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CHOP Research Poster Day and Scientific Symposium: Making the Microbiome Less Mysterious
By Jillian Rose Lim, Lauren Ingeno, Kate Knab, and Nancy McCann
From the miniscule communities of microbes inside our bodies to viral infections like Rubella, all manners of bugs and breakthroughs brought faculty, staff, and trainees together for the 2023 CHOP Research Poster Day and Scientific Symposium.
The two-day celebration, themed "Bugs and Breakthroughs: Through the Lens of the Microbiome," included speakers from Children's Hospital of Philadelphia and the University of Pennsylvania research community, as well as poster presentations and dynamic opportunities for attendees to network and socialize. The event held at the Hub for Clinical Collaboration also commemorated 100 years since the first research lab opened at CHOP.
"That 100 years has been framed by two major 'bugs,' the influenza pandemic in 1918-1919 and COVID-19 pandemic," said Susan Furth, MD, PhD, Executive Vice President and Chief Scientific Officer, in her introductory remarks. "Many of the transformative discoveries that have happened here at CHOP have centered on understanding, diagnosing, treating, and preventing some of the major infectious diseases in childhood — vaccines for polio, influenza, rabies, rubella, rotavirus, all have their roots here."
Symposium co-chairs Michael Silverman, MD, PhD, and Joseph Zackular, PhD, joined Dr. Furth in welcoming attendees.
"It has been a delight to put together these two days of microbiome research," said Dr. Zackular, a recipient of CHOP's Klaus Hummeler High-Impact Publication Award. "CHOP is a true leader in the space, and we are excited to showcase what's going on here on campus."
Keeping the Germs Away
Sagori Mukhopadhyay, MD, MMSc, assistant professor of Pediatrics at the University of Pennsylvania, chaired the symposium's opening session.
When Stanley Alan Plotkin, MD, was a medical resident in London in 1962, he was among the first to see patients with congenital rubella syndrome, which was sweeping across the United Kingdom. During the symposium, Dr. Plotkin, emeritus professor at the University of Pennsylvania, recounted his controversial decision to use fetal cells to create a rubella vaccine, which has since eradicated the disease from the United States.
"We want to eradicate disease from the world, which has only been done with one disease so far," he said. "I think rubella is definitely a candidate with vaccination."
Brendan J. Kelly, MD, MS, an assistant professor in the Penn Perelman School of Medicine, is investigating in a clinical trial whether fecal microbiota transplant can be used to "keep the germs away" from patients in a hospital environment without driving antibiotic resistance.
"The more antibiotics you get, you are less likely to move bacteria from your body to the environment," Dr. Kelly told the symposium audience. "But the reverse is also true: The more antibiotics, the more likely you are primed to take up bacteria from your environment."
Carolyn McGann, MD, an attending neonatologist at CHOP, is also studying multidrug-resistant bacteria in hospitals, which is a major cause of sepsis in newborns throughout the world.
"The neonatal intensive care unit is an interesting place to study these dynamics, because the typical interactions between mothers and babies that would allow for early seeding with a healthy microbiome are often interrupted," Dr. McGann said. "And instead, babies come into contact with healthcare workers like me, whatever is on my hands, the hospital environment, and a lot of antibiotics."
Through the Botswana-UPenn Partnership and the CHOP Global Health Center, and with support from CHOP's Foerderer Fund for Excellence, Dr. McGann and colleagues studied a cohort of nearly 500 newborns who were hospitalized in a NICU in Botswana. Through skin and nasal swabs, and DNA sequencing, they examined both the maternal and neonate microbiomes in order to understand how it affected sepsis risk. The research group's sequencing work is ongoing.
"My hope is that understanding risk factors for colonization with sepsis-causing pathogens may allow us to interrupt it," she said.
During the session's closing presentation, Alexander B. Smith, a graduate student in Dr. Zackular's lab, described his work investigating how microbial cooperation enhances the pathogenesis of Clostridioides difficile. His research suggests that the enterococci—an expansion of a group of antibiotic-resistant, opportunistic pathogens in the gut—reshape the microbiotic environment to enhance the fitness and pathogenesis of C. difficile.
Regulation and Modification of Microbiota
Dr. Silverman of the Division of Infectious Diseases at CHOP and assistant professor of Pediatrics at the University of Pennsylvania, chaired a session in which speakers examined the ways regulating and modifying the microbiome may treat dysbiosis, an imbalance of microbes in the gut that affects the body's susceptibility to certain diseases.
Highlights included a presentation by Lindsey Albenberg, DO, attending physician in Center for Pediatric Inflammatory Bowel Disease, whose research focused on how dysbiotic microbes affect the development of inflammatory bowel disease (IBD). Current treatment options under investigation include immunosuppression therapies.
"Our gold standard for the treatment of IBD is achieving histologic and endoscopic remission, and this happens in clinical trials only about 15% of the time," Dr. Albenberg said. "It's time for a microbiota 'makeover' in IBD either as primary therapy or adjunctive therapy."
In a phase 2 placebo controlled clinical trial called the Holiday study led by Dr. Albenberg and other CHOP researchers, treating patients with a combination of antibiotics normally used to treat refractory IBD, in conjunction with bowel lavage, or a purge of the bowels, resulted in decreased disease activity and fecal calprotectin, an indicator of inflammation in the gastrointestinal tract.
Additional featured speakers included Caitlin Elgarten, MD, MSCE, an attending physician with the Cancer Center, who focused on how dysbiotic microbiota following transplant surgery can result in worse outcomes. Jorge Henao-Mejia, MD, PhD, associate professor of Pathology and Laboratory Medicine at the Penn Perelman School of Medicine, examined how microRNA families affect the signaling pathways of the microbiome to protect against or contribute to inflammatory diseases. And Jean-Bernard Lubin, PhD, an academic diversity fellow, elaborated on the importance of microbial changes during weaning to promote immune system development.
Day one keynote speaker Mariana X. Byndloss, DVM, PhD, assistant professor of Pathology, Microbiology, and Immunology at Vanderbilt University, discussed her lab's work on how environmental factors such as diet may interact with the gut microbiome to prevent and cause complex diseases like obesity and cancer.
"Twenty percent of school age children in the United States are obese," Dr. Byndloss said. "Kids may be exposed to more than one risk factor at the same time, so we started with the simple question of what happens when we expose individuals to diet and antibiotics simultaneously."
Based on previous disease models, high fat diets lead to loss of epithelial cells and more inflammation, inducing mitochondrial dysfunction that results in an increase in oxygen and nitrate that produce metabolites responsible for heart disease and other health issues. Combining these high fat diets with antibiotics, her lab's models demonstrated faster weight gain, higher glucose levels, and lipid accumulation in the liver, all of which drive obesity in children.
Michael A. Fischbach, PHD, delivered the second keynote presentation of the event. The associate professor in the Department of Bioengineering Department of Microbiology and Immunology at Stanford University shared insights into understanding and manipulating immune modulation by the microbiome.
Early Life and the Microbiome
Investigator Kathryn Hamilton, PhD, led the Scientific Symposium session focused on early life and microbiome research at the Research Institute. One of the presenters, Naomi Butler Tjaden, MD, PhD, a third-year fellow with the Division of Gastroenterology, Hepatology and Nutrition, investigates Hirschsprung-associated enterocolitis (HAEC), which can lead to sepsis and is the greatest cause of morbidity and mortality in children with Hirschsprung disease, a congenital absence of nerves in the colon that prevents the passing of stool, causing dysmotility and constipation.
Building on the knowledge that diet affects microbial populations and microbes can influence motility and immune function, Dr. Tjaden's research goal is to learn what could be added to the diet of patients with HAEC to improve survival or gastrointestinal health. By comparing two diets in a Hirschsprung disease and HAEC disease model, her team discovered early death correlated with increased Enterobacteriaceae, a pathogenetic bacteria. In pre-clinical research, they demonstrated that adding tungstate to drinking water improved survival in a laboratory model by decreasing Enterobacteriaceae.
Sagori Mukhopadhyay, MD, MMSc, attending neonatologist at CHOP, and assistant professor of Pediatrics at Penn, spoke about preterm microbiome assembly and the implications of early antibiotic use in preterm infants with early onset sepsis.
Shaon Sengupta, MBBS, MPH, a neonatologist and physician scientist who studies lung health, demonstrated in her presentation, "Let the Clocks Talk: Circadian Regulation of Lung Inflammation and Repair," how circadian rhythms are relevant not just for regulating acute inflammation but also affect processes such as repair and regeneration.
Jeffrey S. Gerber, MD, PhD, chief clinical research officer, associate professor of Pediatrics and Epidemiology, and the Werner and Gertrude Henle Endowed Chair in Pediatrics, focused on how early life antibiotic use could change the structure and function of the developing gut microbiome in ways that affect health. He stressed the importance of antimicrobial or antibiotic stewardship: "We use too many antibiotics and need to define their long-term adverse effects," he said.
Bioinformatics for the Microbiome
Session IV chair Kyle Bittinger, PhD, director of the Analytical Core of the PennCHOP Microbiome Program, and assistant professor of Pediatrics, opened the session with his talk “Quantifying and Predicting the Human Microbiome Response to Antibiotics.” With his bioinformatics expertise, Dr. Bittinger plans to bring to the microbiome “predictive models that sit close to the experiment and encompass the way that we as humans think about how bacteria should be handled.” Working with data from infants who are suspected of having or who have bacterial infections, he is optimistic about making progress.
“We have a real shot at changing a little bit of the way doctors think about giving antibiotics and how they affect the gut at this critical stage of life,” Dr. Bittinger said.
Additional speakers during the final session included Ceylan Tanes, PhD, a bioinformatics scientist in the Analytical Core of the PennCHOP Microbiome Program, presented new analytical approaches to enhance 16S rRNA marker gene sequencing and Ahmed Moustafa, BPharm, PhD, the Sequencing Core director of PennCHOP Microbiome Center, and assistant professor of Pediatrics, who talked about “Alignment-free Recombination Detection Using Genomic Database Distributions of Exact Protein Matches.”
Robert Baldassano, MD, Colman Family Endowed Chair in Pediatric Inflammatory Bowel Disease and director of the CHOP Microbiome Center, rounded out the session with a summary of the microbiome program: past, present, and future. Highlights included how, since the launch of the program in 2015, the Center had completed 438 projects, collaborated with 163 PIs, and worked with 44 academic institutions by 2022. The future vision entails personalized microbiome-based medicine at CHOP. With a patient’s personalized microbiome and pathogen sequencing, along with the integration of predictive microbiome data and pathogen surveillance into clinical charts, healthcare providers will be able to make informed clinical decisions for drug treatment, diagnosis, and infection prevention.
Science… in a Flash
Flash Talks provided an opportunity for up-and-coming investigators chosen by the Symposium Committee to present key findings from their work using only a few minutes and a single slide.
Julia Rood, MD, PhD, a fellow in the Division of Rheumatology at CHOP, offered quick insights into mRNA vaccine immunobiology. While mRNA vaccines elicit robust response of CD4+ T cells, the sources of vaccine antigen responsible for effective T cell priming are unknown. Working with an mRNA vaccine immunization model, Dr. Rood and colleagues examined the relative contribution of exogenous and endogenous antigen presentation. Their findings suggested that endogenous antigen from antigen-presenting cells largely drive CD4+ T cell activation by mRNA vaccines. The findings, Dr. Rood said, could inform future vaccine development. Dr. Rood's work is supported by a Clinical Fellow/Instructor K-Readiness Pilot Grant Program grant.
Scott Daniel, PhD, a bioinformatics scientist in the CHOP Microbiome Center Core, presented results from two studies that sought to characterize the microbial and metabolic consequences of ileal resection, the most common surgery for Crohn's disease. Using shotgun metagenomics sequencing to analyze stool samples of patients with and without intestinal resection, the study team found the surgery was associated with altered fecal microbiome, increased primary bile acids, and reduced secondary bile acids.
Among those presenting lightning-fast science were the 2023 Distinguished Research Trainees.
Chief Scientific Strategy Officer Beverly L. Davidson, PhD, introduced the Distinguished Research Trainee Award recipients, including her own mentee, Ashley Robbins, a graduate student in the University of Pennsylvania Neuroscience Graduate Group. She was joined by fellow awardees Christopher Gaw, MD, MBE, a physician fellow in the Division of Emergency Medicine; Emma Sartin, PhD, MPH, a postdoctoral fellow in the Center for Injury Research and Prevention; and K. Taylor Wild, MD, a physician fellow in the Divisions of Neonatal-Perinatal Medicine and Medical Genetics and Genomics.
Posters, Presentations, and Prizes
Alongside its 100th anniversary, this year marked the Research Institute's 30th Poster Day, a visually impressive event where CHOP and Penn researchers dusted off their best elevator pitches and presentation skills for the opportunity to network, learn, and win awards.
On May 2 and 3, posters filled the lobby of the Ruth M. Colket Translational Research Center as the researchers presented on topics ranging from allergy and immunology to behavioral development and genetics and much more. Diva De Leon Crutchlow, MD, MSCE, acted as the lead for posters in the patient-oriented track, while Evan Weber, PhD, took on the role as the lead for posters in the lab-based track. After being evaluated on the scientific merit of their research, the quality of their poster, and the strength of their oral presentation, 20 researchers from the patient-oriented track and 20 from the lab-based track each received a $250 cash prize. See the full list of the winners from each track.
But CHOP and Penn individuals weren't the only ones to present in front of a captive audience at Poster Day.
A highlight of the final day were poster presentations by high school seniors Dayvontre Ferguson Epps and Ashley Rodriguez, participants in the CHOP Research Internship for Scholars and Emerging Scientists program. The comprehensive summer internship provides high school students opportunities and experience in science, technology, engineering, math, and medicine. Epps contributed to an abstract on continuous EEG monitoring for neonatal seizures, and Rodriquez's work focused on a case study of behavioral parent training in primary care for attention-deficit/hyperactivity disorder. Both are headed to college in the fall.