“’The students all come here and they hang out and they build stuff,’ said David Issadore, associate professor of bioengineering and electrical and systems engineering. ‘This junior-level course is kind of an entry point for their senior design. So next year, all these students are going to take on new projects, and then they all kind of hang around here and they build incredible stuff.’”
The profile of the BE Labs is part of Technical.ly’s 2023 Universities Month, a series focusing on the latest trends and tech in higher education.
A new Penn Medicine preclinical study demonstrates a simultaneous ‘knockout’ of two inflammatory regulators boosts T cell expansion to attack solid tumors.
by Meagan Raeke
A new approach that delivers a “one-two punch” to help T cells attack solid tumors is the focus of a preclinical study by researchers from the Perelman School of Medicine. The findings, published in the Proceedings of the National Academy of Sciences, show that targeting two regulators that control gene functions related to inflammation led to at least 10 times greater T cell expansion in models, resulting in increased anti-tumor immune activity and durability.
“We want to unlock CAR T cell therapy for patients with solid tumors, which include the most commonly diagnosed cancer types,” says June, the new study’s senior author. “Our study shows that immune inflammatory regulator targeting is worth additional investigation to enhance T cell potency.”
One of the challenges for CAR T cell therapy in solid tumors is a phenomenon known as T cell exhaustion, where the persistent antigen exposure from the solid mass of tumor cells wears out the T cells to the point that they aren’t able to mount an anti-tumor response. Engineering already exhausted T cells from patients for CAR T cell therapy results in a less effective product because the T cells don’t multiply enough or remember their task as well.
Previous observational studies hinted at the inflammatory regulator Regnase-1 as a potential target to indirectly overcome the effects of T cell exhaustion because it can cause hyperinflammation when disrupted in T cells—reviving them to produce an anti-tumor response. The research team, including lead author David Mai, a bioengineering graduate student in the School of Engineering and Applied Science, and co-corresponding author Neil Sheppard, head of the CCI T Cell Engineering Lab, hypothesized that targeting the related, but independent Roquin-1 regulator at the same time could boost responses further.
“Each of these two regulatory genes has been implicated in restricting T cell inflammatory responses, but we found that disrupting them together produced much greater anti-cancer effects than disrupting them individually,” Mai says. “By building on previous research, we are starting to get closer to strategies that seem to be promising in the solid tumor context.”
Dahin Song, a third year undergraduate student in Bioengineering, penned a guest blog post for Penn Career Services as part of their ongoing series of posts by recipients of the 2022 Career Services Summer Funding Grant. In this post, Song talks about her opportunity to conduct research in the SMART Lab of Daeyeon Lee, Professor and Evan C. Thompson Term Chair for Excellence in Teaching in the Department of Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group. During her summer research, Song worked on increasing the stability of the monolayer in microbubbles, gas particles which have been put to therapeutic use. She writes:
“My project was on increasing the stability of the monolayer using cholesterol; theoretically, this would decrease the permeability while maintaining the fluidity of the monolayer. Being given my own project at the get-go was initially intimidating; initial learning curve was overwhelming – along with new wet lab techniques and protocols, I learned a whole new topic well enough to ask meaningful questions. But in retrospect, throwing myself headlong into a project was the best method to immerse me in the research environment, especially as a first-time researcher. I learned how to read papers efficiently, troubleshoot research problems, navigate in a laboratory environment, and be comfortable with working independently but more importantly, with others.”
Fourth year undergraduate Jerry Gao (BE ’23) is the latest student featured in 34th Street Magazine’s “Ego of the Week” series. Jerry, who hails from Coppell, TX, majors in Bioengineering with a minor in Asian American Studies. In addition to his academic studies, he is passionate about education and literacy, working with The Signal, the Asian Pacific American Leadership Initiative, and the Penn Reading Initiative. In this Q&A, he discusses the sense of community that brought him to Penn, the love of cooking (and gifting food to his friends) that powers his @gaos_chows Instagram account, and his experience as a student and now TA in Penn Bioengineering’s “BE MAD” lab class:
“Now that you’re on your way to graduating, what have been your favorite classes or experiences in Bioengineering or Asian American Studies?
‘In terms of bioengineering, there’s definitely a clear favorite that I have. It’s actually the class I’m a TA for right now. It’s “Bioengineering Modeling, Analysis, and Design,” and it’s basically the lab that all junior bioengineers take. There’s one particular lab we do in the class that always catches everyone’s attention; it’s called the cockroach lab. I think it’s one of the biggest reasons why people want to study bioengineering at Penn in particular.
It’s a segue into prosthetics and different medical devices that can help restore people’s limb functions. We order hundreds of cockroaches and then we put them in a little bit of an ice bath to anesthetize. We amputate their legs, which will essentially serve as our prosthetics, and then implant metal electrodes into two different spots of the leg. Then, we go into our computer program and type different lines of code that can help replicate different signal waves to move the legs. If you submit a wave with a particular frequency and particular amplitude, it’ll cause a leg to move in one direction, and if you do a different combination of the amplitude and frequency, it’ll cause it to move in the other direction. The next task is to trace the end of the leg and try to choreograph the leg to spell the letters B and E for bioengineering. It’s so fun to be able to see what combination of leg movements in the servo motor can form the backbone of the B for example, what can form the three lines of the E. I would say that’s probably my favorite moment in the bioengineering department.'”
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.
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.
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.
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.
“[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.
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.
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.