy, enthusiasm, and excellence that was Maddie.”
“Maddie was full of life and promise and brought unmatched passion and spirit to everything she did,” says Kevin T. Turner, Professor and Chair of MEAM. “It was impossible to not see the impact that she was having on our Department and the School.” Magee excelled as a student at Penn, working as a Teaching Assistant at both Penn and Drexel and providing countless hours of tutoring to fellow students.
It is with deep gratitude for Maddie’s profound and lasting impact on many students, faculty and staff that this award is established.
Maddie passed away while hiking the Pacific Crest Trail on May 28, 2022.
The research team from left to right includes Kelsey Swingle, Hannah Safford, Alex Hamilton, Ajay Thatte, Hannah Geisler, and Mike Mitchell.
New research on reproductive health demonstrates the first successful delivery of mRNA to placental cells to treat pre-eclampsia at its root.
Pre-eclampsia is a leading cause of stillbirths and prematurity worldwide, occurring in 3 – 8 % of pregnancies. A disorder characterized by high maternal blood pressure, it results from insufficient vasodilation in the placenta, restricting blood flow from the mother to the fetus.
Currently, a health-care plan for someone with pre-eclampsia involves diet and movement changes, frequent monitoring, blood pressure management, and sometimes early delivery of the baby. These standards of care address symptoms of the condition, not the root cause, and further perpetuate health inequity.
Now, Penn engineers are addressing this longstanding gap in reproductive health care with targeted RNA therapy.
The COVID vaccines demonstrated how lipid nanoparticles (LNPs) efficiently deliver mRNA to target cells. The success of LNPs is opening doors for a variety of RNA therapies aiming to treat the root causes of illness and disease. However, drug development and health care have consistently neglected a portion of the population in need of targeted care the most – pregnant people and their babies.
In one of the first studies of its kind, published in the Journal of the American Chemical Society,Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering, and Kelsey Swingle, Ph.D. student in the Mitchell Lab and lead author, describe their development of an LNP with the ability to target and deliver mRNA to trophoblasts, endothelial cells, and immune cells in the placenta.
Once these cells receive the mRNA, they create vascular endothelial growth factor (VEGF), a protein that helps expand the blood vessels in the placenta to reduce the mother’s blood pressure and restore adequate circulation to the fetus. The researchers’ successful trials in mice may lead to promising treatments for pre-eclampsia in humans.
Savan Patel, a fourth year Penn Bioengineering student, is one of 42 finalists competing for a 2023 Hertz Fellowship in applied science, mathematics, and engineering, one of the most prestigious Ph.D. fellowships in the United States. Chosen annually, the Hertz Fellowship is awarded to the nation’s most promising graduate students in science and technology.
“Since 1963, the Hertz Foundation has granted fellowships empowering the nation’s most promising young minds in science and technology. Hertz Fellows receive five years of funding valued at up to $250,000, which offers flexibility from the traditional constraints of graduate training and the independence needed to pursue research that best advances our security and economic vitality […]
Over the foundation’s 60-year history of awarding fellowships, more than 1200 Hertz Fellows have established a remarkable track record of accomplishments. Their ranks include two Nobel laureates; recipients of 10 Breakthrough Prizes and three MacArthur Foundation “genius awards”; and winners of the Turing Award, the Fields Medal, the National Medal of Technology, and the National Medal of Science. In addition, 50 are members of the National Academies of Sciences, Engineering and Medicine, and 34 are fellows of the American Association for the Advancement of Science. Hertz Fellows hold over 3,000 patents, have founded more than 375 companies and have created hundreds of thousands of science and technology jobs.”
Patel is studying Bioengineering and Finance in the Jerome Fisher Program in Management and Technology (M&T), an interdisciplinary dual degree program coordinated by Penn Engineering and the Wharton School of Business. He is currently a member of the lab of Michael J. Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in Bioengineering. Patel’s research interests lie at the interface of drug delivery and immunoengineering. His current project involves the use of modified cholesterol molecules to induce shifts in the biodistribution of ionizable lipid nanoparticles (LNPs). Following graduation, he intends to pursue a Ph.D. in bioengineering in which hopes to develop translatable immunotherapies and drug delivery platforms.
If chosen, the Hertz Fellowship will fund Patel’s graduate studies. Selected from over 750 applicants, Patel is one of fifteen undergraduates and one of two bioengineering students to make the final round of interviews. After a culminating round of interviews, the 2023 Class of Hertz Fellows will be announced in May.
Learn more about the Hertz Fellowship and read the full list of finalists here.
Sevile Mannickarottu, Director of Educational Labs, Penn Bioengineering
Sevile Mannickarottu, Director of Educational Laboratories in the Department of Bioengineering (BE), was interviewed in a recent episode of Shifting Schools, a weekly podcast that hosts educators and thought-leaders in conversations about the latest trends in education and EdTech. Mannickarottu, a Penn Engineering alumnus, runs the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, also known as the Penn BE Labs. In addition to being the primary teaching lab for Penn Bioengineering, the Penn BE Labs has grown into “the world’s only interdisciplinary Bio-MakerSpace.”
MakerSpaces–collaborative, educational work environments–have recently grown in popularity. Penn BE Labs distinguishes itself as a Bio-MakerSpace, embracing the interdisciplinary character of bioengineering by offering itself freely as a space for both academic and personal projects. It is stocked with tools ranging from 3D printers, laser cutters, and electrical equipment, including supplies to support work in molecular biology, physiology, chemistry, and microfluidics.
In the episode, hosts Tricia Friedman and Jeff Utecht talk with Mannickarottu about the organic process by which the Penn BE Labs evolved from a standard teaching space for undergraduate engineering laboratory courses into a student-driven hub of creativity and entrepreneurial spirit that is open to the entire Penn community regardless of discipline or major.
Mannickarottu and his team have found that “creativity needs to let go of control – that’s when fun things happen.” As the lab staff and faculty started to allow more creative freedom in the undergraduate bioengineers’ education, the requests for more supplies started pouring in and the lab’s activities and resources grew. “Honestly, we’re driven almost entirely by student requests and student demands,” says Mannickarottu. So when a student requested a sewing machine for a project? They went out and bought one, adding to their ever-growing stockpile of tools. Over time, more and more diverse projects have emerged from the BE Labs, many of them going on to win awards and grow beyond Penn’s campus as independent startups.
In case this sounds out of reach for smaller institutions, Mannickarottu shares words of encouragement. “The biggest thing,” he says, “is to allow for creativity on the part of the students.” A lab or program can start their own MakerSpace surprisingly inexpensively and build their inventory over time. His number one recommendation for those looking to replicate the success of Penn BE Labs is to allow students freedom to innovate, and administrators will be drawn to invest in the MakerSpace to allow for even more opportunities for them to create and thrive.
To help others get started, the Penn BE Labs staff have put a wide range of resources online, including extensive video and photo archives, FAQ’s, tutorials, information about student projects and startups, and equipment inventories. A 2019 post written for the BE Blog by BE alumna Sophie Burkholder (BSE ‘20 & MSE ‘21) gives the reader tips on “how to build your own MakerSpace for under $1500.”
Though it may currently be “the world’s only interdisciplinary Bio-MakerSpace,” the greatest legacy of the Penn BE Labs would be to be known as the first of many.
Listen to “The legacy of your lab” in Shifting Schools to learn more about the Penn BE Labs and for tips on starting your own MakerSpace.
Artist-in-residence and visiting scholar Rebecca Kamen has blended AI and art to produce animated illustrations representing how a dyslexic brain interprets information.
A work that Penn artist-in-residence Rebecca Kamen produced for the show, “Dyslexic Dictionary” at Arion Press in San Francisco. Here, she reinterprets Ph.D. candidate Dale Zhou’s network visualization. (Image: Cat Fennell)
Communicating thoughts with words is considered a uniquely human evolutionary adaptation known as language processing. Fundamentally, it is an information exchange, a lot like data transfer between devices, but one riddled with discrete layers of complexity, as the ways in which our brains interpret and express ideas differ from person to person.
Learning challenges such as dyslexia are underpinned by these differences in language processing and can be characterized by difficulty learning and decoding information from written text.
Artist-in-residence in Penn’s Department of Physics and Astronomy Rebecca Kamen has explored her personal relationship with dyslexia and information exchange to produce works that reflect elements of both her creative process and understanding of language. Kamen unveiled her latest exhibit at Arion Press Gallery in San Francisco, where nine artists with dyslexia were invited to produce imaginative interpretations of learning and experiencing language.
The artists were presented with several prompts in varying formats, including books, words, poems, quotes, articles, and even a single letter, and tasked with creating a dyslexic dictionary: an exploration of the ways in which their dyslexia empowered them to engage in information exchange in unique ways.
Undiagnosed dyslexia
“[For the exhibit], each artist selected a word representing the way they learn, and mine was ‘lens,’” explains Kamen. “It’s a word that captures how being dyslexic provides me with a unique perspective for viewing and interacting with the world.”
From an early age, Kamen enjoyed learning about the natural sciences and was excited about the process of discovery. She struggled, however, with reading at school, which initially presented an obstacle to achieving her dreams of becoming a teacher. “I had a difficult time getting into college,” says Kamen. “When I graduated high school, the word ‘dyslexia’ didn’t really exist, so I assumed everyone struggled with reading.”
Kamen was diagnosed with dyslexia well into her tenure as a professor. “Most dyslexic people face challenges that may go unnoticed by others,” she says, “but they usually find creative ways to overcome them.”
This perspective on seeing and experiencing the world through the lens of dyslexia not only informed Kamen’s latest work for the exhibition “Dyslexic Dictionary,” but also showcased her background in merging art and science. For decades, Kamen’s work has investigated the intersection of the two, creating distinct ways of exploring new relationships and similarities.
“Artists and scientists are curious creatures always looking for patterns,” explains Kamen. “And that’s because patterns communicate larger insights about the world around us.”
The researchers studied different information-seeking approaches by monitoring how participants explore Wikipedia pages and categorically related these to two ideas rooted in philosophical understandings of learning: a “busybody,” who typically jumps between diverse ideas and collects loosely connected information; and a more purpose-driven “hunter,” who systematically ties in closely related concepts to fill their knowledge gaps.
They used these classifications to inform their computational model, the knowledge network. This uses text and context to determine the degree of relatedness between the Wikipedia pages and their content—represented by dots connected with lines of varying thickness to illustrate the strength of association.
In an adaption of the knowledge network, Kamen was classified as a dancer, an archetype elaborated on in an accompanying review paper by Dale Zhou, a Ph.D. candidate in Bassett’s Complex Systems Lab, who had also collaborated with Kamen on “Reveal.”
“The dancer can be described as an individual that breaks away from the traditional pathways of investigation,” says Zhou. “Someone who takes leaps of creative imagination and in the process, produces new concepts and radically remodels knowledge networks.”
Dani Smith Bassett is J. Peter Skirkanich Professor in Bioengineering with secondary appointments in the Departments of Physics & Astronomy, Electrical & Systems Engineering, Neurology, and Psychiatry.
David Lydon-Staley is an Assistant Professor in the Annenberg School for Communications and Bioengineering and is an alumnus of the Bassett Lab.
The model of tubule packing developed by the Hughes Lab shows the tubules repelling each other and shifting around.
A recent study by Penn Bioengineering researchers sheds new light on the role of physics in kidney development. The kidney uses structures called nephrons and tubules to filter blood and pass urine to the bladder. Nephron number is set at birth and can vary over an order of magnitude (anywhere from 100,000 to over a million nephrons in an individual kidney). While the reasons for this variability remain unclear, low numbers of nephrons predispose patients to hypertension and chronic kidney disease.
Now, research published in Developmental Cell led by Alex J. Hughes, Assistant Professor in the Department of Bioengineering, demonstrates a new physics-driven approach to better visualize and understand how a healthy kidney develops to avoid organizational defects that would impair its function. While previous efforts have typically approached this problem using molecular genetics and mouse models, the Hughes Lab’s physics-based approach could link particular types of defects to this genetic information and possibly highlight new treatments to prevent or fix congenital defects.
Alex J. Hughes, Assistant Professor in Bioengineering
Louis Prahl, NIH F32 Postodctoral Fellow
During embryonic development, kidney tubules grow and the tips divide to make a branched tree with clusters of nephron stem cells surrounding each branch tip. In order to build more nephrons, the tree needs to grow more branches. To keep the branches from overlapping, the kidney’s surface grows more crowded as the number of branches increase. “At this point, it’s like adding more people to a crowded elevator,” says Louis Prahl, first author of the paper and Postdoctoral Fellow in the Hughes Lab. “The branches need to keep rearranging to accommodate more until organ growth stops.”
To understand this process, Hughes, Prahl and their team investigated branch organization in mouse kidneys as well as using computer models and a 3D printed model of tubules. Their results show that tubules have to actively restructure – essentially divide at narrower angles – to accommodate more tubules. Computer simulations also identified ‘defective’ packing, in which the simulation parameters caused tubules to either overlap or be forced beneath the kidney surface. The team’s experimentation and analysis of published studies of genetic mouse models of kidney disease confirmed that these defects do occur.
This study represents a unique synthesis of different fields to understand congenital kidney disease. Mathematicians have studied geometric packing problems for decades in other contexts, but the structural features of the kidney present new applications for these models. Previous models of kidney branching have approached these problems from the perspective of individual branches or using purely geometric models that don’t account for tissue mechanics. By contrast, The Hughes Lab’s computer model demonstrates the physics of how tubule families interact with each other, allowing them to identify ‘phases’ of kidney organization that either relate to normal kidney development or organizational defects. Their 3D printed model of tubules shows that these effects can occur even when one sets the biology aside.
Hughes has been widely recognized for his research in the understanding of kidney development. This new publication is the first fruit of his 2021 CAREER Award from the National Science Foundation (NSF) and he was recently named a 2023 Rising Star by the Cellular and Molecular Bioengineering (CMBE) Special Interest Group. In 2020 he became the first Penn Engineering faculty member to receive the Maximizing Investigators’ Research Award (MIRA) from the National Institutes of Health (NIH) for his forward-thinking work in the creation of new tools for tissue engineering.
Pediatric nephrologists have long worked to understand the cause of these childhood kidney defects. These efforts are often confounded by a lack of evidence for a single causative mutation. The Hughes Lab’s approach presents a new and different application of the packing problem and could help answer some of these unsolved questions and open doors to prevention of these diseases. Following this study, Hughes and his lab members will continue to explore the physics of kidney tubule packing, looking for interesting connections between packing organization, mechanical stresses between neighboring tubule tips, and nephron formation while attempting to copy these principles to build stem cell derived tissues to replace damaged or diseased kidney tissue. Mechanical forces play an important role in developmental biology and there is much scope for Hughes, Prahl and their colleagues to learn about these properties in relation to the kidney.
Other authors include Bioengineering Ph.D. students and Hughes Lab members John Viola and Jiageng Liu.
This work was supported by NSF CAREER 2047271, NIH MIRA R35GM133380, Predoctoral Training Program in Developmental Biology T32HD083185, and NIH F32 fellowship DK126385.
Members of the research team include (from left to right) Xuexiang Han, Michael J. Mitchell, Ningqiang Gong, Lulu Xue, Sarah J. Shepherd, and Rakan El-Mayta.
Since the success of the COVID-19 vaccine, RNA therapies have been the object of increasing interest in the biotech world. These therapies work with your body to target the genetic root of diseases and infections, a promising alternative treatment method to that of traditional pharmaceutical drugs.
Lipid nanoparticles (LNPs) have been successfully used in drug delivery for decades. FDA-approved therapies use them as vehicles for delivering messenger RNA (mRNA), which prompts the cell to make new proteins, and small interfering RNA (siRNA), which instruct the cell to silence or inhibit the expression of certain proteins.
The biggest challenge in developing a successful RNA therapy is its targeted delivery. Research is now confronting the current limitations of LNPs, which have left many diseases without an effective RNA therapy.
Liver fibrosis occurs when the liver is repeatedly damaged and the healing process results in the accumulation of scar tissue, impeding healthy liver function. It is a chronic disease characterized by the buildup of excessive collagen-rich extracellular matrix (ECM). Liver fibrosis has remained challenging to treat using RNA therapies due to a lack of delivery systems for targeting activated liver-resident fibroblasts. Both the solid fibroblast structure and the lack of specificity or affinity to target these fibroblasts has impeded current LNPs from entering activated liver-resident fibroblasts, and thus they are unable to deliver RNA therapeutics.
To tackle this issue and help provide a treatment for the millions of people who suffer from this chronic disease, Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, and postdoctoral fellows Xuexiang Han and Ningqiang Gong, found a new way to synthesize ligand-tethered LNPs, increasing their selectivity and allowing them to target liver fibroblasts.
Lulu Xue, Margaret Billingsley, Rakan El-Mayta, Sarah J. Shepherd, Mohamad-Gabriel Alameh and Drew Weissman, Roberts Family Professor in Vaccine Research and Director of the Penn Institute for RNA Innovation at the Perelman School of Medicine, also contributed to this work.
With OCTOPUS, Dan Huh’s team has significantly advanced the frontiers of organoid research, providing a platform superior to conventional gel droplets. OCTOPUS splits the soft hydrogel culture material into a tentacled geometry. The thin, radial culture chambers sit on a circular disk the size of a U.S. quarter, allowing organoids to advance to an unprecedented degree of maturity.
When it comes to human bodies, there is no such thing as typical. Variation is the rule. In recent years, the biological sciences have increased their focus on exploring the poignant lack of norms between individuals, and medical and pharmaceutical researchers are asking questions about translating insights concerning biological variation into more precise and compassionate care.
What if therapies could be tailored to each patient? What would happen if we could predict an individual body’s response to a drug before trial-and-error treatment? Is it possible to understand the way a person’s disease begins and develops so we can know exactly how to cure it?
Dan Huh, Associate Professor in the Department of Bioengineering at the University of Pennsylvania’s School of Engineering and Applied Science, seeks answers to these questions by replicating biological systems outside of the body. These external copies of internal systems promise to boost drug efficacy while providing new levels of knowledge about patient health.
An innovator of organ-on-a-chip technology, or miniature copies of bodily systems stored in plastic devices no larger than a thumb drive, Huh has broadened his attention to engineering mini-organs in a dish using a patient’s own cells.
The 2022 iGEM team from left to right: June Ahn, Shreya Villimanalan, Adiva Daniar, Wangari Mbuthia, Cristina Perez and Moses Zeidan.
Congratulations to the 2022 University of Pennsylvania iGEM Team who took home a gold medal in the iGEM Grand Jamboree. This international competition of multidisciplinary teams of graduate and undergraduate students presenting original projects in synthetic biology culminated in the in-person Jamboree event held in Paris, France in October 2022. Over 370 judges awarded prizes and medals to the 350+ teams representing over 40 countries.
The 2022 Penn team was awarded a Gold Medal for their project “Photocreate,” a toolbox to control intercellular communication using optogenetics. Their plasmid constructs are designed to control protein secretion, display and shedding using a photocleavable protein, Phocl. The full abstract reads:
Intercellular communication is primarily studied using synthetic protein-level circuits. These circuits currently lack the spatial and temporal control necessary for targeted and time-sensitive applications. To address this gap, we developed Photocrete, a toolbox of protein constructs for light-inducible control of protein display, secretion, and shedding. We expanded upon RELEASE (Vlahos et al.), a modular and generalizable protein circuit which utilizes an ER retention motif and an exogenous protease to control protein secretion. We optogenetically modified RELEASE by replacing different components with the photocleavable protein PhoCl, allowing us to control the mammalian secretion pathway at distinct nodes with finely-tuned light administration regimens. Preliminary results indicate integration of Photocrete into the secretion pathway, but more research is necessary to determine optimal light administration settings. The potential for high spatial and temporal control of Photocrete could allow researchers to perform various signaling studies and develop therapeutics at a new level of precision.
The 2022 iGEM team includes undergraduates June Ahn (B.S. in Biochemistry, Physics and Nutrition), Adiva Daniar (B.S.E. in Bioengineering, minor in Engineering Entrepreneurship), Wangari Mbuthia (B.S.E. in Bioengineering), Cristina Perez (B.S.E. in Bioengineering, minor in Physics), Shreya Vallimanalan (B.S.E. in Bioengineering, minor in Computational Neuroscience), an d Moses Zeidan (B.S.E. in Bioengineering, minor in Chemistry and Spanish). They were mentored by graduate students David Gonzalez-Martinez, Gabrielle Ho, Zikang Huang, and Will Benman. Their faculty advisor is Lukasz Bugaj, Assistant Professor in Bioengineering.
Read the full results of the 2022 iGEM Competition here.
Bella Mirro, a fourth year student in Bioengineering who also minors in Chemistry, spoke with 34th Street Magazine about her many roles at Penn, including being Co–President of Shelter Health Outreach Program (SHOP), a Research Assistant in lab of Michal A. Elovitz, the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health at Penn Medicine, and a Penn Engineering Council Marketing Team Member. In this Q&A, she discusses her research in women’s health and her passions for accessible healthcare, serving Philadelphia’s homeless community, and good food.
Penn Engineering is proud to announce the establishment of the Madison “Maddie” Magee Award for Undergraduate Excellence, named in honor of the memory of Madison “Maddie” N. Magee, who graduated with both a bachelor’s degree in Mechanical Engineering and Applied Mechanics (MEAM) and a master’s degree in Bioengineering (BE) in 2021. Following her time at Penn, Maddie joined the Integrative Baseball Performance department of the Philadelphia Phillies, where she collaborated with a group in developing the next generation of baseball players by analyzing biomechanics data.
In 
Mannickarottu and his team have found that “creativity needs to let go of control – that’s when fun things happen.” As the lab staff and faculty started to allow more creative freedom in the undergraduate bioengineers’ education, the requests for more supplies started pouring in and the lab’s activities and resources grew. “Honestly, we’re driven almost entirely by student requests and student demands,” says Mannickarottu. So when a student requested a sewing machine for a project? They went out and bought one, adding to their ever-growing stockpile of tools. Over time, more and more diverse projects have emerged from the BE Labs, many of them going on to win awards and grow beyond Penn’s campus as independent 
To help others get started, the Penn BE Labs staff have put a wide range of resources 
