Category: interview

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Little Bots That Could Put a Stop to Infectious Disease

Image: Courtesy of iStock / K_E_N

Biofilms—structured communities of microorganisms that create a protective matrix shielding them from external threats, including antibiotics—are responsible for about 80% of human infections and present a significant challenge in medical treatments, often resisting conventional methods.

In a Q&A with Penn Today, Hyun (Michel) Koo of the School of Dental Medicine and Edward Steager of the School of Engineering and Applied Science at Penn discuss an innovative approach they’ve partnered on: the use of small-scale robotics, microrobots, to offer a promising solution to tackle these persistent infections, bringing new capabilities and precision to the field of biomedical engineering.

Q: What is the motivation behind opting for tiny robots to tackle infections?

Koo: Treating biofilms is a broad yet unresolved biomedical problem, and conversely, the strategies for tackling biofilms are limited for a number of reasons. For instance, biofilms typically occur on surfaces that can be tricky to reach, like between the teeth in the oral cavity, the respiratory tract, or even within catheters and implants, so treatments for these are usually restricted to antibiotics (or antimicrobials) and other physical methods reliant on mechanical disruption. However, this touches on the problem of antimicrobial resistance: targeting specific microorganisms present in these structures is difficult, so antibiotics often fail to reach and penetrate the biofilm’s protective layers, leading to persistent infections and increased risk of antibiotic resistance.

We needed a way to circumvent these constraints, so Ed and I teamed up in 2017 to develop new, more precise and effective approaches that leverage the engineers’ ability to generate solutions that we, the clinicians and life science researchers, identify.

Read the full interview in Penn Today.

Hyun (Michel) Koo is a professor in the Department of Orthodontics and in the divisions of Pediatric Dentistry and Community Oral Health and the co-founder of the Center for Innovation & Precision Dentistry in the School of Dental Medicine at the University of Pennsylvania. He is a member of the Penn Bioengineering Graduate Group.

Edward Steager is a senior research investigator in Penn’s School of Engineering and Applied Science.

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Innovation and Impact: “RNA: Past, Present and Future”

by Melissa Pappas

(Left to right): Mike Mitchell, Noor Momin, and David Meaney recording the Innovation & Impact podcast.

In the most recent episode of the Penn Engineering podcast Innovation & Impact, titled “RNA: Past, Present and Future,” David F. Meaney, Senior Associate Dean of Penn Engineering and Solomon R. Pollack Professor in Bioengineering, is joined by Mike Mitchell, Associate Professor in Bioengineering, and Noor Momin, who will be joining Penn Engineering as an Assistant Professor in Bioengineering early next year, to discuss the impact that RNA has had on health care and biomedical engineering technologies.

Mitchell outlines his lab’s research that spans drug delivery, new technology in protecting RNA and its applications in treating cancer. Momin details her research, which is focused on optimizing the immune system to protect against illnesses such as cardiovascular diseases and cancer. With Meaney driving the discussion around larger questions, including the possibility of a cancer vaccine, the three discuss what they are excited about now and where the field is going in the future with these emerging, targeted treatments.

Read the full story in Penn Engineering Today.

Subscribe to the Innovation & Impact podcast on Apple Music, Spotify or your favorite listening platforms or find all the episodes on the Penn Engineering YouTube channel.

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Harnessing Artificial Intelligence for Real Biological Advances—Meet César de la Fuente

by Eric Horvath

In an era peppered by breathless discussions about artificial intelligence—pro and con—it makes sense to feel uncertain, or at least want to slow down and get a better grasp of where this is all headed. Trusting machines to do things typically reserved for humans is a little fantastical, historically reserved for science fiction rather than science. 

Not so much for César de la Fuente, PhD, the Presidential Assistant Professor in Psychiatry, Microbiology, Chemical and Biomolecular Engineering, and Bioengineering in Penn’s Perelman School of Medicine and School of Engineering and Applied Science. Driven by his transdisciplinary background, de la Fuente leads the Machine Biology Group at Penn: aimed at harnessing machines to drive biological and medical advances. 

A newly minted National Academy of Medicine Emerging Leaders in Health and Medicine (ELHM) Scholar, among earning a host of other awards and honors (over 60), de la Fuente can sound almost diplomatic when describing the intersection of humanity, machines and medicine where he has made his way—ensuring multiple functions work together in harmony. 

“Biology is complexity, right? You need chemistry, you need mathematics, physics and computer science, and principles and concepts from all these different areas, to try to begin to understand the complexity of biology,” he said. “That’s how I became a scientist.”

Read the full story in Penn Medicine News.

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Carl June on the Boundless Potential of CAR T Cell Therapy

by Meagan Raeke

Carl June, at the flash mob celebration of the FDA approval of the CAR T cell therapy he developed, in August 2017. (Image: Courtesy of Penn Medicine Magazine)

For most of modern medicine, cancer drugs have been developed the same way: by designing molecules to treat diseased cells. With the advent of immunotherapy, that changed. For the first time, scientists engineered patients’ own immune systems to recognize and attack diseased cells.

One of the best examples of this pioneering type of medicine is CAR T cell therapy. Invented in the Perelman School of Medicine by Carl June, the Richard W. Vague Professor in Immunotherapy, CAR T cell therapy works by collecting T cells from a patient, modifying those cells in the lab so that they are designed to destroy cancerous cells, and reinfusing them into the patient. June’s research led to the first FDA approval for this type of therapy, in 2017. Six different CAR T cell therapies are now approved to treat various types of blood cancers. Carl June, at the flash mob celebration of the FDA approval of the CAR T cell therapy he developed, in August 2017. (Image: Courtesy of Penn Medicine Magazine)

CAR T cell therapy holds the potential to help millions more patients—if it can be successfully translated to other conditions. June and colleagues, including Daniel Baker, a fourth-year doctoral student in the Cell and Molecular Biology department, discuss this potential in a perspective published in Nature.

In the piece, June and Baker highlight other diseases that CAR T cell therapy could be effective.

“CAR T cell therapy has been remarkably successful for blood cancers like leukemias and lymphomas. There’s a lot of work happening here at Penn and elsewhere to push it to other blood cancers and to earlier stage disease, so patients don’t have to go through chemo first,” June says. “Another big priority is patients with solid tumors because they make up the vast majority of cancer patients. Beyond cancer, we’re seeing early signs that CAR T cell therapy could work in autoimmune diseases, like lupus.”

As for which diseases to pursue as for possible future treatment, June says, “essentially it boils down to two questions: Can we identify a population of cells that are bad? And can we target them specifically? Whether that’s asthma or chronic diseases or lupus, if you can find a bad population of cells and get rid of them, then CAR T cells could be therapeutic in that context.”

“What’s exciting is it’s not just theoretical at this point. There have been clinical reports in other autoimmune diseases, including myasthenia gravis and inflammatory myopathy,” Baker says. “But we are seeing early evidence that CAR T cell therapy will be successful beyond cancer. And it’s really opening the minds of people in the field to think about how else we could use CAR T. For example, there’s some pioneering work at Penn from the Epstein lab for heart failure. The idea is that you could use CAR T cells to get rid of fibrotic tissue after a cardiac injury, and potentially restore the damage following a heart attack.”

Baker adds, “there’s no question that over the last decade, CAR T cell therapy has revolutionized cancer. I’m hoping to play a role in bringing these next generation therapies to patients and make a real impact over the next decade. I think there’s potential for cell therapy to be a new pillar of medicine at large, and not just a new pillar of oncology.”

Read the full story at Penn Medicine Today.

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Student Spotlight: Cosette Tomita

Cosette TomitaCosette 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.”

Read the full Q&A at the Penn Engineering Graduate Admissions website.

Mark Sellmeyer is Assistant Professor of Radiology in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group.

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Could the Age of the Universe Be Twice as Old as Current Estimates Suggest?

by Nathi Magubane

NASA’s James Webb Space Telescope has produced the deepest and sharpest infrared image of the distant universe to date. Known as Webb’s First Deep Field, this image of galaxy cluster SMACS 0723 is rich with detail. Thousands of galaxies—including the faintest objects ever observed in the infrared—have appeared in Webb’s view for the first time. The image shows the galaxy cluster SMACS 0723 as it appeared 4.6 billion years ago. The combined mass of this galaxy cluster acts as a gravitational lens, magnifying much more distant galaxies behind it. Webb’s Near-Infra Red Cam has brought those distant galaxies into sharp focus—they have tiny, faint structures that have never been seen before, including star clusters and diffuse features. (Image: NASA, ESA, CSA, and STScI)

Could the universe be twice as old as current estimates put forward? Rajendra Gupta of the University of Ottawa recently published a paper suggesting just that. Gupta claims the universe may be around 26.7 billion years rather than the commonly accepted 13.8 billion. The news has generated many headlines as well as criticism from astronomers and the larger scientific community.

Penn Today met with professors Vijay Balasubramanian and Mark Devlin to discuss Gupta’s findings and better understand the rationale of these claims and how they fit in the broader context of problems astronomers are attempting to solve.

How do we know how old the universe actually is?

Balasubramanian: The universe is often reported to be 13.8 billion years old, but, truth be told, this is an amalgamation of various measurements that factor in different kinds of data involving the apparent ages of ‘stuff’ in the universe.

This stuff includes observable or ordinary matter like you, me, galaxies far and near, stars, radiation, and the planets, then dark matter—the sort of matter that doesn’t interact with light and which makes up about 27% of the universe—and finally, dark energy, which makes up a massive chunk of the universe, around 68%, and is what we believe is causing the universe to expand.

And so, we take as much information as we can about the stuff and build what we call a consensus model of the universe, essentially a line of best fit. We call the model the Lambda Cold Dark Matter (ΛCDM).

Lambda represents the cosmological constant, which is linked to dark energy, namely how it drives the expansion of the universe according to Einstein’s theory of general relativity. In this framework, how matter and energy behave in the universe determines the geometry of spacetime, which in turn influences how matter and energy move throughout the cosmos. Including this cosmological constant, Lambda, allows for an explanation of a universe that expands at an accelerating rate, which is consistent with our observations.

Now, the Cold Dark Matter part represents a hypothetical form of dark matter. ‘Dark’ here means that it neither interacts with nor emits light, so it’s very hard to detect. ‘Cold’ refers to the fact that its particles move slowly because when things cool down their components move less, whereas when they heat up the components get excited and move around more relative to the speed of light.

So, when you consider the early formation of the universe, this ‘slowness’ influences the formation of structures in the universe like galaxies and clusters of galaxies, in that smaller structures like the galaxies form before the larger ones, the clusters.

Devlin: And then taking a step back, the way cosmology works and pieces how old things are is that we look at the way the universe looks today, how all the structures are arranged within it, and we compare it to how it used to be with a set of cosmological parameters like Cosmic Microwave Background (CMB) radiation, the afterglow of the Big Bang, and the oldest known source of electromagnetic radiation, or light. We also refer to it as the baby picture of the universe because it offers us a glimpse of what it looked like at 380,000 years old, long before stars and galaxies were formed.

And what we know about the physical nature of the universe from the CMB is that it was something really smooth, dense, and hot. And as it continued to expand and cool, the density started to vary, and these variations became the seeds for the formation of cosmic structures.
The denser regions of the universe began to collapse under their own gravity, forming the first stars, galaxies, and clusters of galaxies. So, this is why, when we look at the universe today, we see this massive cosmic web of galaxies and clusters separated by vast voids. This process of structure formation is still ongoing.

And, so, the ΛCDM model suggests that the primary driver of this structure formation was dark matter, which exerts gravity and which began to clump together soon after the Big Bang. These clumps of dark matter attracted the ordinary matter, forming the seeds of galaxies and larger cosmic structures.

So, with models like the ΛCDM and the knowledge of how fast light travels, we can add bits of information, or parameters, and we have from things like the CMB and other sources of light in our universe, like the ones we get from other distant galaxies, and we see this roadmap for the universe that gives us it’s likely age. Which we think is somewhere in the ballpark of 13.8 billion years.

Read the full Q&A in Penn Today.

Vijay Balasubramanian is the Cathy and Marc Lasry Professor in the Department of Physics and Astronomy in the School of Arts & Sciences at the University of Pennsylvania. He is a member of the Penn Bioengineering Graduate Group.

Mark Devlin is the Reese W. Flower Professor of Astronomy and Astrophysics in the Department of Physics and Astronomy in the School of Arts & Sciences at Penn.

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The Potential Futures of Neurotech

Roy Hoshi Hamilton, MD, MS, FAAN, FANA

Brain technology offers all kinds of exciting possibilities — from treating conditions like epilepsy or depression, to simply maximizing brain health. But medical ethicists are concerned about potential dangers and privacy concerns. Roy Hamilton, Professor of Neurology in the Perelman School of Medicine,  Director of the Penn Brain Science, Translation, Innovation, and Modulation (BrainSTIM) Center, and member of the Penn Bioengineering Graduate Group, spoke with WHYY about how brain stimulation is being used.

Listen to “Neurotech and the Growing Battle for Our Brains“

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Safe and Sound: Sonura Supports Newborn Development by Sequestering Disruptive Noise

by Nathi Magubane

Recipients of the 2023 President’s Innovation Prize, team Sonura, five bioengineering graduates from the School of Engineering and Applied Science, have created a device that filters out disruptive environmental noises for infants in neonatal intensive care units. Their beanie offers protection and fosters parental connection to newborns while also supporting their development.

Machines beeping and whirring in a rhythmic chorus, the droning hum of medical equipment, and the bustles of busy health care providers are the familiar sounds of an extended stay at a hospital. This cacophony can create a sense of urgency for medical professionals as they move about with focused determination, closely monitoring their patients, but for infants in neonatal intensive care units (NICU) this constant noise can be overwhelming and developmentally detrimental.

Enter Tifara Boyce, from New York City; Gabriela Cano, from Lawrenceville, New Jersey; Gabriella Daltoso, from Boise, Idaho; Sophie Ishiwari, from Chicago, and Caroline Magro, from Alexandria, Virginia, bioengineering graduates from the School of Engineering and Applied Science, who have created the Sonura Beanie. Their device filters out harmful noises for NICU infants while supporting cognitive and socioemotional development by allowing parents to send voice messages to their newborns.

The Sonura team members are recipients of the 2023 President’s Innovation Prize, which includes an award of $100,000 and an additional $50,000 living stipend per team member. The recent graduates will spend the year developing their product.

“The Penn engineers behind Sonura are determined to make a difference in the world,” says President Liz Magill. “They identified a substantial medical challenge that affects many parents and their newborn children. With the guidance of their mentors, they are taking key steps to address it and in doing so are improving the developmental prospects for children in the NICU. I am proud the University is able to support their important work.”

The Sonura Beanie’s creation began in the Stephenson Foundation Educational Laboratory and Bio-MakerSpace as a part of the Bioengineering Senior Design class project.

Prototype of the Sonura Beanie. (Image: Courtesy of the Sonura team)

She was particularly struck by the noisiness of the environment and considered the neurodevelopmental outcomes that may arise following long-term exposure to the harsh sounds at a critical developmental stage for infants. This concern prompted Magro to consult her team about potential solutions.

“I was really eager to tackle this problem because it bears some personal significance to me,” says Cano, who works on the device’s mobile application. “My sister was a NICU baby who was two months premature, so, when Caroline and I started talking about the issues a disruptive environment could cause, it seemed like the pieces of a puzzle started to come together.”

Read the full story in Penn Today.

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The Big Bang at 75

by Kristina García

A child stops by an image of the cosmic microwave background at Shanghai Astronomy Museum in Shanghai, China on July 18, 2021. (Image: FeatureChina via AP Images)
A girl stops by an image of the cosmic microwave background (CMB) at Shanghai Astrology Museum in Shanghai, China Sunday, Jul. 18, 2021. The planetarium, with a total floor space of 38,000 square meters and claimed to be the world’s largest, opens to visitors from July 18. (FeatureChina via AP Images)

There was a time before time when the universe was tiny, dense, and hot. In this world, time didn’t even exist. Space didn’t exist. That’s what current theories about the Big Bang posit, says Vijay Balasubramanian, the Cathy and Marc Lasry Professor of Physics. But what does this mean? What did the beginning of the universe look like? “I don’t know, maybe there was a timeless, spaceless soup,” Balasubramanian says. When we try to describe the beginning of everything, “our words fail us,” he says.

Yet, for thousands of years, humans have been trying to do just that. One attempt came 75 years ago from physicists George Gamow and Ralph Alpher. In a paper published on April 1, 1948, Alpher and Gamow imagined the universe starts in a hot, dense state that cools as it expands. After some time, they argued, there should have been a gas of neutrons, protons, electrons, and neutrinos reacting with each other and congealing into atomic nuclei as the universe aged and cooled. As the universe changed, so did the rates of decay and the ratios of protons to neutrons. Alpher and Gamow were able to mathematically calculate how this process might have occurred.

Now known as the alpha-beta-gamma theory, the paper predicted the surprisingly large fraction of helium and hydrogen in the universe. (By weight, hydrogen comprises 74% of nuclear matter, helium 24%, and heavier elements less than 1%.)

The findings of Gamow and Alpher hold up today, Balasubramanian says, part of an increasingly complex picture of matter, time and space. Penn Today spoke with Balasubramanian about the paper, the Big Bang, and the origin of the universe.

Read the full Q&A in Penn Today.

Balasubramanian is Cathy and Marc Lasry Professor in the Department of Physics and Astronomy in the Penn School of Arts and Sciences and a member of the Penn Bioengineering Graduate Group.

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Student Spotlight: Jerry Gao

Ego of the Week: Jerry Gao
Jerry Gao (photo credit: Nathaniel Babitts)

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.'”

Read “Ego of the Week: Jerry Gao” in 34th Street.