LeAnn Dourte’s “Active Learning” Philosophy

LeAnn Dourte, Practice Associate Professor in Bioengineering, has been one of the most active members of the Penn Engineering faculty in pioneering the Structured, Active, In-Class Learning (SAIL) model of education. In a recent issue of the Penn Almanac, Dourte boils down her practical advice for faculty looking to make their courses more interactive and dynamic into one simple philosophy: “Just change 10 minutes.”

“The effectiveness of these 10-minute activities hinges on their alignment with learning objectives. Students are always on the lookout for anything that they see as busy-work, so articulating the purpose of such activities is paramount to their success. These are some of the goals I think about when I design activities with my learning objectives in mind. While some of these approaches are specific to subjects with quantitative problem solving, many have applications across disciplines.”

Dourte’s article articulates her active learning approach, along with a list of specific learning objectives, including encouraging diverse perspectives, promoting error recognition and correction, and more.

Dourte’s contributions to pedagogy were recognized with a 2023 Provost’s Award for Teaching Excllence by Non-Standing Faculty.

Read “Just Change 10 Minutes” in Volume 70, Issue 27 of the Penn Almanac.

Read more stories featuring Dourte in the BE Blog.

Precision Pulmonary Medicine: Penn Engineers Target Lung Disease with Lipid Nanoparticles

by Ian Scheffler

Penn Engineers have developed a way to target lung diseases, including lung cancer, with lipid nanoparticles (LNPs). (wildpixel via Getty Images)

Penn Engineers have developed a new means of targeting the lungs with lipid nanoparticles (LNPs), the miniscule capsules used by the Moderna and Pfizer-BioNTech COVID-19 vaccines to deliver mRNA, opening the door to novel treatments for pulmonary diseases like cystic fibrosis. 

In a paper in Nature Communications, Michael J. Mitchell, Associate Professor in the Department of Bioengineering, demonstrates a new method for efficiently determining which LNPs are likely to bind to the lungs, rather than the liver. “The way the liver is designed,” says Mitchell, “LNPs tend to filter into hepatic cells, and struggle to arrive anywhere else. Being able to target the lungs is potentially life-changing for someone with lung cancer or cystic fibrosis.”

Previous studies have shown that cationic lipids — lipids that are positively charged — are more likely to successfully deliver their contents to lung tissue. “However, the commercial cationic lipids are usually highly positively charged and toxic,” says Lulu Xue, a postdoctoral fellow in the Mitchell Lab and the paper’s first author. Since cell membranes are negatively charged, lipids with too strong a positive charge can literally rip apart target cells.  

Typically, it would require hundreds of mice to individually test the members of a “library” of LNPs — chemical variants with different structures and properties — to find one with a low charge that has a higher likelihood of delivering a medicinal payload to the lungs.

Instead, Xue, Mitchell and their collaborators used what is known as “barcoded DNA” (b-DNA) to tag each LNP with a unique strand of genetic material, so that they could inject a pool of LNPs into just a handful of animal models. Then, once the LNPs had propagated to different organs, the b-DNA could be scanned, like an item at the supermarket, to determine which LNPs wound up in the lungs. 

Read the full story in Penn Engineering Today.

Penn Bioengineering Student Kaitlin Mrksich Named 2024 Goldwater Scholar

by Louisa Shepard

Four University of Pennsylvania undergraduates have received 2024 Goldwater Scholarships, awarded to second- or third-year students planning research careers in mathematics, the natural sciences, or engineering.

Penn’s 2024 Goldwater Scholars are third-years Hayle Kim, Eric Myzelev, and Eric Tao in the College of Arts and Sciences, and Kaitlin Mrksich in the School of Engineering and Applied Science.

They are among the 438 students named 2024 Goldwater Scholars from 1,353 undergraduates students nominated by 446 academic institutions in the United States, according to the Barry Goldwater Scholarship & Excellence in Education Foundation. Each scholarship provides as much as $7,500 each year for as many as two years of undergraduate study.

The students applied for the Goldwater Scholarship with assistance from Penn’s Center for Undergraduate Research and Fellowships. Penn has had 63 Goldwater Scholars named since Congress established the scholarship in 1986 to honor U.S. Senator Barry Goldwater.

Mrksich, from Hinsdale, Illinois, is majoring in bioengineering. She is interested in developing drug delivery systems that can serve as novel therapeutics for a variety of diseases. Mrksich works in the lab of Michael J. Mitchell where she investigates the ionizable lipid component of lipid nanoparticles for mRNA delivery. At Penn, Mrksich is the president of the Biomedical Engineering Society, where she plans community building and professional development events for bioengineering majors. She is a member of the Kite and Key Society, where she organizes virtual programming to introduce prospective students to Penn. She is a member of Tau Beta Pi engineering honor society, and the Sigma Kappa sorority. She also teaches chemistry to high schoolers as a volunteer in the West Philadelphia Tutoring Project through the Civic House. After graduating, Mrksich plans to pursue an M.D./Ph.D. in bioengineering.

Read the full announcement in Penn Today.

Mrksich was awarded a Student Award for Outstanding Research (Undergraduate) by the Society for Biomaterials earlier this year. Read the story in the BE Blog.

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.

“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.

New Chip Opens Door to AI Computing at Light Speed

by Ian Scheffler

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

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

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

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

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

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

Read the full story in Penn Engineering Today.

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

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

by Meagan Raeke

(From left to right) Breakthrough Prize recipients Drew Weissman, Virginia M-Y Lee, Katalin Karikó, and Carl June at a reception on Feb. 13. (Image: Courtesy of Penn Medicine News)

In popular culture, scientific discovery is often portrayed in “Eureka!” moments of sudden realization: a lightbulb moment, coming sometimes by accident. But in real life—and in Penn Medicine’s rich history as a scientific innovator for more than 250 years—scientific breakthroughs can never truly be distilled down to a single, “ah-ha” moment. They’re the result of years of hard work, perseverance, and determination to keep going, despite repeated, often discouraging, barriers and setbacks. 

“Research is [like taking], four, or six, or eight steps back, and then a little stumble forward,” said Drew Weissman, MD, PhD, the Roberts Family Professor of Vaccine Research. “You keep doing that over and over and somehow, rarely, you can get to the top of the step.” 

For Weissman and his research partner, Katalin Karikó, PhD, an adjunct professor of Neurosurgery, that persistence—documented in thousands of news stories across the globe—led to the mRNA technology that enabled two lifesaving COVID-19 vaccines, earning the duo numerous accolades, including the highest scientific honor, the 2023 Nobel Prize in Medicine

Weissman and Karikó were also the 2022 recipients of the Breakthrough Prize in Life Sciences, the world’s largest science awards, popularly known as the “Oscars of Science.” Founded in 2012 by a group of web and tech luminaries including Google co-founder Sergey Brin and Meta CEO Mark Zuckerberg, the Breakthrough Prizes recognize “the world’s top scientists working in the fundamental sciences—the disciplines that ask the biggest questions and find the deepest explanations.” With six total winners, including four from the Perelman School of Medicine (PSOM), Penn stands alongside Harvard and MIT as the institutions whose researchers have been honored with the most Breakthrough Prizes. 

Virginia M.Y. Lee, PhD, the John H. Ware 3rd Professor in Alzheimer’s Research, was awarded the Prize in 2020 for discovering how different forms of misfolded proteins can move from cell to cell and lead to neurodegenerative disease progression. Carl June, MD, the Richard W. Vague Professor in Immunotherapy, is the most recent recipient and will be recognized at a star-studded red-carpet event in April for pioneering the development of CAR T cell therapy, which programs patients’ own immune cells to fight their cancer.

The four PSOM Breakthrough Prize recipients were honored on Tuesday, Feb. 13, 2024, when a new large-scale installation was unveiled in the lobby of the Biomedical Research Building to celebrate each laurate and their life-changing discoveries. During a light-hearted panel discussion, the honorees shared how a clear purpose, dogged determination, and a good sense of humor enabled their momentum forward. 

Read the full story in Penn Medicine News.

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

Weissman presented the Department of Bioengineering’s 2022 Herman P. Schwan Distinguished Lecture: “Nucleoside-modified mRNA-LNP therapeutics.” Read more stories featuring Weissman in the BE Blog here.

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.