Launching the Next Generation of Faculty Part 4 – Raghav Garg

Authored by Coley Coleman and Thembi Ford

Raghav Garg,
Raghav Garg

On August 1, 2026, Raghav Garg joined Texas A&M University as an Assistant Professor in the Department of Electrical and Computer Engineering, where he is establishing a research program dedicated to implantable and wearable neural interfaces for monitoring and treating neurological diseases.

At College Station, Garg’s laboratory will work at the intersection of bioelectronics innovation, neuroengineering, and clinical neuroscience, developing next-generation neurotechnologies that move from the bench directly into the hands of clinicians and patients. His transition to leading an independent research group builds on the interdisciplinary training and clinical perspective he cultivated during his 4.5 years in the Vitale Lab and at Penn’s Center for Neuroengineering and Therapeutics (CNT).

Garg’s time at Penn was defined by an uncommon proximity to both the science and the human stakes behind it. As a member of the CNT, he operated within a distinctly interdisciplinary environment that brought engineers and neurologists into sustained, meaningful dialogue.

“Being a part of the CNT exposed me to an interdisciplinary environment where I had the rare opportunity of interacting directly with neurologists as well as bioengineers,” says Garg. “Learning about the day-to-day realities of patient care and the limitations of existing clinical neurotechnologies allowed me to identify the most pressing bottlenecks in neurological disease care.”

That immersion in clinical realities proved formative. Rather than pursuing research questions driven purely by engineering novelty, Garg developed a framework for translational problem-solving, asking not only what is technically possible, but what patients and clinicians most urgently need. This philosophy now anchors his independent research agenda at Texas A&M.

Under the mentorship of Dr. Flavia Vitale, Associate Professor in Neurology and Bioengineering, Garg was given the latitude to evolve from a trainee into an independent scientific thinker. That freedom, he explains, was both deliberate and transformative.

Dr. Vitale provided him with substantial research autonomy, allowing him to take full ownership of his projects and develop the confidence and instincts of a principal investigator. She also guided him through the rigorous and often opaque process of grant writing, a skill that yielded immediate results. Garg was awarded a young investigator grant to develop wearable technologies for managing Tourette’s syndrome in pediatric populations, a project that exemplifies the patient-centered focus he carried throughout his postdoctoral training.

Alongside research independence, Dr. Vitale cultivated Garg’s identity as a mentor. He worked with students across every level of training, from high school students through graduate researchers, building the hands-on mentorship experience that has become one of his most valuable assets as he launches his own group at Texas A&M.

“My time at Penn transformed my career,” says Garg. “The mentorship and support I received from Dr. Vitale have been instrumental in preparing me for a faculty role.”

As Garg looks ahead, his ambitions extend beyond individual research milestones. A primary goal is establishing a research program that doesn’t just innovate at the bench, but ensures those innovations reach patients through strong clinical and interdisciplinary partnerships spanning neuroscience, bioengineering, and medicine.

Equally important to Garg is the culture he builds within his own lab. He envisions an environment where scientific rigor and collaborative spirit are inseparable, a space where researchers tackle the hardest problems not in isolation, but together.

“An immediate priority for me is to establish a lab culture that pursues scientific rigor while being deeply rooted in open collaboration,” says Garg. “I want to create an environment where researchers tackle complex challenges together.”

For those hoping to follow a similar path into academic faculty positions, Garg offers hard-won perspective, distilled into a few core principles: Believe in your training, your ideas, and yourself; Lean on a network of peers who can challenge and support you through every stage of the journey; And approach every obstacle, every failed experiment, every rejected grant, as data, not defeat.

“Treat each step as a new experiment,” says Garg. “Yes, you can learn from others’ experiences, but always be learning from ‘successes,’ and more importantly [from] ‘failures.’ The objective is to keep iterating and moving forward.”

As he prepares to step into his new role, Garg takes a moment to look back with gratitude at the community that made it possible.

“I would like to acknowledge all the mentors, collaborators, students, and staff at Penn that I have interacted with over the last 4.5 years,” says Garg. “Each and every one of them has shaped my journey.”

Stepping into his position at Texas A&M, Garg carries with him the clinical grounding, research independence, and collaborative ethos he built at Penn, ready to pass those values on to the next generation of neuroengineers.

Launching the Next Generation of Faculty Part 3 – Hannah Zlotnick

Authored by Coley Coleman and Thembi Ford

Hannah Zlotnick

Following Margaret Billingsley’s move to UVA, the next installment of Launching the Next Generation of Bioengineering Faculty features Hannah Zlotnick (Ph.D. BE 2022), whose doctoral training at Penn laid the foundation for a research career at the intersection of engineering and clinical orthopaedics.

In August 2026, Zlotnick joined Wake Forest University School of Medicine as an Assistant Professor in the Department of Orthopaedic Surgery, where she will establish a laboratory focused on developing materials to model, monitor, and mitigate orthopaedic diseases such as osteoarthritis and joint infection.

At Wake Forest Baptist Hospital, where her laboratory will be physically housed, Zlotnick’s research program will span tissue-on-a-chip platforms, animal models, and injectables for drug delivery and diagnostics. Her move to leading an independent group builds directly on the clinically immersive training she received during her Ph.D. in the Mauck Lab at Penn Bioengineering.

Few graduate training environments blur the line between bench and bedside as deliberately as the Mauck Lab. Physically situated across both the Penn School of Medicine and the Philadelphia VA Hospital, the lab gave Zlotnick something rare: sustained, hands-on exposure to the clinical realities that most early-career engineers encounter only in theory.

Working alongside orthopaedic residents completing their research year in the lab, Zlotnick learned not just the science of musculoskeletal repair, but the practical craft of surgery itself. She learned how to scrub into an operating room, how to close a wound, and how to handle specialized orthopaedic instruments.

“As scientists and engineers, we often work in siloed spaces, designing what we think is the next best thing, but do not consider simple bottlenecks to translation such as how will the surgeon suture this into the body?” says Zlotnick. “While in the Mauck Lab, I was fortunate to train alongside numerous orthopaedic residents who taught me those realities firsthand.”

That immersion translated directly into her Ph.D. research. A significant portion of her doctoral work involved large animal surgeries conducted in collaboration with clinical faculty, including Drs. James Carey and David Steinberg at Penn Medicine, as well as industry partners at Marrow Access Technologies, with the shared goal of advancing the gold standard in cartilage and osteochondral repair.

The throughline of Zlotnick’s career is a commitment to research that is not only scientifically rigorous, but genuinely useful in the clinic. That orientation was shaped across three exceptional laboratory environments: the Grodzinsky Lab at MIT, the Mauck Lab at Penn, and the Burdick Lab at the University of Colorado Boulder.

Each experience deepened her appreciation for what it means to produce work that matters, and each contributed to the scientific and cultural sensibility she now brings to her own group.

“Your lab environment makes a huge impact on your undergraduate, Ph.D., and postdoc research career,” says Zlotnick. “I have been lucky to have been a part of three tremendous laboratories. Each of these groups has produced excellent science while keeping things fun in and out of the lab. I have learned so much from each of these environments and look forward to shaping the culture of my own laboratory.”

Her postdoctoral training also benefited from the support of the Schmidt Science Fellows program, a prestigious fellowship that funded the first half of her postdoctoral research and provided leadership development and mentorship that she credits as a meaningful part of her formation as a scientist and future faculty member.

As Zlotnick establishes her presence at Wake Forest, her immediate priorities reflect both the practical and the philosophical dimensions of launching a new research group. On the practical side, she has already hired a laboratory technician and is actively recruiting undergraduate students and a postdoctoral researcher, with plans to bring on a PhD student in the next hiring cycle.

Alongside building her team, she is navigating the early-career grant landscape and establishing her lab space, two undertakings that demand equal parts strategy and patience. She is also investing time in conversations with faculty colleagues to explore potential collaborations and new project directions.

What ties these efforts together is intentionality. Zlotnick is not simply filling seats; she is assembling a community. “I am first interested in intentionally building our team of curious and creative scientists who are interested in clinically impactful research,” says Zlotnick. “There are lots of things to balance in the early stages of starting a laboratory.”

For researchers considering an academic faculty path, Zlotnick offers pragmatic and personal counsel. Seek out people who are just a step or two ahead of where you are, she advises, and gather perspectives broadly, because policies and norms vary widely across universities, departments, and countries. By collecting diverse input, aspiring faculty can filter for what actually applies to their own situation.

And when it comes to the faculty search itself, she encourages candidates to think beyond the CV.

“Throughout the faculty application process, reflect on both your research plan and your life plan,” says Zlotnick. “Apply to places that will enable you to be successful and happy in both your research and life.”

As Zlotnick steps into her faculty role, she looks back with appreciation at the many people who have carried her forward, including her family,  mentors, and also, lab mates who showed up as supporters, motivators, and friends at every stage of her journey.

“I would like to thank my lab mates for their continuous support throughout my career in academia,” says Zlotnick.

Grounded in clinical purpose and energized by the culture she has both absorbed and helped to create, Zlotnick arrives at Wake Forest University School of Medicine ready to build something new while honoring everything that brought her there.

Launching the Next Generation of Bioengineering Faculty – Part 2: Margaret Billingsley

Authored by Coley Coleman and Thembi Ford

Following Marshall Padilla’s move to Stanford, the next installment of Launching the Next Generation of Bioengineering Faculty features Margaret Billingsley. 

On Aug. 31, 2026, Billingsley will join the University of Virginia as an Assistant Professor of Biomedical Engineering with an appointment in the university’s NanoSTAR Institute, where she will establish a laboratory focused on engineering nanoparticle platforms to treat sex-specific diseases, including ovarian cancer.

In Charlottesville, Billingsley’s research group will operate at the intersection of biomaterials, drug delivery and immunology, developing targeted therapies while advancing new treatment strategies for diseases with significant unmet clinical needs. Her transition to leading an independent laboratory builds on the hands-on research experience and collaborative approach she developed during her time in the Mitchell Lab and at Penn Engineering.

Billingsley’s passion for academic research began as an undergraduate in Dr. Emily Day’s group at the University of Delaware, where she first encountered Ph.D. pathways and faculty careers. At the time, however, running her own laboratory felt like a distant aspiration rather than a tangible next step.

Her perspective transformed when she arrived at Penn as part of the initial graduate student cohort in the Mitchell Lab.

Under the direction of Michael J. Mitchell, Hibbert Professor in Bioengineering, the group develops advanced biomaterials for targeted drug delivery, with major focus areas in lipid nanoparticles and cellular therapies. Joining the lab at its inception gave Billingsley an insider’s view of what it takes to build a research group from the ground up.

“Especially as a member of the first grad student cohort in the Mitchell Lab, I got to see what it takes to grow a new community, jumpstart projects, and navigate the ups-and-downs that come with it,” says Billingsley. “My time in the Mitchell Lab really gave me a playbook for how to approach this next adventure.”

Penn’s clinically oriented environment reinforced the importance of orienting basic science toward tangible patient outcomes, a principle that continues to drive her work in drug delivery.

As Billingsley turns her attention to UVA, her initial focus centers on recruiting a dedicated group of researchers who share a vision for translational biomaterials and effective scientific communication. She also plans to forge connections between UVA’s engineering departments and clinical units to accelerate collaborative projects.

Her approach to mentorship reflects the guidance she received throughout her graduate training. When navigating the academic job market, she relied heavily on Mitchell’s steady support during every phase of application reviews and interview preparation.

“It can be hard to find mentors that will support you across career phases, so I feel incredibly lucky to have no doubts that Mike will be a mentor for life,” says Billingsley. “Even as I transition into this next role and begin building my own research program, it’s still an honor to be a part of the ever-growing Mitchell Lab community.”

Billingsley credits her progress to a wide network of peers, research partners, and mentors across Penn who challenged her scientifically and offered continuous encouragement.

Stepping into her role at UVA offers Billingsley the opportunity to establish her own scientific hub, bringing together the clinical focus, collaborative spirit, and mentorship culture that shaped her journey in Penn Bioengineering.

Launching the Next Generation of Bioengineering Faculty – Part 1: Marshall Padilla

Marshall Padilla

The first story in “Launching the Next Generation of Bioengineering Faculty” highlights how the Department of Bioengineering and the Mitchell Lab helped prepare Padilla to launch an interdisciplinary research program of his own.

Bioengineering advances through people who can move across disciplines, build new tools and train the next generation of scientists to ask questions that do not fit neatly inside one field.

This summer, the Department of Bioengineering at the University of Pennsylvania is highlighting members of its community who are beginning faculty careers at institutions across the country and around the world. The series, “Launching the Next Generation of Bioengineering Faculty,” begins with Marshall Padilla, a member of the Mitchell Lab whose next chapter will take him to Stanford University.

On Sept. 1, 2026, Padilla will join Stanford as an Assistant Professor in the Department of Materials Science and Engineering and as an Institute Scholar in Sarafan ChEM-H, an interdisciplinary institute focused on research at the intersection of chemistry, engineering and medicine.

At Stanford, Padilla will launch a lab focused on data-driven nanotechnology for drug delivery, with a particular emphasis on designing the next generation of RNA nanomedicines.

“Essentially, writing the rulebooks for how to design next-generation RNA nanomedicines,” says Padilla.

His future lab will bring together chemical synthesis, biophysical and analytical instrumentation, molecular and cellular biology and animal models. That breadth reflects both the complexity of the problems Padilla plans to study and the training environment that helped shape his approach at Penn Engineering.

RNA medicines, including some vaccines and emerging therapies, depend on delivery systems that can protect genetic instructions, move them through the body and help them reach the right cells. Lipid nanoparticles (LNPs), tiny delivery vehicles made from fat-like molecules, are one of the most important tools for that work.

In the Mitchell Lab, Padilla studied how these systems function at multiple scales, from their chemical makeup to their behavior in living models. That interdisciplinary training, he says, now anchors the research program he plans to build at Stanford.

“My time in Mike Mitchell’s lab was foundational in nearly every dimension,” says Padilla. “Scientifically, it’s where I learned to integrate chemical synthesis with the biophysics and in vivo models needed to understand why RNA lipid nanoparticles work, not just whether it does, which is the approach that now anchors my research program.”

Led by Michael J. Mitchell, Professor in Bioengineering in Penn Engineering, the Mitchell Lab develops new biomaterials and drug delivery technologies, with a particular focus on lipid nanoparticles and RNA therapeutics. For Padilla, the lab offered more than technical preparation. It also provided opportunities to lead independent and collaborative projects across Penn centers and institutes, industry partners and national labs, while mentoring graduate and undergraduate students.

That combination of scientific range and mentorship experience helped prepare him for the transition from trainee to faculty member.

“The breadth of Penn’s ecosystem, from the RNA Innovation community to clinical collaborators, also taught me how much faster science moves when it’s interdisciplinary,” says Padilla.

As Padilla prepares to launch his own research group, he says his first priority is people.

At Stanford, he plans to recruit and mentor a founding group of students and postdoctoral fellows while establishing a lab culture that supports both rigorous science and the people doing it. Scientifically, he aims to build the core platforms his group will need, including synthesis and biophysical characterization pipelines, while developing collaborations across Stanford’s Materials Science and Engineering department, Sarafan ChEM-H and the university’s broader medical, engineering and chemistry communities.

Padilla credits the Mitchell Lab with helping him understand how to build that kind of environment.

“Mike [Mitchell] modeled how to run a rigorous, ambitious, and genuinely supportive research group, and that’s the environment I want to build at Stanford,” says Padilla.

That lesson is central to what he hopes to carry forward. His research group will be built around diverse scientific backgrounds, reflecting the many kinds of expertise needed to improve drug delivery and RNA nanomedicine.

Padilla also points to a wider network of mentors and collaborators who helped shape his path to the professoriate.

He credits Mitchell for creating a lab where he could grow into an independent scientist and the members of the Mitchell Lab for supporting him throughout his training. He also notes the support of Anh Le and the Center for Innovation and Precision Dentistry, which supported him through an NIH T90 Fellowship, as well as Kushol Gupta at the University of Pennsylvania Johnson Foundation Structural Biology and Biophysics Core, whose work with Padilla helped make biophysical applications a central part of his future lab.

“It takes dozens of motivated people to prepare one professor,” says Padilla.

The path to his faculty role was not quick. Padilla began applying for faculty positions in 2024 and, after nearly two years and more than 120 applications, received the opportunity he had been working toward.

“I got my dream job,” he says. “It was a very difficult process with many failures, but having that support network is crucial for staying positive and constantly approving the application material.”

For Padilla, the next step is not only a new title or a new institution. It is a chance to build a research community of his own, one shaped by the science, mentorship and collaboration that defined his time in the Department of Bioengineering.

Developing Kidneys from Scratch: Alex Hughes Tackles the Tremendous Burden of Kidney Disease

by Ian Scheffler

Alex Hughes, Assistant Professor in Bioengineering, holds a model of a developing kidney. (Credit: Bella Ciervo)

To Alex Hughes, Assistant Professor in Bioengineering within Penn Engineering and in Cell and Developmental Biology within Penn Medicine, the kidney is a work of art. “I find the development of the kidney to be a really beautiful process,” says Hughes.

Most people only ever see the organ in cross-section, through textbooks or by dissecting animal kidneys in high school biology class: a bean-shaped slice with lots of tiny tubes. “I think that really undersells how amazing the structure is,” says Hughes, who points out that kidneys grow in utero like forests of pipes, branching exponentially.

Densely packed with tubules clustered in units known as nephrons, kidneys cleanse the blood, maintaining the body’s fluid and electrolyte balance, while also regulating blood pressure. The organ played a crucial role in vertebrates emerging from the ocean: as one paper puts it, kidneys preserve the primordial ocean in all of us.

Unfortunately, kidneys struggle in the modern world. Excessively salty food, being overweight, not exercising enough, drinking too much and smoking can all raise blood pressure, which damages the kidney’s tiny blood vessels, as does diabetes.

In some cases, damage to the kidney’s nephrons can be slowed with lifestyle changes, but, unlike the liver, bones and skin, which can regrow damaged tissue, kidneys have a limited capacity to regenerate. At present, without a transplant, the nephrons we have at birth must last a lifetime.

Read the full story in Penn Engineering Today.

Understanding the Cellular Mechanisms Driving Solid Tumors’ Robust Defense System

by Nathi Magubane

In a collaborative interdisciplinary study, Michael Mitchell of the School of Engineering and Applied Science, Wei Guo of the School of Arts & Sciences, and Drew Weissman of the Perelman School of Medicine show that solid tumors can block drug-delivery mechanisms with a “forcefield-like” effect but certain genetic elements that can effectively “shut down” the forcefield. Their findings hint at new targets for delivering cancer treatments that use the body’s immune system to fight tumors. (Image: iStock / CIPhotos)

The tumor microenvironment—an ad hoc, messy amalgamation of signaling molecules, immune cells, fibroblasts, blood vessels, and the extracellular matrix—acts like a “powerful security system that protects solid tumors from invaders seeking to destroy them,” says Michael Mitchell, a bioengineer at the University of Pennsylvania working on nanoscale therapeutics aimed at targeting cancers.

“A lot like the Death Star with its surrounding fleet of fighter ships and protective shields, solid tumors can use features like immune cells and vasculature to exert force, acting as a physical barrier to rebel forces (nanoparticles) coming in to deliver the payload that destroys it,” Mitchell says.

Now, researchers in the Mitchell lab have teamed up with Wei Guo’s group in the School of Arts & Sciences at Penn and Drew Weissman of the Perelman School of Medicine to figure out the molecular mechanisms that make tumor microenvironments seemingly impenetrable and found that small extracellular vesicles (sEVs) are secreted by tumor cells and act as a “forcefield,” blocking therapeutics. Their findings are published in Nature Materials.

“This discovery reveals how tumors create a robust defense system, making it challenging for nanoparticle-based therapies to reach and effectively target cancer cells,” Guo says. “By understanding the cellular mechanisms driving these responses, we can potentially develop strategies to disable this defense, allowing therapeutics to penetrate and attack the tumor more efficiently.”

The research builds on a prior collaboration between Guo and Mitchell’s labs, wherein the teams focused on how tumor-associated immune cells, known as macrophages, contribute to the suppression of anti-tumor immunity by secreting extracellular vesicles.

Read the full story in Penn Today.

Michael Mitchell is an associate professor in the Department of Bioengineering in the School of Engineering and Applied Science and director of the Lipid Nanoparticle Synthesis Core at the Penn Institute for RNA Innovation at the University of Pennsylvania.

Wei Guo is the Hirsch Family President’s Distinguished Professor in the Department of Biology in Penn’s School of Arts & Sciences.

Ningqiang Gong, a former postdoctoral researcher in the Mitchell lab at Penn Engineering, is an assistant professor at the University of Science and Technology of China.

Wenqun Zhong is a reseearch associate in the Guo Laboratory in Penn Arts & Sciences.

Other authors include: Alex G Hamilton, Dongyoon Kim, Junchao Xu, and Lulu Xue of Penn Engineering; Junhyong Kim, Zhiyuan Qin, and Fengyuan Xu of Penn Arts & Sciences; Mohamad-Gabriel Alameh and Drew Weissman of the Perelman School of Medicine; Andrew E. Vaughn and Gan Zhao of the Penn School of Veterinary Medicine; Jinghong Li and Xucong Teng of the University of Beijing; and Xing-Jie Liang of the Chinese Academy of Sciences.

This research received support from the U.S. National Institutes of Health (DP2 TR002776, R35 GM141832, and NCI P50 CA261608), Burroughs Wellcome Fund, U.S. National Science Foundation CAREER Award (CBET-2145491), and an American Cancer Society Research Scholar Grant (RGS-22-1122-01-ET.)

Measuring Chaos: Using Machine Learning to Satisfy Our Need to Know

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How do we measure chaos and why would we want to? Together, Penn engineers Dani S. Bassett, J. Peter Skirkanich Professor in Bioengineering and in Electrical and Systems Engineering, and postdoctoral researcher Kieran Murphy leverage the power of machine learning to better understand chaotic systems, opening doors for new information analyses in both theoretical modeling and real-world scenarios.

Humans have been trying to understand and predict chaotic systems such as weather patterns, the movement of planets and population ecology for thousands of years. While our models have continued to improve over time, there will always remain a barrier to perfect prediction. That’s because these systems are inherently chaotic. Not in the sense that blue skies and sunshine can turn into thunderstorms and torrential downpours in a second, although that does happen, but in the sense that mathematically, weather patterns and other chaotic systems are governed by physics with nonlinear characteristics. 

“This nonlinearity is fundamental to chaotic systems,” says Murphy. “Unlike linear systems, where the information you start with to predict what will happen at timepoints in the future stays consistent over time, information in nonlinear systems can be both lost and generated through time.”

Like a game of telephone where information from the original source gets lost as it travels from person to person while new words and phrases are added to fill in the blanks, outcomes in chaotic systems become harder to predict as time passes. This information decay thwarts our best efforts to accurately forecast the weather more than a few days out.

“You could put millions of probes in the atmosphere to measure wind speed, temperature and precipitation, but you cannot measure every single atom in the system,” says Murphy. “You must have some amount of uncertainty, which will then grow, and grow quickly. So while a prediction for the weather in a few hours might be fairly accurate, that growth in uncertainty over time makes it impossible to predict the weather a month from now.”

In their recent paper published in Physical Review Letters, Murphy and Bassett applied machine learning to classic models of chaos, physicists’ reproductions of chaotic systems that do not contain any external noise or modeling imperfections, to design a near-perfect measurement of chaotic systems to one day improve our understanding of systems including weather patterns. 

“These controlled systems are testbeds for our experiments,” says Murphy. “They allow us to compare with theoretical predictions and carefully evaluate our method before moving to real-world systems where things are messy and much less is known. Eventually, our goal is to make ‘information maps’ of real-world systems, indicating where information is created and identifying what pieces of information in a sea of seemingly random data are important.” 

Read the full story in Penn Engineering Today.

Penn Pioneers a ‘One-Pot Platform’ to Promptly Produce mRNA Delivery Particles

by Nathi Magubane

Lipid nanoparticles present one of the most advanced drug delivery platforms to shuttle promising therapeutics such as mRNA but are limited by the time it takes to synthesize cationic lipids, a key component. Now, Michael Mitchell and his team at the School of Engineering and Applied Science have developed a faster way to make cationic lipids that are also more versatile, able to carry different kinds of treatments to target specific organs. (Image: iStock / Dr_Microbe)

Imagine a scenario where a skilled hacker must upload critical software to update a central server and thwart a potentially lethal virus from wreaking havoc across a vast computer network. The programmer, armed with the lifesaving code, must navigate through treacherous territory teeming with adversaries, and success hinges on promptly getting a safe, stealthy delivery vehicle that can place the hacker exactly where they need to be.

In the context of modern medicine, messenger RNA (mRNA) serves as the hacker, carrying genetic instructions to produce specific proteins within cells that can induce desired immune responses or sequester maladaptive cellular elements. Lipid nanoparticles (LNPs) are the stealthy delivery vehicles that transport these fragile mRNA molecules through the bloodstream to their target cells, overcoming the body’s defenses to deliver their payload safely and efficiently.

However, much like building an advanced stealth vehicle, the synthesis of cationic lipids—a type of lipid molecule that’s positively charged and a key component of LNPs—is often a time-consuming process, involving multiple steps of chemical synthesis and purification.

Now, Michael Mitchell and a team at the University of Pennsylvania have addressed this challenge with a novel approach that leverages a compound library fabrication technique known as “click-like chemistry” to create LNPs in a single, simple step. Their findings, published in the journal Nature Chemistry, show that this method not only speeds up the synthesis process but also presents a way to equip these delivery vehicles with a “GPS” to better target specific organs such as the liver, lungs, and spleen, potentially opening new avenues for treating a range of diseases that arise in these organs.

“We’ve developed what we call an amidine-incorporated degradable (AID) lipid, a uniquely structured biodegradable molecule,” Mitchell says. “Think of it as an easy-to-build custom mRNA vehicle with a body kit that informs its navigation system. By adjusting its shape and degradability, we can enhance mRNA delivery into cells in a safe manner. By adjusting the amount of the AID lipid that we incorporate into the LNP, we can also guide it to different organs in the body, much like programming different destinations into a GPS.”

First author Xuexiang Han, a former postdoctoral researcher in the Mitchell Lab, explains that their new approach allows the rapid creation of diverse lipid structures in just an hour, compared to the weekslong process traditionally required.

Read more in Penn Today.

Looking to AI to Solve Antibiotic Resistance

by Nathi Magubane

Cesar de la Fuente (left), Fangping Wan (center), and Marcelo der Torossian Torres (right). Fangping holds a 3D model of a unique ATP synthase fragment, identified by their lab’s deep learning model, APEX, as having potent antibiotic properties.

“Make sure you finish your antibiotics course, even if you start feeling better’ is a medical mantra many hear but ignore,” says Cesar de la Fuente of the University of Pennsylvania.

He explains that this phrase is, however, crucial as noncompliance could hamper the efficacy of a key 20th century discovery, antibiotics. “And in recent decades, this has led to the rise of drug-resistant bacteria, a growing global health crisis causing approximately 4.95 million deaths per year and threatens to make even common infections deadly,” he says.

De la Fuente, a Presidential Assistant Professor, and a team of interdisciplinary researchers have been working on biomedical innovations tackling this looming threat. In a new study, published in Nature Biomedical Engineering, they developed an artificial intelligence tool to mine the vast and largely unexplored biological data—more than 10 million molecules of both modern and extinct organisms— to discover new candidates for antibiotics.

“With traditional methods, it takes around six years to develop new preclinical drug candidates to treat infections and the process is incredibly painstaking and expensive,” de la Fuente says. “Our deep learning approach can dramatically reduce that time, driving down costs as we identified thousands of candidates in just a few hours, and many of them have preclinical potential, as tested in our animal models, signaling a new era in antibiotic discovery.” César de la Fuente holds a 3D model of a unique ATP synthase fragment, identified by his lab’s deep learning model, APEX, as having potent antibiotic properties. This molecular structure, resurrected from ancient genetic data, represents a promising lead in the fight against antibiotic-resistant bacteria.

These latest findings build on methods de la Fuente has been working on since his arrival at Penn in 2019. The team asked a fundamental question: Can machines be used to accelerate antibiotic discovery by mining the world’s biological information? He explains that this idea is based on the notion that biology, at its most basic level, is an information source, which could theoretically be explored with AI to find new useful molecules.

Read the full story in Penn Today.

The CiPD Partners with the Mack Institute for Innovation and Management to Develop Tooth-Brushing Robots

by Melissa Pappas

Left to right: Hong-Huy Tran, Chrissie Jaruchotiratanasakul, Manali Mahajan (Photo Courtesy of CiPD)

The Center for Innovation and Precision Dentistry (CiPD), a collaboration between Penn Engineering and Penn Dental Medicine, has partnered with Wharton’s Mack Institute for Innovation Management on a research project which brings robotics to healthcare. More specifically, this project will explore potential uses of nanorobot technology for oral health care. The interdisciplinary partnership brings together three students from different Penn programs to study the commercialization of a new technology that detects and removes harmful dental plaque.

“Our main goal is to bring together dental medicine and engineering for out-of-the-box solutions to address unresolved problems we face in oral health care,” says Hyun (Michel) Koo, Co-Founding Director of CiPD and Professor of Orthodontics. “We are focused on affordable solutions and truly disruptive technologies, which at the same time are feasible and translatable.”

Read the full story in Penn Engineering Today.

Michel Koo is a member of the Penn Bioengineering Graduate Group. Read more stories featuring Koo in the BE Blog.

To learn more about this interdisciplinary research, please visit CiPD.

This press release has been adapted from the original published by the Mack Institute for Innovation Management.