Tag: students

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Bioengineering Faculty Member Named ‘Young Innovator’ for Creation of Multiple Myeloma Therapy

by Abbey Porter

Michael Mitchell

Michael J. Mitchell, Associate Professor in Bioengineering at the University of Pennsylvania School of Engineering and Applied Science, has been named a “Young Innovator of Cellular and Molecular Bioengineering” by Cellular and Molecular Bioengineering, the journal of the Biomedical Engineering Society (BMES).

The award recognizes faculty who are conducting some of the most innovative and impactful studies in the field of biomedical engineering. Recipients will present their research and be officially recognized at the BMES Annual Meeting in October.

Mitchell is being honored for creating an RNA nanoparticle therapy that stops the spread of the deadly bone marrow cancer multiple myeloma and helps to eliminate it altogether. Known for being difficult to treat, the disease kills over 100,000 people every year.

“We urgently need innovative, effective therapies against this cancer,” Mitchell says. “The nanotechnology we developed can potentially serve as a platform to treat multiple myeloma and other bone marrow-based malignancies.”

Mitchell, along with Christian Figuerora-Espada, a doctoral student in Bioengineering, previously published a study in PNAS describing how their RNA nanoparticle therapy stops multiple myeloma from moving through the blood vessels and mutating. In their current paper in Cellular and Molecular Bioengineering, which expands upon this RNA nanoparticle platform, they show that inhibition of both multiple myeloma migration and adhesion to bone marrow blood vessels, combined with an FDA-approved multiple myeloma therapeutic, extends survival in a mouse model of multiple myeloma.

Read more in Penn Engineering Today.

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Sonura Named Among 2023 PHL Inno Under 25 Honorees

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce

A team of recent Penn Bioengineering graduates have been included in list of prominent young Philadelphia innovators as chosen by The Philadelphia Business Journal and PHL Inno.

Gabriella Daltoso, Sophie Ishiwari, Gabriela Cano, Caroline Amanda Magro, and Tifara Eliana Boyce founded Sonura as their Senior Design Project in Bioengineering. The team, who all graduated in 2023, picked up a competitive President’s Innovation Prize for their beanie that promotes the cognitive and socioemotional development of newborns in the NICU by protecting them from the auditory hazards of their environments while fostering parental connection. Now, they have been included in the list of fourteen Inno Under 25 honorees for 2023.

“To determine this year’s list, the Philadelphia Business Journal and PHL Inno sought nominations from the public and considered candidates put forth by our editorial team. To be considered, nominees must be 25 years of age or younger and work for a company based in Greater Philadelphia and/or reside in the region.

Honorees span a wide range of industries, including consumer goods, biotechnology and environmental solutions. Many are products of the region’s colleges and universities, though some studied farther afield before setting up shop locally.”

Read “Announcing the 2023 PHL Inno Under 25 honorees” and “Inno Under 25” in PHL Inno. Penn affiliates can subscribe through Penn’s library services.

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The Physics of Fat Droplets Reveal DNA Danger

by Devorah Fischler

Fat is a normal and necessary part of the body. Fat cells store and release energy, as well as play significant roles in hormonal regulation and immunity.

Engineers and scientists at the University of Pennsylvania are the first to discover fat-filled lipid droplets’ (pictured above in green) surprising capability to indent and puncture the nucleus, the organelle which contains and regulates a cell’s DNA.

In recent decades, a concerning rise in metabolic illnesses – such as cardiovascular disease, high blood pressure and diabetes – has focused scientific attention on the biology and chemistry of fat, resulting in a wealth of information about how fat cells work.

But fat cells and their metabolic activities are only part of the story.

Fat-filled lipid droplets, tiny spheres of fat many times smaller than fat cells, are a growing subject of scientific interest. Found inside many different cell types, these lipid particles have long been little understood. Studies have begun to illuminate these droplets’ participation in metabolic functions and cellular protection, but we still know next to nothing about the physical nature of fat.

Now, researchers at the University of Pennsylvania School of Engineering and Applied Science have looked beyond biochemistry to publish groundbreaking work on the physics of these droplets, revealing them to be a potential threat to a cell’s nucleus. In the August issue of the Journal of Cell Biology, they are the first to discover fat-filled lipid droplets’ surprising capability to indent and puncture the nucleus, the organelle which contains and regulates a cell’s DNA.

The stakes of their findings are high: a ruptured nucleus can lead to elevated DNA damage that is characteristic of many diseases, including cancer.

The study was led by Dennis E. Discher, Robert D. Bent Professor in the Department of Chemical and Biomolecular Engineering, Bioengineering, and in Mechanical Engineering and Applied Mechanics, Irena Ivanovska, Ph.D. research associate in Penn’s Molecular and Cell Biophysics Lab, and Michael Tobin, Ph.D. candidate in the Department of Bioengineering.

“Intuitively, people think of fat as soft,” says Discher. “And on a cellular level it is. But at this small size of droplet— measuring just a few microns rather than the hundreds of microns of a mature fat cell—it stops being soft. Its shape has a much higher curvature, bending other objects very sharply. This changes its physics in the cell. It can deform. It can damage. It can rupture.”

Read the full story in Penn Engineering Today.

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SCALAR: A Microchip Designed to Transform the Production of mRNA Therapeutics and Vaccines

Led by Michael Mitchell and David Issadore of the School of Engineering and Applied Science, a team of researchers has developed a platform that could rapidly accelerate the development of mRNA-based lipid nanoparticle vaccines and therapeutics at both the small and large scale, SCALAR. (Image: iStock / Anatoly Morozov)

Following the global COVID-19 pandemic, the development and rapid deployment of mRNA vaccines highlighted the critical role of lipid nanoparticles (LNPs) in the context of pharmaceuticals. Used as the essential delivery vehicles for fragile RNA-based therapies and vaccines, LNPs protect the RNA from degradation and ensure effective delivery within the body.

Despite their critical importance, the large-scale manufacturing of these LNPs saw numerous bottlenecks during the pandemic, underscoring the need for scalable production techniques that could keep pace with global demand.

Now, in a paper published in the Proceedings of the National Academy of the Sciences, researchers at the University of Pennsylvania describe how the Silicon Scalable Lipid Nanoparticle Generation platform (SCALAR), a reusable silicon- and glass-based platform designed to transform the production landscape of LNPs for RNA therapeutics and vaccines, offers a scalable and efficient solution to the challenges exposed during the COVID-19 crisis.

“We’re excited to create a piece of technology platform that bridges the gap between small-scale discovery and large-scale manufacturing in the realm of RNA lipid nanoparticle vaccines and therapeutics,” says co-author Michael Mitchell, associate professor of bioengineering in the School of Engineering and Applied Science at Penn. “By doing so, we’ve effectively leapfrogged the clunky, time-consuming, and costly barriers that slow down the production ramp-up of promising new RNA medicines and vaccines.”

The intricacies of RNA-based therapies require the RNA to be encased in a delivery system capable of navigating the body’s biological obstacles. LNPs fulfill this role, allowing the RNA to reach the intended cells for maximum therapeutic impact. SCALAR aims to take this a step further, allowing for an unprecedented three orders of magnitude scalability in LNP production rates, addressing the speed and consistency bottlenecks that hinder existing methods.

Sarah Shepherd, the first author of the paper and a recent Ph.D. graduate who worked in the Mitchell Lab, says, “With SCALAR, we’re not just reacting to today’s challenges but proactively preparing for tomorrow’s opportunities and crises. This technology is flexible, uses mixing architectures well-documented in microfluidics, and is scalable enough to meet future demands in real time. That’s an enormous leap forward for the field.”

Shepherd says that SCALAR builds on prior work from the Mitchell lab and is based on a microfluidic chip platform. Akin to a computer chip, wherein a computer’s electrically integrated circuit has numerous little transistors transporting signals as ones or zeroes to produce an output, the SCALAR microchip precisely controls their two key reagents, lipids and RNA, to generate LNPs.

Read the full story in Penn Today.

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Penn and CHOP Researchers Show Gene Editing Tools Can be Delivered to Perinatal Brain

Genetic diseases that involve the central nervous system (CNS) often impact children before birth, meaning that once a child is born, irreversible damage has already been done. Given that many of these conditions result from a mutation in a single gene, there has been growing interest in using gene editing tools to correct these mutations before birth.

However, identifying the appropriate vehicle to deliver these gene editing tools to the CNS and brain has been a challenge. Viral vectors used to deliver gene therapies have some potential drawbacks, including pre-existing viral immunity and vector-related adverse events, and other options like lipid nanoparticles (LNPs) have not been investigated extensively in the perinatal brain.

Now, researchers in the Center for Fetal Research at Children’s Hospital of Philadelphia (CHOP) and Penn Engineering have identified an ionizable LNP that can deliver mRNA base editing tools to the brain and have shown it can mitigate CNS disease in perinatal mouse models. The findings, published in ACS Nano, open the door to mRNA therapies that could be delivered pre- or postnatally to treat genetic CNS diseases.

The research team began by screening a library of ionizable LNPs – microscopic fat bubbles that have a positive charge at low pH but neutral charge at physiological conditions in the body. After identifying which LNPs were best able to penetrate the blood-brain barrier in fetal and newborn mice, they optimized their top-performing LNP to be able to deliver base editing tools. The LNPs were then used to deliver mRNA for an adenine base editor, which would correct a disease-causing mutation in the lysosomal storage disease, MPSI, by changing the errant adenine to guanine.

The researchers showed that their LNP was able to improve the symptoms of the lysosomal storage disease in the neonatal mouse brain, as well as deliver mRNA base editing tools to the brain of other animal models. They also showed the LNP was stable in human cerebrospinal fluid and could deliver mRNA base editing tools to patient-derived brain tissue.

“This proof-of-concept study – co-led by Rohan Palanki, an MD/PhD student in my lab, and Michael Mitchell’s lab at Penn Bioengineering – supports the safety and efficacy of LNPs for the delivery of mRNA-based therapies to the central nervous system,” said co-senior author William H. Peranteau, MD, an attending surgeon in the Division of General, Thoracic and Fetal Surgery at CHOP and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery. “Taken together, these experiments provide the foundation for additional translational studies and demonstrate base editing facilitated by a nonviral delivery carrier in the NHP fetal brain and primary human brain tissue.”

This story was written by Dana Bate. It originally appeared on CHOP’s website.

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Penn Bioengineers Recommend Improvements to Science Communication

Three graduate students in Bioengineering have collaborated to craft a list of recommendations to improve science communication during national health emergencies.

Doctoral students Miles J. Arnett, Dimitris Boufidis, and Melanie Hilman are part of the Penn Science Policy and Diplomacy Group (PSPDG), student organization which creates opportunities for students to get hands-on experience in Science Policy, Diplomacy, and Communication.

Their brief reviews the public health response to the COVID-19 pandemic and recommends specific improvements to science policy and communication by national scientific institutions:

“The public health response to the pandemic was dramatically weakened by an uncoordinated communication strategy, inconsistent messaging, and fractured media environments. These shortcomings had a real human cost, with an estimated hundreds of thousands of Americans dying as a consequence of high rates of vaccine hesitancy. Now, in the aftermath of the pandemic, we have a chance to learn from this crisis and develop a more robust science communication infrastructure for future health emergencies.“

Read “From Chaos to Clarity: Reinventing Science Communication After COVID-19” at Medium.

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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 Psychedelics Simultaneously Treat Chronic Pain and Depression?

Ahmad Hammo

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 is working under the guidance of neuroanesthesiologist and neuroscientist Joseph Cichon, an assistant professor in the Perelman School of Medicine. The effort is supported by the Penn Undergraduate Research Mentoring (PURM) program, administered by the Center for Undergraduate Research and Fellowships, which awards undergraduate students $5,000 to spend 10 weeks conducting research alongside Penn faculty.

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.”

Read the full story in Penn Today.

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Riccardo Gottardi Recognized for Airway Research

Matthew Aronson (left), Ph.D. student in Bioengineering, and Riccardo Gottardi, Assistant Proessor in Bioengineering and Pediatrics.

Riccardo Gottardi, Assistant Professor in Pediatrics in the Perelman School of Medicine and in Bioengineering in the School of Engineering and Applied Science, has been named a “Young Innovator of Cellular and Molecular Bioengineering” by Cellular and Molecular Bioengineering, the official journal of the Biomedical Engineering Society (BMES). Gottardi is Chief Scientist in the Pediatric Airway Frontier Program at the Children’s Hospital of Philadelphia (CHOP). He leads the Bioengineering and Biomaterials (Bio2) Lab, and was recognized here for his research to prevent subglottic stenosis in children.

Gottardi’s work in subglottic stensosis, a severe narrowing of the airway in response to intubation, was recently profiled in CHOP’s Cornerstone Blog. CHOP’s award press release describes Gottardi’s innovative treatment:

“Prior studies by Dr. Gottardi’s lab used in vitro models to demonstrate that incorporating AMPs into polymer-coated tubes can inhibit bacterial growth and modulate the upper-airway microbiome. In a recent study in Cellular and Molecular Engineering, led by [Bioengineering] PhD student Matthew Aronson of the Gottardi Lab, the researchers went a step further and used both ex vivo and in vivo models to show how their patent-pending antimicrobial peptide-eluting endotracheal tube (AMP-ET) effectively targeted the local airway microbiota, reducing inflammation and resolving stenosis.

‘I am honored to be recognized by Cellular and Molecular Engineering for this exciting and notable award,” Dr. Gottardi said. “We are hopeful that our airway innovation will show similar success in human trials, so that we can improve outcomes for intubated pediatric patients.’”

Read CHOP’s full announcement of the award here.

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“QR Code for Cancer Cells” – Uncovering Why Some Cells Become Resistant to Anti-Cancer Therapies

by Win Reynolds

QR codeA 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 findings were recently published in Nature.

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.”

Read the full story in Penn Engineering Today.