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.

AI-guided Brain Stimulation Aids Memory in Traumatic Brain Injury

by Erica Moser

Illustration of a human brain
Image: iStock/Ogzu Arslan

Traumatic brain injury (TBI) has disabled 1 to 2% of the population, and one of their most common disabilities is problems with short-term memory. Electrical stimulation has emerged as a viable tool to improve brain function in people with other neurological disorders.

Now, a new study in the journal Brain Stimulation shows that targeted electrical stimulation in patients with traumatic brain injury led to an average 19% boost in recalling words.

Led by University of Pennsylvania psychology professor Michael Jacob Kahana, a team of neuroscientists studied TBI patients with implanted electrodes, analyzed neural data as patients studied words, and used a machine learning algorithm to predict momentary memory lapses. Other lead authors included Wesleyan University psychology professor Youssef Ezzyat and Penn research scientist Paul Wanda.

“The last decade has seen tremendous advances in the use of brain stimulation as a therapy for several neurological and psychiatric disorders including epilepsy, Parkinson’s disease, and depression,” Kahana says. “Memory loss, however, represents a huge burden on society. We lack effective therapies for the 27 million Americans suffering.”

Read the full story in Penn Today.

Michael Kahana is the Edmund J. and Louise W. Kahn Term Professor of Psychology at the University of Pennsylvania. He is a member of the Penn Bioengineering Graduate Group.

Artificial Intelligence is Leveling Up the Fight Against Infectious Diseases

by

Image credit: NIAID

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.

Cesar de la Fuente brings an expert eye to how AI has transformed infectious disease research in a recently published piece in Science with co-authors Felix Wong and James J. Collins from MIT.

Presidential Assistant Professor in the Department of Bioengineering and the Department of Chemical and Biomolecular Engineering at the University of Pennsylvania School of Engineering and Applied Science, with additional primary appointments in Psychiatry and Microbiology within the Perelman School of Medicine, de la Fuente brings a multifaceted perspective to his survey of the field.

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.

Read more in Penn Engineering Today.

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.

Why New Cancer Treatments are Proliferating

by Karen L. Brooks

Doctors performing surgery.
Image: Penn Medicine News

In the five years since the FDA’s initial approval of chimeric antigen receptor (CAR) T cell therapy, Penn Medicine has gleaned 20 additional approvals related to drugs and techniques to treat or detect cancer.

Rather than being the single disease class many people refer to, “cancer” is a blanket term that covers more than 100 distinct diseases, many of which have little in common aside from originating with rapidly dividing cells. Since different cancers demand different treatments, it follows that any given new therapy emerging from any institution would be likely to be a new cancer treatment.

But why so many in just this five-year period?

The volume of new cancer treatments makes sense, says Abramson Cancer Center (ACC) director Robert Vonderheide, attributing the flurry of new cancer drug approvals to a recent “explosion” in knowledge about cancer biology.

“Much of that knowledge is about the immune system’s ability to attack cancer, which people seriously doubted until about 20 years ago. As soon as we had a clinical validation for this Achilles heel in cancer, the dam burst for ideas about other ways to exploit that vulnerability to come forward,” he says. “The first drug that came out to activate the immune system inspired the rest of the field to find the next drug, and the one after that. We as a field have moved from serendipity and empiricism to science-driven drug design.”

The first CAR T cell therapy approval invigorated Penn faculty interested in finding new ways to harness the immune system to fight cancer.

“An approval like that makes what you’re working on more of a reality,” says Avery Posey, an assistant professor of systems pharmacology and translational therapeutics in the Perelman School of Medicine, whose lab team spends much of its time trying to identify more specific antigens for solid tumors and also studies ways to optimize engineered donor T cells. “It brings a new perspective, showing that your work is more than basic research and can actually become drugs that impact patients’ lives. That’s a real motivator to keep pushing forward.”

Honing new immunotherapies is a priority among Penn researchers, but not every recently approved new cancer treatment or detection tool developed at the institution engages the immune system. Faculty have explored and introduced widely varying approaches to improving the standard of care for cancer patients.

Read the full story in Penn Medicine Magazine.

Avery Posey is a member of the Penn Bioengineering Graduate Group. Read more stories featuring Posey here.

2023 Graduate Research Fellowships for Bioengineering Students

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.

Breaking Down Barriers to Blood Donation for LGBTQ+ People

by Meredith Mann

Close-up of a person's arm and hand as they donate blood.
(Image: iStock/hxdbzxy)

For decades, LGBTQ+ patients have faced stringent requirements to donate blood—most gay and bisexual men were not allowed to donate at all. Now, however, many more of them will be able to give this selfless gift. The U.S. Food and Drug Administration, which regulates blood donation in this country, has reworked the donor-screening criteria, and in the process opened the door to donation for more Americans.

The previous restriction on accepting blood from men who have sex with men (MSM) dates back to the early days of the AIDS epidemic, when blood donations weren’t able to be screened for HIV, leading to cases of transfusion-transmitted HIV. In 1985, the FDA instituted a lifetime ban on blood donation for MSM, effectively preventing gay and bisexual men from donating. (Also included were women who have sex with MSM.)

Twenty years later, the agency rescinded the ban—but added a restriction that only MSM who had been abstinent from sex for at least one year could donate. In 2020, the FDA shortened the “deferral” period to 90 days of abstinence. While the changes were welcome news for those who had been unable to donate, they still prevented many MSM from giving blood. As he wrote in an op-ed for the Philadelphia Inquirer last year, Kevin B. Johnson, the David L. Cohen University Professor with appointments in the School of Engineering and Applied Science, the Perelman School of Medicine, and Annenberg School for Communication, was one of them. He and his husband were shocked to learn when they went to donate blood during a shortage early in the COVID-19 pandemic, that despite being married and monogamous for close to 17 years, they could not donate unless they were celibate for three months.

“It is time to move quickly to a policy under which all donors are evaluated equally and fairly, and to encourage local blood collection facilities to comply with that policy,” Johnson wrote last year.

Now, such changes are underway. As the pandemic wound down, the FDA moved forward with plans to re-evaluate its donation criteria. The first big change was removal of an indefinite ban on people who lived in or spent significant amounts of time in the United Kingdom, Ireland, and France, a measure that aimed to protect the U.S. blood supply against Creutzfeldt-Jakob disease (CJD; also known as “mad cow disease”), a terminal brain condition caused by hard-to-detect prions that occurred in those countries in the 1980s and 1990s.

Extensive and careful evaluation of epidemiological studies and statistical analysis has shown that the risk of CJD transmission is no longer a concern. The changes to eligibility for LGBTQ+ patients are related to advances in medical and social science, and have also been very thoroughly studied to ensure that the changes will maintain the safety of the blood supply without being discriminatory.

“In the decades since HIV was first recognized, there have been advances in testing methods for detection of the virus, changes in how we process blood products, public health advances, and extensive study of the evolving risk of disease transmission given these advances,” says Sarah Nassau, vice chair of pathology and laboratory medicine at Lancaster General Hospital.

They also draw on rethinking the reliability of the guidelines. For example, while the rules partially or fully prevented gay and bisexual men from donating blood, they did not erect similar barriers to other people engaging in anal sex, or people who have multiple partners.

“Specifying the sexual orientation of the person rather than a behavior in which they engaged was discriminatory and not evidence based,” points out Judd David Flesch, vice chief of inpatient operations in the Department of Medicine at Penn Presbyterian Medical Center and co-director of the Penn Medicine Program for LGBT Health.

Read the full story in Penn Medicine News.

Kevin Johnson is the David L. Cohen University of Pennsylvania Professor in the Departments of Biostatistics, Epidemiology and Informatics and Computer and Information Science. As a Penn Integrates Knowlegde (PIK) University Professor, Johnson also holds appointments in the Departments of Bioengineering and Pediatrics, as well as in the Annenberg School of Communication.

Mustafa Mir Named HHMI Freeman Hrabowski Scholar

Mustafa Mir

Mustafa Mir, Assistant Professor of Cell and Developmental Biology in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group, was selected as one of Howard Hughes Medical Institute’s 31 new Freeman Hrabowski Scholars. The group consists of outstanding early career faculty in science who have potential to become leaders in their research fields and to create diverse and inclusive lab environments in which everyone can thrive. Mir and his lab develop and apply new microscopes to directly visualize the molecular scale events that underlie gene expression within live embryos.

Read a Q&A with Mir in the Children’s Hopsital of Philadelphia (CHOP)’s Cornerstone Blog: “New Technologies Lead to New Discoveries’: Q&A With HHMI Scholar Mustafa Mir, PhD.

This announcement originally appeared in Penn Medicine News.

2023 Department of Bioengineering Juneteenth Address: “A White Neighbor, a Black Surgeon, and a Mormon Computer Scientist Walk into a Bar…” (Kevin B. Johnson)

Kevin B. Johnson, MD, MS

We hope you will join us for the 2023 Department of Bioengineering Juneteenth Address by Dr. Kevin B. Johnson.

Date: Wednesday, June 14, 2023
Start Time: 11:00 AM ET
Location: Berger Auditorium (Skirkanich Hall basement room 013)

Zoom link
Meeting ID: 925 0325 6013
Passcode: 801060

Following the event, a limited number of box lunches will be available for in-person attendees. If you would like a box lunch, please RSVP here by Monday, June 12 so we can get an accurate headcount.

Speaker: Kevin B. Johnson, MD, MS, FAAP, FAMIA, FACMI
David L. Cohen University Professor
Annenberg School for Communication, Bioengineering, Biostatistics, Epidemiology and Informatics, Computer and Information Science, Pediatrics
VP for Applied Informatics (UPHS), University of Pennsylvania

Title: “A White Neighbor, a Black Surgeon, and a Mormon Computer Scientist Walk into a Bar…”

Abstract: As we recognize Juneteenth, a holiday that brings awareness to what journalist Corey Mitchell calls “…a complex understanding of the nation’s past”, we also need to understand how many of our neighbors, staff, and faculty—even those born in the last 100 years—continue to navigate through the environment that made Juneteenth remarkable. Dr. Johnson will share a bit of his personal story and how this story informs his national service and passion for teaching.

Bio: Dr. Johnson is a leader of medical information technologies to improve patient care and safety. He is well regarded and widely known for pioneering discoveries in clinical informatics, leading to advances in data acquisition, medication management, and information aggregation in medical settings.

He is a board-certified pediatrician who has aligned the powers of medicine, engineering and technology to improve the health of individuals and communities. In work that bridges biomedical informatics, bioengineering and computer science, he has championed the development and implementation of clinical information systems and artificial intelligence to drive medical research. He has encouraged the effective use of technology at the bedside, and he has empowered patients to use new tools that help them to understand how medications and supplements may affect their health. He is interested in using advanced technologies such as smart devices and in developing computer-based documentation systems for the point of care. He also is an emerging champion of the use of digital media to enhance science communication, with a successful feature-length documentary describing health information exchange, a podcast (Informatics in the Round) and most recently, a children’s book series aimed at STEM education featuring scientists underrepresented in healthcare.

Dr. Johnson holds joint appointments in the Department of Computer and Information Science of the School of Engineering and Applied Science, and secondary appointments in Bioengineering and the Annenberg School for Communication. He serves as Vice President for Applied Informatics in the University of Pennsylvania Health System and as a Professor of Pediatrics at the Children’s Hospital of Philadelphia.

Before arriving at Penn, he served as the Cornelius Vanderbilt Professor and Chair of the Department of Biomedical Informatics at the Vanderbilt University School of Medicine, where he had taught since 2002. As Senior Vice President for Health Information Technology at the Vanderbilt University Medical Center, he led the development of clinical systems that enabled doctors to make better treatment and care decisions for individual patients, and introduced new systems to integrate artificial intelligence into patient care workflows.

The author of more than 150 publications, Dr. Johnson has held numerous leadership positions in the American Medical Informatics Association and the American Academy of Pediatrics. He leads the American Board of Pediatrics Informatics Advisory Committee, directs the Board of Scientific Counselors of the National Library of Medicine, and is a member of the NIH Council of Councils. He is an elected member of the National Academy of Medicine, American College of Medical Informatics and Academic Pediatric Society. He has received awards from the Robert Wood Johnson Foundation and American Academy of Pediatrics, among many others.

Penn Bioengineering Graduate Student on T Cell Therapy Improvements

Image: Courtesy of Penn Medicine News

 Neil Sheppard,  Adjunct Associate Professor of Pathology and Laboratory Medicine in the Perelman School of Medicine, and David Mai, a Bioengineering graduate student in the School of Engineering and Applied Science, explained the findings of their recent study, which offered a potential strategy to improve T cell therapy in solid tumors, to the European biotech news website Labiotech.

Mai is a graduate student in the lab of Carl H. June, the Richard W. Vague Professor in Immunotherapy in Penn Medicine, Director of the Center for Cellular Immunotherapies (CCI) at the Abramson Cancer Center, and member of the Penn Bioengineering Graduate Group.

Read “Immunotherapy in the fight against solid tumors” in Labiotech.

Read more about this collaborative study here.