Tag: CHOP

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Melding AI and RNA: Penn’s $18 Million AIRFoundry to Revolutionize RNA Research

by Ian Scheffler

The NSF AIRFoundry will accelerate RNA research using the power of AI and educate the next generation of RNA researchers. (DesignCells via Getty Images)

In a typical foundry, raw materials like steel and copper are melted down and poured into molds to assume new shapes and functions. The U.S. National Science Foundation Artificial Intelligence-driven RNA Foundry (NSF AIRFoundry), led by the University of Pennsylvania and the University of Puerto Rico and supported by an $18-million, six-year grant, will serve much the same purpose, only instead of smithing metal, the “BioFoundry” will create molecules and nanoparticles.

NSF AIRFoundry is one of five newly created BioFoundries, each of which will have a different focus. Bringing together researchers from Penn Engineering, Penn Medicine’s Institute for RNA Innovation, the University of Puerto Rico–Mayagüez (UPR-M), Drexel University, the Children’s Hospital of Philadelphia (CHOP) and InfiniFluidics, the facility, which will be physically located in West Philadelphia and at UPR-M, will focus on ribonucleic acid (RNA), the tiny molecule essential to genetic expression and protein synthesis that played a key role in the COVID-19 vaccines and saved tens of millions of lives.

The facility will use AI to design, optimize and synthesize RNA and delivery vehicles by augmenting human expertise, enabling rapid iterative experimentation, and providing predictive models and automated workflows to accelerate discovery and innovation.

“With NSF AIRFoundry, we are creating a hub for innovation in RNA technology that will empower scientists to tackle some of the world’s biggest challenges, from health care to environmental sustainability,” says Daeyeon Lee, Russell Pearce and Elizabeth Crimian Heuer Professor in Chemical and Biomolecular Engineering in Penn Engineering and NSF AIRFoundry’s director.

“Our goal is to make cutting-edge RNA research accessible to a broad scientific community beyond the health care sector, accelerating basic research and discoveries that can lead to new treatments, improved crops and more resilient ecosystems,” adds Nobel laureate Drew Weissman, Roberts Family Professor in Vaccine Research in Penn Medicine, Director of the Penn Institute for RNA Innovation and NSF AIRFoundry’s senior associate director.

The facility will catalyze new innovations in the field by leveraging artificial intelligence (AI). AI has already shown great promise in drug discovery, poring over vast amounts of data to find hidden patterns. “By integrating artificial intelligence and advanced manufacturing techniques, the NSF AIRFoundry will revolutionize how we design and produce RNA-based solutions,” says David Issadore, Professor in Bioengineering and in Electrical and Systems Engineering at  Penn Engineering and the facility’s associate director of research coordination.

Read the full story on the Penn AI website.

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Alison Pouch Wins 2024 Cardiac Center Innovation Award

Alison Pouch

Congratulations to Alison Pouch, Assistant Professor in Bioengineering in the School of Engineering and Applied Science, and in Radiology in the Perelman School of Medicine, on winning a 2024 Cardiac Center Innovation Award for scientific research from the Children’s Hospital of Philadelphia (CHOP)’s Philly Spin-In. Pouch’s study, titled “Systemic Semilunar Valve Mechanics and Simulated Repair in Congenital Heart Disease,” is a collaboration with Matthew Jolley, Assistant Professor of Anesthesiology and Critical Care at CHOP:

“Through biomechanical assessment, Drs. Matthew Jolley and Alison Pouch are leading an interdisciplinary CHOP-Penn team that plans to determine why current approaches to systemic semilunar valve (SSV) repair fail. They will also investigate methods to design improved repairs before going to the operating room by using computational simulation to iteratively optimize repair.

‘We believe that understanding biomechanics of abnormal SSVs and explorations of simulated repair will markedly improve our ability to characterize, risk stratify, and surgically treat SSV dysfunction, thereby improving long-term outcomes and quality of life in patients with SSV dysfunction,’ Dr. Jolley said.”

Pouch’s lab focuses on 3D/4D segmentation and modeling of heart valves in echocardiographic images with applications to surgical treatment of valvular regurgitation as part of the Penn Image Computing and Science Laboratory.

Read the full awards announcement in the CHOP Cornerstone Blog.

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2024 Solomon R. Pollack Awards for Excellence in Graduate Bioengineering Research

The Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research is given annually to the most deserving Bioengineering graduate students who have successfully completed research that is original and recognized as being at the forefront of their field. This year, the Department of Bioengineering at the University of Pennsylvania is proud to recognize the work of four outstanding graduates in Bioengineering: William Benman, Alex Chan, Rohan Palanki and Sunghee Estelle Park. 

Read more about the 2024 Solomon R. Pollack awardees and their doctoral research below.

William Benman

Dissertation: “Remote control of cell function using heat and light as inputs”

Will conducts research in the lab of Lukasz Bugaj, Assistant Professor in Bioengineering, focusing on reprogramming cells so that their basic functions can be regulated artificially using heat and/or light as inputs. The goal of this work ranges from clinical applications, such as localized activation of cell therapies within patients via application of heat, to biological manufacturing, using light to activate production of valuable biologics during key phases of a cell’s life cycle. He earned his undergraduate degree in biomedical engineering from Boston University, where he graduated summa cum laude. At BU, he worked in the lab of Wilson Wong, where he was introduced to synthetic biology. During that time, he worked to develop a genetic logic framework that would allow cells to integrate chemical signals, such that each combination of signals would lead to a different, user-defined combination of genes being expressed. Outside of the lab, Benman enjoys baking and sharing his treats with lab members. He mentored the 2021 Penn iGEM team, which recently published their work in Communications Biology. After graduation, he will start a postdoctoral fellowship in Mikhail Shapiro’s lab at Caltech, where he plans to explore electrogenetics, focusing on how to co-opt electrically active cell types to transmit biochemical information out of the body. He is interested in researching ways to get cells to talk to electronic devices and vice/versa for two way communication, especially in the context of patient monitoring and precision therapies. 

“Will’s Ph.D. work broke new ground across several fields, discovering how certain proteins sense temperature, engineering those proteins for on-demand control of human cells, and building devices to allow us to communicate with cells with precision,” says Bugaj. “He has managed these accomplishments while elevating those around him through mentorship, including of graduate students, scores of undergraduates, and even grade-school students in the community. I am immensely proud of Will and what he has accomplished and am gratified by the recognition from the Sol Pollack award.”

Alex Chan

Dissertation: “Engineering small protein based inhibitors and biodegraders for cytosolic delivery and targeting of the undruggable proteome”

Alex conducts research in the lab of Andrew Tsourkas, Professor in Bioengineering and Co-Director, Center for Targeted Therapeutics and Translational Nanomedicine (CT3N). His research focuses on developing novel cancer therapeutics by engineering protein scaffolds so that they can be efficiently delivered into cells using lipid nanocarriers. These proteins can either behave as oncogenic inhibitors or be imbued with E3 domains for targeted protein degradation. He graduated from The Pennsylvania State University in 2018 with a B.S in Biomedical Engineering. There, he conducted undergraduate research on photo-activated silver nanoparticle miRNA delivery systems and wrote his senior honors thesis on this topic. At Penn, Alex served as a wellness co-chair within GABE (the Graduate Association of Bioengineers) and was awarded a graduate research fellowship program award by the National Science Foundation (NSF GRFP). In his spare time, Chan loves to cook and explore the local restaurant scene (and he thinks Philly is one of the most vibrant food meccas in America). Post-graduation, he plans to explore Asia before starting as a Senior Scientist in the biopharma industry. He intends to continue working on novel biologics-based medicines for unmet medical needs.

“I cannot think of anyone more deserving of this award than Alex,” says Tsourkas. “He not only demonstrates all of the traits that we love to see in our most successful Ph.D. students — intelligence, hard work ethic, and perseverance — but Alex has also exhibited a level of scientific independence that is beyond his years. I cannot wait to see what Alex achieves in the future.”

Rohan Palanki

Dissertation: “Ionizable lipid nanoparticles for in utero gene editing of congenital disease”

Rohan completed his B.S. in Bioengineering from Rice University in 2019 and subsequently matriculated into the Medical Scientist Training Program (M.D./Ph.D.) at the University of Pennsylvania. He conducted his doctoral research as an NIH Ruth L. Kirschstein Pre-Doctoral Fellow in the laboratories of Michael J. Mitchell, Associate Professor in Bioengineering, and William H. Peranteau, Associate Professor of Surgery at CHOP. After defending his thesis in 2024, he returned to medical school to complete his clinical training. He plans to pursue a career as a physician-engineer, conducting translational research at the intersection of biomaterials and genomic medicine. Outside of the lab, Palanki enjoys exploring new restaurants in Philadelphia and cheering on Philadelphia sports teams.

“Rohan pioneered new lipid nanoparticle gene editing technology in the lab that can treat deadly childhood diseases before a child is ever born,” says Mitchell. “Rohan is extremely deserving of this award, and I cannot wait to see what he accomplishes as a physician scientist developing new biomaterial and drug delivery technologies for pediatric applications.”

Sunghee Estelle Park

Dissertation: “Engineering stem cells and organoids on a chip for the study of human health and disease”

Sunghee Estelle Park earned her BMSE and MSME from Korea University and her Ph.D. in Bioengineering at the University of Pennsylvania, graduating in July 2023. She conducted doctoral research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering. Her Ph.D. research combined principles in developmental biology, stem cell biology, organoids, and organ-on-a-chip technology to develop innovative in vitro models that can faithfully replicate the pathophysiology of various human diseases. Her doctoral dissertation presented engineering approaches to create stem cell derived three-dimensional (3D) miniature models of human organs on a chip that mimic the physiology and function of living human tissues. Park was appointed Assistant Professor of Biomedical Engineering in the Weldon School of Biomedical Engineering at Purdue University beginning January 2024. Her research lab focuses on using engineered tissues and organoid models to understand how biomechanical and biochemical cues direct stem cell differentiation, maturation, and function during development and disease progression, with a particular emphasis on the lung and intestine. 

“With her deep knowledge, extensive experience, and leadership, Estelle led the major undertaking of harnessing the power of microengineering technologies to create more in vivo-like culture environments in my group, and she played a central role in demonstrating the proof-of-concept of generating organoid-based in vitro models that enable new capabilities for studying complex human diseases and developing new therapeutics,” says Huh. “I am extremely proud of her tremendous accomplishments as a trailblazer in this emerging area and have every confidence that her work as an independent investigator will continue to make great contributions to advancing the field.”

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Riccardo Gottardi Receives BMES Rising Star Award

Riccardo Gottardi, Ph.D.

Riccardo Gottardi, Assistant Professor in Pediatrics and in Bioengineering and leader of the Bioengineering and Biomaterials Laboratory at the Children’s Hospital of Philadelphia (CHOP), received the Rising Star Award from the Biomedical Engineering Society-Cellular and Molecular Bioengineering (BMES-CMBE). The Rising Star Award recognizes a BMES-CMBE member who is at the early independent career stage and has made an outstanding impact on the field of cellular and molecular bioengineering. Awardees will give an oral presentation on their research at the BMES-CMBE conference in Puerto Rico in January and be recognized at the conference Gala dinner.

Dr. Gottardi’s research focuses on engineering solutions for pediatric health, primarily for airway disorders. He has previously received awards for work to create a biomaterial patch to repair the tympanic membrane and for work to develop cartilage implants to treat severe subglottic stenosis. He received grant support from the National Institutes of Health to further his work in subglottic stenosis.

This story originally appeared in the CHOP Cornerstone Blog.

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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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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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Penn Bioengineers Create Non-invasive Cartilage Implants for Pediatric Subglottic Stenosis

by Emily Shafer

Paul Gehret and Riccardo Gottardi accept the International Society for Biofabrication New Investigator Award onstage at the international conference.
Paul Gehret (left) and Riccardo Gottardi, PhD, at Biofabrication 2022, the International Conference on Biofabrication.

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.

This work and similar work on the tympanic membrane earned Paul Gehret, a doctoral student in the Gottardi Lab, the International Society for Biofabrication New Investigator Award and the Wake Forest Institute for Regenerative Medicine Young Investigator Award.  Gehret and Dr. Gottardi accepted the awards at Biofabrication 2022, the International Conference on Biofabrication, in Pisa Italy.

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.”

Read the full story in CHOP’s Cornerstone Blog.

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.

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More 2023 SFB STAR Awards for Penn Bioengineering Students

Following up on our recent announcement of two Student Travel Achievement Recognition (STAR) Awards from the Society for Biomaterials (SFB) for members of the lab of Mike Mitchell, we are pleased to announce that two more Penn Bioengineering students also received STAR Awards!

Matthew Aronson and Alexandra Dumas are both members of the lab of Riccardo Gottardi, Assistant Professor in Pediatrics in the Perelman School of Medicine and in Bioengineering in the School of Engineering and Applied Science. Both presented their work at the recent 2023 SFB Annual Meeting and Exposition in San Diego, California in April 2023 and were honored with STAR Awards for their research.

The Gottardi Bioengineering and Biomaterials Laboratory studies treatment and function restoration for children with otolaryngologic disorders through the Children’s Hospital of Philadelphia  (CHOP) in the Division of Otolaryngology.

Matthew Aronson

Matthew Aronson is a third-year Ph.D. student in Bioengineering, an Ashton Fellow, and a NSF Fellow. His doctoral research focuses on studying pediatric airway diseases and disorders. More specifically, he is interested in how bacteria of the upper airway are responsible for the development and progression the disease subglottic stenosis, narrowing of the airway. In addition to understanding this devastating disease in the context of pediatric patients at CHOP, he also designed a novel drug-eluting endotracheal tube to deliver a selective antimicrobial peptide to function as a treatment modality for the prevention of the disease.

Alexandra Dumas

Alexandra Dumas is a rising fourth-year undergraduate in Bioengineering from Durban, South Africa. She is a PURM Fellow and a University Scholar. Her recent work in the Gottardi Lab focuses on using decellularized cartilage scaffolds to repair the meniscus and airway. After her undergraduate degree, she hopes to pursue a Ph.D. or M.D.-Ph.D. in bioengineering to pursue the design of new biomaterials for low-resource communities.

 

Read more stories featuring Gottardi and his team here.

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2023 Senior Design Project Competition Winners Announced

Each year, Penn Engineering’s seniors present their Senior Design projects, a year-long effort that challenges them to test and develop solutions to real-world problems, to their individual departments. The top three projects from each department go on to compete in the annual Senior Design Competition, sponsored by the Engineering Alumni Society, which involves pitching projects to a panel of judges who evaluate their potential in the market.

We are proud that two of the four awards went to Penn Bioengineering teams!

This year’s panel included over forty judges, and each winning team received a $2,000 prize, generously sponsored by Penn Engineering alumnus Kerry Wisnosky.

Congratulations to all of the 2023 participants and winners!

Technology & Innovation Award

This award recognized the team whose project represents the highest and best use of technology and innovation to leverage engineering principles.

Team BAMBI poses with Dean Vijay Kumar.

Winner: Team BAMBI
Department: Bioengineering
Team Members: Ria Dawar, Pallavi Jonnalagadda, Jessica Ling, Grace Qian
Mentor: Erin Anderson
Instructors: Erin Berlew, Sevile Mannickarottu, and David Meaney
Abstract: BAMBI (Biointelligent Apnea Monitor for Bradycardia-Prone Infants) is a tripartite system that leverages machine learning and automated mechanical stimulation to detect and treat apnea of prematurity in the NICU.

Judges’ Choice Award

Team StablEyes poses with Dean Vijay Kumar.This award recognizes the group whose all-around presentation captures the best of the senior design program’s different facets:  ideation, scope of project, team problem-solving, execution and presentation.

Winner: Team StablEyes
Department: Bioengineering
Team Members: Ella Atsavapranee, Jake Becker, Ruoming Fan, Savan Patel
Mentor: Erin Anderson, Dr. Drew Scoles and Dr. Tomas Aleman (Children’s Hospital of Philadelphia, Penn Medicine)
Instructors: Erin Berlew, Sevile Mannickarottu, and David Meaney
Abstract: StablEyes consists of a stabilization mount that provides fine, motorized control of the handheld OCT to improve ease of use for physicians and machine learning-based software to aid in diagnosis from retinal images.

Read the full list of SEAS Senior Design Competition Award winners in Penn Engineering Today.

Read more about all the Class of 2023 Penn Bioengineering Senior Design Teams in the Penn BE Labs website.

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Senior Design Team “StablEyes” Uses 3D Printing to Simplify Retinal Imaging

A team of Penn Bioengineering Senior Design students was featured as the 3D print of the week by the Penn Biomedical Library’s Biomeditations blog.

The StablEyes team. From left to right, Jake Becker (BE ’23), Ruoming Fan (BE ’23), Ella Atsavapranee (BE ’23), and Savan Patel (M&T ’23).

Fourth-year undergraduate students Ella Atsavapranee, Jake Becker, Ruoming Fan, and Savan Patel created StablEyes, “a stabilization mount that provides fine, motorized control of the handheld OCT to improve ease of use for physicians and machine learning-based software to aid in diagnosis from retinal images.” The team made use of 3D printing services, laboratory space, and expertise across Penn’s campus to create their innovative design, including the Bollinger Digital Fabrication Lab in the Holman Biotech Commons, the Fisher Fine Arts Library, the Children’s Hospital of Philadelphia (CHOP), and the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace (aka the Penn BE Labs).

Read “Featured 3D Print: Simplifying Retinal Imaging with StablEyes” by Lexi Voss in Biomeditations.