Cosette Tomita, a master’s student in Bioengineering, spoke with Penn Engineering Graduate Admissions about her research in cellular therapy and her path to Penn Engineering.
“What were you doing before you came to Penn Engineering?
After college I wanted to get some industry experience before going to graduate school, so I spent a year working for a pharmaceutical company in New Jersey. I learned a lot—but mostly I learned that I wanted to go back into academia. So I was looking for a more research-oriented position to boost my graduate school applications, and I found a position at Penn’s cyclotron facility. Shortly after that, I applied to the master’s program. I’m still working at the cyclotron, so I’m doing the program part time.
How has your experience in the program been so far?
I love the research I’m doing here. I love the collaboration we have and the fact that I’m able to work with whoever I want to. And I can only say good things about my PI, Robert Mach. He’s a very busy man, but he makes time for his people. And he recognizes when somebody has a lot on their plate and he will go to bat for that person.
What’s your research all about?
The focus of my PI’s lab is on neurodegenerative diseases and opiate use, so we’re looking to make imaging agents and antagonists that can help with the opioid crisis.
For my project, I wanted to look at treating neurodegenerative disease from the perspective of cellular therapy. My PI doesn’t have that expertise, so when I came to him with this idea, he said I should talk to Mark Sellmyer in the bioengineering department. He does a lot of cellular therapies, cell engineering, protein engineering and things of that nature. So his lab is more biological.
I don’t have a grant for my research, so my advisors are supporting it out of their own pockets. They could have said, no, you need to work on this project that’s already going on in the lab. But they gave me the intellectual freedom to do what I wanted to do.”
Ongoing clinical trials have demonstrated that psychedelics like psilocybin and LSD can have rapid and long-lived antidepressant and anti-anxiety effects. A related clinical problem is chronic pain, which is notoriously difficult to treat and often associated with depression and anxiety.
This summer, Ahmad Hammo, a rising third-year student in bioengineering in the School of Engineering and Applied Science, is conducting a pilot study to explore psilocybin’s potential as a therapy for chronic pain and the depression that often accompanies it.
“There’s a strong correlation between chronic pain and depression, so I’m looking at how a psychedelic might be used for treating both of these things simultaneously,” says Hammo, who is originally from Amman, Jordan.
Hammo’s project focuses on neuropathic pain, pain associated with nerve damage. Like other forms of chronic pain, most experts believe that chronic neuropathic pain is stored in the brain.
“Neuropathic pain can lead to a centralized pain syndrome where the pain is still being processed in the brain,” Cichon says. “It’s as if there’s a loop that keeps playing over and over again, and this chronic form is completely divorced from that initial injury.”
A research team led by engineers at the University of Pennsylvania and Northwestern University scientists has created a new synthetic biology approach, or a “QR code for cancer cells,” to follow tumor cells over time, finding there are meaningful differences in why a cancer cell dies or survives in response to anti-cancer therapies.
Remarkably, what fate cancer cells choose after months of therapy is “entirely predictable” based on seemingly small, yet important, differences that appear even before treatment begins. The researchers also discovered the reason is not genetics, contrary to beliefs held in the field.
The study outlined the team’s new technology platform that developed a QR code for each of the millions of cells for scientists to find and use later — much like tagging swans in a pond. The QR code directs researchers to a genome-wide molecular makeup of these cells and provides information about how they’ve reacted to cancer treatment.
“We think this work stands to really change how we think about therapy resistance,” said Arjun Raj, co-senior author and Professor in Bioengineering in the School of Engineering and Applied Science at the University of Pennsylvania. “Rather than drug-resistant cells coming in just one flavor, we show that even in highly controlled conditions, different ‘flavors’ can emerge, raising the possibility that each of these flavors may need to be treated individually.”
In the study, the lab and collaborators sought to apply synthetic biology tools to answer a key question in cancer research: What makes certain tumors come back a few months or years after therapy? In other words, could the lab understand what causes some rare cells to develop therapeutic resistance to a drug?
“There are many ways cells become different from each other,” said Yogesh Goyal, the co-senior author at Northwestern University. “Our lab asks, how do individual cells make decisions? Understanding this in the context of cancer is all the more exciting because there’s a clinically relevant dichotomy: A cell dies or becomes resistant when faced with therapies.”
Using the interdisciplinary team, the scientists put the before-and-after cloned cells through a whole genome sequencing pipeline to compare the populations and found no systematic underlying genetic mutations to investigate the hypothesis. Raj and Goyal helped develop the QR code framework, FateMap, that could identify each unique cell that seemed to develop resistance to drug therapy. “Fate” refers to whether a cell dies or survives (and if so, how), and the scientists “map” the cells across their lifespan, prior to and following anti-cancer therapy. FateMap is the result of work from several research institutions, and it applies an amalgamation of concepts spanning several disciplines, including synthetic biology, genome engineering, bioinformatics, machine learning and thermodynamics.
“Some are different by chance — just as not all leaves on a tree look the same — but we wanted to determine if that matters,” Goyal said. “The cell biology field has a hard time defining if differences have meaning.”
Artificial intelligence is a new addition to the infectious disease researcher’s toolbox. Yet in merely half a decade, AI has accelerated progress on some of the most urgent issues in medical science and public health. Researchers in this field blend knowledge of life sciences with skill in computation, chemistry and design, satisfying decades-long appeals for interdisciplinary tactics to treat these disorders and stop their spread.
Diseases are “infectious” when they are caused by organisms, including parasites, viruses, bacteria and fungi. People and animals can contract infectious diseases from their environments or food, or through interactions with one another. Some, but not all, are contagious.
Infectious diseases are an intractable global challenge, posing problems that continue to grow in severity even as science has offered a steady pace of solutions. The world continues to become more interconnected, bringing people into new kinds and levels of relation, and the climate crisis is throwing environmental and ecological networks out of balance. Diseases that were once treatable by drugs have become resistant, and new drug discovery is more costly than ever. Uneven resource distribution means that certain parts of the world are perennial hotspots for diseases that others never fear.
In the paper, de la Fuente and co-authors assess the progress, limitations and promise of research in AI and infectious diseases in three major areas of inquiry: anti-infective drug discovery, infection biology, and diagnostics for infectious diseases.
Bioengineering researchers at Children’s Hospital of Philadelphia are developing a less invasive and quicker method to create cartilage implants as an alternative to the current treatment for severe subglottic stenosis, which occurs in 10 percent of premature infants in the U.S.
Subglottic stenosis is a narrowing of the airway, in response to intubation. Severe cases require laryngotracheal reconstruction that involves grafting cartilage from the rib cage with an invasive surgery. With grant support from the National Institutes of Health, Riccardo Gottardi, PhD, who leads the Bioengineering and Biomaterials (Bio2) Lab at CHOP, is refining a technology called Meniscal Decellularized scaffold (MEND). Working with a porcine model meniscus, the researchers remove blood vessels and elastin fibers to create pathways that allow for recellularization. Dr. Gottardi and his team then harvest ear cartilage progenitor cells (CPCs) with a minimally invasive biopsy, combine them with MEND, and create cartilage implants that could be a substitute for the standard laryngotracheal reconstruction.
While laryngotracheal reconstruction in the adult population has a success rate of up to 96%, success rates in children range from 75% to 85%, and children often require revision surgery due to a high incidence of restenosis. The procedure also involves major surgery to remove cartilage from the rib cage, which is more difficult for childrens’ smaller bodies.
“Luckily not many children suffer from severe subglottic stenosis, but for those who do, it is really serious,” said Dr. Gottardi, who also is assistant professor in the Department of Pediatrics and Department of Bioengineering at CHOP and the University of Pennsylvania. “With our procedure, we have an easily accessible source for the cartilage and the cells, providing a straightforward and noninvasive treatment option with much potential.”
Riccardo Gottardi is an Assistant Professor in the Department of Pediatrics, Division of Pulmonary Medicine in the Perelman School of Medicine and in the Department of Bioengineering in the School of Engineering and Applied Science. He also holds an appointment in the Children’s Hospital of Philadelphia (CHOP).
Paul Gehret is a Ph.D. student in Bioengineering, an Ashton Fellow and a NSF Fellow. His research focuses on leveraging decellularized cartilage scaffolds and novel cell sources to reconstruct the pediatric airway.
“During my training, I saw that there was overlap where I could do clinical work and science at the same time, and so that’s what I’ve been doing ever since,” Vining says. “As far back as middle school, I always wanted to be a biomedical engineer, and then the clinical side became interesting to me because I didn’t want to only do the theoretical or research side of things. I also wanted the hands-on, practical interaction of a skilled profession.”
The benefits of a dual career: Variety and opportunities to give back
Vining finds that wearing two hats offers the best of both worlds: opportunities to help both individual patients and to contribute to scientific and clinical progress.
“On the dentistry side, what I enjoy is getting to see patients, solving clinical problems, and trying to perform the best treatment I can; it has this rapid pace, which is kind of exciting and keeps you motivated,” Vining says. “And then research allows me to explore my interests and think about making an impact more broadly, not just in dentistry, but in medicine or in the world in general.”
Vining says dental school was demanding, yet a good time to explore his varied interests. He says he’d encourage others to pursue dentistry with an interdisciplinary approach. “Having exposure to different fields or different knowledge while you’re a student is really good for students and the profession in general,” he says.
The path towards a dual career
Vining first delved into research as a biomedical engineering undergraduate at Northwestern University. “I had the opportunity to work in a materials science lab studying the chemistry of surfaces. We would use molecules to modify the properties and surfaces that environments or cells could interact with,” he says.
Then, as a student at the University of Minnesota School of Dentistry, Vining realized that this same materials science research had many applications in dentistry. While in dental school, Vining conducted independent research in a materials science lab and also took the opportunity to do a yearlong fellowship in a cell and developmental biology lab at the National Institutes of Health.
Vining credits this fellowship with launching him towards a Ph.D., which he completed in bioengineering at Harvard in 2020. After earning his Ph.D., Vining conducted research at the Dana-Farber Cancer Institute prior to joining Penn.
Using biomaterials to understand how cells and tissues interact
Vining’s research at Penn aims to understand how the biophysical properties of materials impact cellular processes such as inflammation and fibrosis.
“Fibrosis is a physical change in tissues that produces a scar-like matrix that can inhibit healing, impair cancer treatment, and in general is not compatible with tissues regeneration,” Vining says. “There’s been a lot of effort on antifibrotic drugs, but we’re trying to look at fibrosis a little bit differently. Instead of directly inhibiting fibrosis, we’re trying to understand its consequences for the immune system because the immune system can be hijacked and become detrimental for your tissues.”
Through a better understanding the feedback loop between fibrotic tissue and the immune system, Vining hopes to design interventions to facilitate wound healing and tissue remodeling during restorative dental procedures and for treating diseases including head and neck cancer.
He’s also investigating how biomaterials like the resin used in tooth fillings interact with dental tissues. “Dental fillings rely on decades-old technologies that have been grandfathered in and contain toxic monomers that are not safe for biological systems,” Vining says. “We found a biocompatible resin chemistry that supports cells in vitro, and we’re trying to apply this to new types of dental fillings that promote repair or generation of dental tissues.”
Fostering interdisciplinary collaborations at Penn
“Dr. Vining is an ideal fit for the vision and mission of the CiPD,” says Penn Dental’s Hyun (Michel) Koo, co-founder and co-director of the CiPD. “With a secondary appointment in the School of Engineering, he will be instrumental in continuing to strengthen our engineering collaborations and teaching our students to work across disciplines to advance research, training, and entrepreneurship in this realm.”
Ultimately, Vining says it was Penn’s scientific community and the opportunities for interdisciplinary collaborations that drew him here.
“It was very apparent that there were a lot of potential research paths to pursue here and a lot of opportunities for collaborations,” Vining says. “One of the most exciting things for me so far has been meeting with faculty, whether it’s at Penn Medicine, the School of Engineering, Wharton, Penn Dental, or the Veterinary School. These meetings have already opened up new projects and collaborations.”
The collaboration sparked when Vining saw Mitchell present on a new technology that uses lipid nanoparticles to bind and target bone marrow cells at the 2022 CiPD first annual symposium. “It got me thinking because the dentin inside of teeth is a mineralized tissue very similar to bone, and the pulp inside the dentin is analogous to bone marrow tissue,” Vining says.
Congratulations to the fourteen Bioengineering students to receive 2023 National Science Foundation Graduate Research Fellowship Program (NSF GRFP) fellowships. The prestigious NSF GRFP program recognizes and supports outstanding graduate students in NSF-supported fields. The recipients honorees were selected from a highly-competitive, nationwide pool. Further information about the program can be found on the NSF website.
Carlos Armando Aguila, Ph.D. student in Bioengineering, is a member of the Center of Neuroengineering and Therapeutics, advised by Erin Conrad, Assistant Professor in Neurology, and Brian Litt, Professor in Bioengineering and Neurology. His research focuses on analyzing electroencephalogram (EEG) signals to better understand epilepsy.
Joseph Lance Victoria Casila is a Ph.D. student in Bioengineering in the lab of Riccardo Gottardi, Assistant Professor in Pediatrics and Bioengineering. His research focuses on probing environmental factors that influence stem cell differentiation towards chondrogenesis for cartilage engineering and regeneration.
Trevor Chan is a Ph.D. student in Bioengineering in the lab of Felix Wehrli, Professor of Radiologic Science. His research is in developing computational methods for medical image refinement and analysis. Two ongoing projects are: self-supervised methods for CT super-resolution and assessment of osteoporosis, and semi-supervised segmentation of 3D and 4D echocardiograms for surgical correction of congenital heart-valve defects.
Rakan El-Mayta is an incoming Ph.D. student in the lab of Drew Weissman, Roberts Family Professor in Vaccine Research. Rakan studies messenger RNA-lipid nanoparticle vaccines for the treatment and prevention of infectious diseases. Prior to starting in the Bioengineering graduate program, he worked as a Research Assistant in Weissman lab and in the lab of Michael Mitchell, Associate Professor in Bioengineering.
Austin Jenk is a Ph.D. student in the lab of Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and Bioengineering. Austin aims to develop early intervention, intra-articular therapeutics to combat the onset of post-traumatic osteoarthritis following acute joint injuries. His work focuses on developing a therapeutic that can be employed not only in conventional healthcare settings, but also emergency and battlefield medicine.
Jiageng Liu is a Ph.D. student in the lab of Alex Hughes, Assistant Professor in Bioengineering. His work aims to precisely control the bio-physical/chemical properties of iPSC-derived organoids with advanced synthetic biology approaches to create functional replacement renal tissues.
Alexandra Neeser is a Ph.D. student in the lab of Leyuan Ma, Assistant Professor of Pathology and Laboratory Medicine. Her research focuses on solid tumor microenvironment delivery of therapeutics.
William Karl Selboe Ojemann, a Ph.D. Student in Bioengineering, is a member of the Center for Neuroengineering and Therapeutics directed by Brian Litt, Professor in Bioengineering and Neurology. His research is focused on developing improved neurostimulation therapies for epilepsy and other neurological disorders.
Savan Patel (BSE Class of 2023) conducted research in the lab of Michael Mitchell, Associate Professor in Bioengineering, where he worked to develop lipid nanoparticle formulations for immunotherapy and extrahepatic delivery of mRNA. He will be joining the Harvard-MIT HST MEMP Ph.D. program in the fall of 2023.
David E. Reynolds, a Ph.D. student in Bioengineering, is a member of the lab of Jina Ko, Assistant Professor in Bioengineering and Pathology and Laboratory Medicine. His research focuses on developing novel and translatable technologies to address currently intractable diagnostic challenges for precision medicine.
Andre Roots is a Ph.D. student in the lab of Christopher Madl, Assistant Professor in Materials Science and Engineering. His research focuses on the use of protein engineering techniques and an optimized 3D human skeletal muscle microtissue platform to study the effects of biophysical material properties on cells.
Emily Sharp, a second year Ph.D. student in Bioengineering, is a member of the lab of Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and Bioengineering, part of the McKay Orthopaedic Research Laboratories. Her research focuses on designing multi-functional biomaterials to enhance tissue repair, specifically intervertebral disc repair following herniation and discectomy.
Nat Thurlow is a Ph.D. student in the lab of Louis J. Soslowsky, Fairhill Professor in Orthopedic Surgery and Bioengineering. Their current work focuses on delineating the roles of collagens V and XI in tendon mechanics, fibril structure, and gene expression during tendon development and healing.
Maggie Wagner, Ph.D. student in Bioengineering, is a member in the labs of Josh Baxter, Assistant Professor of Orthopaedic Surgery, and Flavia Vitale, Assistant Professor in Neurology and Bioengineering. Her research focuses on the development of novel sensors to record and monitor muscle neuromechanics.
Presented at the biennial American Peptide Symposium, the Makineni Lectureship Award recognizes an individual who has made a recent contribution of unusual merit to research in the field of peptide science, and is intended to acknowledge original and singular discoveries.
Established in 2003 by an endowment by PolyPeptide Laboratories and Murray and Zelda Goodman, this lectureship honors Rao Makineni, a long-time supporter of peptide science, peptide scientists, and the American Peptide Society.
The distinction is an important one for the assistant professor at the Stuart Weitzman School of Design, for reasons both scientific and artistic. With a doctorate in biomedical engineering, several degrees in architecture, and a devotion to sustainable design, Mogas-Soldevila brings biology to everyday life, creating materials for a future built halfway between nature and artifice.
The architectural technology she describes is unassuming at first look: A freeze-dried pellet, small enough to get lost in your pocket. But this tiny lump of matter, the result of more than a year’s collaboration between designers, engineers and biologists, is a biomaterial that contains a “living-like” system.
When touched by water, the pellet activates and expresses a glowing protein, its fluorescence demonstrating that life and art can harmonize into a third and very different thing, as ready to please as to protect. Woven into lattices made of flexible natural materials promoting air and moisture flow, the pellets form striking interior design elements that could one day keep us healthy.
“We envision them as sensors,” explains Mogas-Soldevila. “They may detect pathogens, such as bacteria or viruses, or alert people to toxins inside their home. The pellets are designed to interact with air. With development, they could monitor or even clean it.”
For now, they glow, a triumphant first stop on the team’s roadmap to the future. The fluorescence establishes that the lab’s biomaterial manufacturing process is compatible with the leading-edge cell-free engineering that gives the pellets their life-like properties.
A rapidly expanding technology, cell-free protein expression systems allow researchers to manufacture proteins without the use of living cells.
Gabrielle Ho, Ph.D. candidate in the Department of Bioengineering and co-leader of the project, explains how the team’s design work came to be cell-free, a technique rarely explored outside of lab study or medical applications.
“Typically, we’d use living E. coli cells to make a protein,” says Ho. “E. coli is a biological workhorse, accessible and very productive. We’d introduce DNA to the cell to encourage expression of specific proteins. But this traditional method was not an option for this project. You can’t have engineered E. coli hanging on your walls.”
Cell-free systems contain all the components a living cell requires to manufacture protein —energy, enzymes and amino acids — and not much else. These systems are therefore not alive. They do not replicate, and neither can they cause infection. They are “living-like,” designed to take in DNA and push out protein in ways that previously were only possible using living cells.
“One of the nicest things about these materials not being alive,” says Mogas-Soldevila, “is that we don’t need to worry about keeping them that way.”
Unlike living cells, cell-free materials don’t need a wet environment or constant monitoring in a lab. The team’s research has established a process for making these dry pellets that preserves bioactivity throughout manufacturing, storage and use.
Bioactive, expressive and programmable, this technology is designed to capitalize on the unique properties of organic materials.
Mogas-Soldevila, whose lab focuses exclusively on biodegradable architecture, understands the value of biomaterials as both environmentally responsible and aesthetically rich.
“Architects are coming to the realization that conventional materials — concrete, steel, glass, ceramic, etc. — are environmentally damaging and they are becoming more and more interested in alternatives to replace at least some of them. Because we use so much, even being able to replace a small percentage would result in a significant reduction in waste and pollution.”
Her lab’s signature materials — biopolymers made from shrimp shells, wood pulp, sand and soil, silk cocoons, and algae gums — lend qualities over and above their sustainable advantages.
“My obsession is diagnostic, but my passion is playfulness,” says Mogas-Soldevila. “Biomaterials are the only materials that can encapsulate this double function observed in nature.”
This multivalent approach benefited from the help of Penn Engineering’s George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, and the support of its director, Sevile Mannickarottu. In addition to contributing essential equipment and research infrastructure to the team, Mannickarottu was instrumental in enabling the interdisciplinary relationships that led the team to success, introducing Ho to the DumoLab Research team collaborators. These include Mogas-Soldevila, Camila Irabien, a Penn Biology major who provided crucial contributions to experimental work, and Fulbright design fellow Vlasta Kubušová, who co-led the project during her time at Penn and who will continue fueling the project’s next steps.
Wangari Mbuthia, Penn Bioengineering Class of 2025, shares her experience in Singapore while studying abroad with the Global Research and Internship Program (GRIP) at Penn. GRIP provides outstanding undergraduate and graduate students the opportunity to intern or conduct research abroad for 8 to 12 weeks over the summer. Participants gain career-enhancing experience and global exposure that is essential in a global workforce.
Engineering Research in Singapore
If someone would have told me this time last year that I would be doing an engineering research program in Singapore, I wouldn’t have believed it. But rest assured here I am, two weeks in, and it has been an incredible experience.
Admittedly before coming to Singapore, basically everything I knew about this country could somewhat be summarized in that it was hot, beautiful and diverse. Before this I had never traveled to an Asian country and I was both excited and nervous about taking this trip. I was excited for food, sights and new experiences but I was also particularly nervous about being in a country where almost no one looks like me. Nevertheless, I decided to travel with an open mind, letting myself wander and wonder as I went and I thought I’d share some of my initial discoveries here.
Walking around Singapore it is clear that it is a place where many cultures have come together – Chinese, Malay, Indian and more – but I could probably count the number of Black people I saw on my two hands. This cultural landscape left me feeling very visible everywhere I went. But at the same time also somewhat invisible because for the most part, no one really made me feel like the odd one out. Rather, my presence only seemed to spark harmless (and sometimes comical) curiosity about where I was from or how I do my braids.
To my delight, the cultural diversity of Singapore is equally reflected in the food options. I can easily have access to almost any type of Asian cuisine at any given time and even quite a lot Western varieties too. I have eagerly been documenting the foods I try and rating them. One of my favorites has been a kaya (a type of sweet coconut spread) toast breakfast with soft-boiled eggs and teh-c (tea with evaporated milk). I also still need to try the unique, smelly fruit (so smelly it is not allowed on public transport), durian.
Another wonderful discovery was to see how Singapore lives up to its name, “garden city”. Not only is the city filled with beautiful buildings each with their own personality, but the city landscape is so artfully integrated with nature inside and out. I have seen indoor gardens and waterfalls but also gorgeous waterfront and outdoor spaces that I could sit in for hours.
It’s hard to believe how a country with such little land area and no natural resources has grown to be one of the richest cities in the world. Singapore truly feels like a place where so much is possible and that has been really special to see.