CHOP Research Poster Day and Scientific Symposium: Investigating Pediatric Neuroscience

By Jillian Rose Lim, Lauren Ingeno, Kate Knab, Barbara Drosey, and Nancy McCann

Children’s Hospital of Philadelphia Research Institute’s annual Poster Day and Scientific Symposium expanded our understanding of pediatric neuroscience, from the study of genetic and environmental factors on brain development to novel therapies for rare neurological conditions. Read on for highlights of presentations from this year’s theme: “Neuroscience 2024: Mechanisms and Emerging Therapies for Brain Disorders of Childhood.”

Micro to Macro: Scaled Perspectives on Risks for Neurodevelopmental Disorders

Aaron Alexander-Bloch, MD, PhD, director of the Brain-Gene-Development Laboratory, chaired the opening session with talks ranging from perinatal environmental and genomic risk factors for neurodevelopmental disorders to larger-scale perspectives on brain development and behavioral markers for autism spectrum disorder. 

Attending physician in the Division of Neonatology Heather Burris, MD, MPH, focused on how on identifying population-level exposures – structural and environmental inequities related to neighborhoods, air, and water – play a significant role in early-life determinants of healthy brain development, such as full or preterm gestation.

“Where we live matters for our health, and there are disparities in exposure to air pollution across our country based on differences in zoning, who lives near highways, and who lives near industry,” Dr. Burris said. “When you pull studies, regardless of race or ethnicity, higher air pollution is associated with an 11% increased risk in preterm birth.”

Dr. Burris will continue to study lifespan data about environmental factors, such as pollution, extreme temperatures, neighborhood violence, and more, that affect children’s health before and after birth through a multisite, nationwide project called Penn-CHOP ECHO: the Environmental Influences on Child Health Outcomes.

Other presenters during the first session included:

• Michael Gandal, MD, PhD, an investigator in the Lifespan Brain Institute, shared his work in creating a large-scale isoform-centric and single-cell atlas of the developing human neocortex during mid-gestation by clustering cells based on isoform expression.

• Hao Huang, PhD, a senior scientist in the Department of Radiology, explained how he is part of the multisite HEALthy Brain and Child Development Study that uses novel neuroimaging and analysis to delineate human brain development from infancy, with the objective of helping researchers predict future behavior at 2 years old.

• Julia Parish-Morris, PhD, an investigator in the Center for Autism Research, explored infant vocalizations as early biobehavioral markers for autism that could contribute to earlier diagnosis and intervention.

The session ended with Keynote Speaker Joseph Gleeson, MD, Rady Professor of Neuroscience at the University of California San Diego, whose lab focuses on identifying genes associated with very early onset of neurodegenerative diseases. One research area his lab is studying is the underlying cause of meningomyelocele, or spina bifida, which is a result of a defect that prevents neural tubes from closing normally. By uncovering genes mutated in neural tube defects, Dr. Gleeson hopes to identify targets for individually designed therapeutic approaches.

Examining Genetic Origins of Neurological Conditions

Naiara Akizu, PhD, CHOP researcher and assistant professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania, chaired the second session of the day. She introduced the Scientific Symposium Co-chair Rebecca Ahrens-Nicklas, MD, PhD, co-leader of the Gene Therapy for Inherited Metabolic Disorders Program, sees rare metabolic diseases as pioneering conditions that can lead to the development of gene therapy treatments for these and other rare disorders.

In her presentation, “Optimizing Outcomes in Neurometabolic Disorders with Gene Therapy,” Dr. Ahrens-Nicklas pointed out that more than 80% of rare metabolic disorders affect the central nervous system.

“These diseases already have relevant, quantifiable biomarkers to aim for: There is a buildup of a toxin upstream, resulting in an insufficiency of a required molecule downstream,” said Dr. Ahrens-Nicklas, assistant professor of Pediatrics at Penn.

Dr. Ahrens-Nicklas illustrated her point with phenylketonuria (PKU), an inherited genetic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase, that affects liver function. An adeno-associated viral vector-based gene replacement is a possibility, but the transgene can become diluted as the patient grows.

“Targeting the liver to treat PKU with gene editing is more durable with the child’s growth,” Dr. Ahrens-Nicklas said. “The question is: How do we expand targeted gene editing beyond a single variant? Our work is ongoing in that area.”

Other presenters during the second session included:

• Kai Wang, PhD, a scientist in the Department of Biomedical and Health Informatics described how long-read sequencing is advantageous to short-read methods, as the technology captures 50% more data. This is especially useful when analyzing complex and repetitive regions longer than 350 base pairs.

• Xilma Ortiz-Gonzalez, MD, PhD, a physician-scientist and pediatric neurogeneticist who helped identify the novel disease gene TBCK, discussed the evolving comprehension of the “mighty mitochondria” in her talk on “Mitochondrial Dysfunction: A Common Denominator in Neurodevelopmental Disorders.”

• Ana G. Cristancho, MD, PhD, a child neurologist in the Division of Neurology, discussed the varied outcomes of prenatal hypoxia in “Disruptions of the Epigenetic Landscape from Prenatal Hypoxic Injury.”

Glia, Neurons, and Circuits

Chaired by F. Chris Bennett, MD, assistant professor of Psychiatry at Penn, Session III included a presentation by this year’s Scientific Symposium Co-chair Ethan Goldberg, MD, PhD, associate professor in the Division of Neurology and director of the Epilepsy Neurogenetics Initiative at CHOP. His talk focused on Dravet syndrome, a severe neurodevelopmental condition defined by treatment-resistant epilepsy and features related to autism spectrum disorder, due to genetic mutation in the gene SCN1A encoding the voltage-gated sodium channel subunit Nav1.1. 

The Goldberg Lab is redefining the understanding of how the loss of Nav1.1 impacts discrete cell types embedded within microcircuits of the neocortex, a theme that overlapped with the subject of brain cell type diversity discussed by Featured Speaker Hongkui Zeng, PhD, director of the Allen Institute for Brain Science.

“Understanding mechanisms of neurodevelopmental disorders from gene to neuron, circuit, and behavior, is critical toward novel therapeutic approaches for this class of childhood brain disease,” Dr. Goldberg said. “Work presented at the Poster Day and Scientific Symposium shows that CHOP is a leader in these efforts.”

Other CHOP speakers during the third session included:

• Neuroscientist Amelia Eisch, PhD, presented, “Learning From Mice: Parsing the Neural Circuitry Underlying the Memory of Similar Events.”

• Brian White, MD, PhD, of the Division of Cardiology, spoke about, “Optical Imaging of Functional Connectivity Networks as a Biomarker of Neurologic Injury.”

• Joseph Zackular, PhD, assistant professor of Pathology and Laboratory Medicine, discussed his lab’s findings that although C. difficile is asymptomatic in babies, it may not be immunologically silent. His talk was titled, “From Mechanism to Medicine: Bringing the Microbiome to Pediatrics.”

Emerging Therapies for Brain Disorders

The final Symposium session took a deep dive into emerging therapeutic approaches for pediatric brain disorders. CHOP clinician-scientists are developing gene therapies for Batten disease, editing metabolic genes in utero, designing clinical trials for a rare form of leukodystrophy, and harnessing microglia to treat neuroimmunological disease.

In the lab of Mariko Bennett, MD, PhD, researchers are studying the role of microglia in health and disease to identify new microglia-based therapies. Microglia — the resident immune cells of the brain and spinal cord — are essential for clearing out dead neurons during normal development and patrolling their environment for pathogens.

“Genome-wide association studies have revealed that many neurologic diseases, even classic neuron diseases like Alzheimer's disease, might be a microglia problem,” said Dr. Bennett, a neurologist and assistant professor of Neurology. “And mutations that are expressed exclusively or largely by microglia can confer risk and underlie these very general diseases. With all this in mind … microglia are the ideal neuro-therapeutic target.”

Other CHOP presenters during the final session included:

• Beverly L. Davidson, PhD, director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics and CHOP’s chief scientific strategy officer, described her lab’s decades of research developing an adeno-associated virus (AAV) gene therapy to treat Batten disease — a fatal genetic disorder that affects the body’s ability to get rid of cellular waste.

• William H. Peranteau, MD, an associate professor of Surgery, highlighted his lab’s investigations of in utero applications of cell and gene therapies, specifically to treat metabolic liver disease.

• Adeline L. Vanderver, MD, program director of the Leukodystrophy Center of Excellence, spotlighted her work with the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) to design clinical trials for TUBB4A-related leukodystrophy treatments.

Poster Sessions

There were two poster sessions at this year's event, one held on each day. 120 posters were presented across the two sessions, with a 30-year record high of 202 abstracts submitted for inclusion. Presenters were able to choose from a clinical, patient-oriented focus or laboratory-based research, judged separately based on scientific merit as well as the visual and oral presentation.

35 faculty and staff members judged the 120 poster presentations, with 20 winners selected from each of the two research tracks.

Additionally, six students from CHOP-RISES, an intensive internship program for traditionally under-represented high school students, presented at poster sessions. Ayobami Bidokwu was selected as the top presenter of CHOP-RISES presenters, judged by Francis Ayombil, PhD and Rodney Camire, PhD.

Flash Talks Fill Three Minutes with Fascinating Science

The 2024 Poster Day and Scientific Symposium also offered research trainees and research staff the opportunity to share their exciting discoveries with the CHOP community in engaging and interactive ways.

What does Spiderman have to do with neutrophil extracellular traps (NETs)? Why does less equal more when it comes to the protein tropomyosin 1 in blood cell production? How many biological clocks are really ticking away inside the body? These were just some of the catchy and creative analogies used by the six competitors, selected by a review committee out of submitted abstracts, in this year’s Science Slam Flash Talks May 1.

In just three minutes and one slide, the competitors explained the methodology and impact of one of their research projects. Audience members voted on their top two choices based on how each participant communicated their science and its impact. At the PDSS reception later in the day, the Audience Choice Prize winners, Veronica Bochenek and Evan Rosenberg, were announced alongside the 40 Poster Day Award winners. Congratulations to all the poster presenters!

Flash Talks with Internal Grant Awardees

Faculty members and other internal grant awardees also honed their savvy science communication skills at PDSS this year. Recipients of the Foerderer Award and the Omics Scalable Strategies Award, both internal grant programs at CHOP, presented their flash talks on April 30 to an audience composed of scientists, staff, and students.

• The Foerderer Award presenters included Casey Zampella, PhD, who shared how advanced tech tools could be used to analyze social cues more accurately in autism, leading to earlier diagnoses and interventions.

• Donald Joseph, PhD, spoke on his research in Friedreich’s Ataxia and the role that defective cell communication in the brain’s cerebellum might play in the disease’s progression.

• Barbara Chaiyachati, MD, PhD, described fascinating work on how experiences become “biologically embedded” into an individual’s health trajectory primarily through epigenetic mechanisms like methylation changes.

• Zhiqiang Sha, PhD, presented the complex connections between our brains, genes, and the world around us, and how their interactions can shape behavior, personality, and mental health.

• Benjamin Yerys, PhD, shared novel approaches to helping autistic youth transition from high school to adulthood that consider personal values and unique motivational strategies.

• Yuanquan Song, PhD, the Omics Scalable Strategies Award recipient, presented his research studying neural degeneration and regeneration as controlled by glia-neuron metabolism.

After the flash talks, audience members asked the presenters questions that prompted lively discussions on topics such as how to incorporate autism transition programs into clinical care and the future implications of research on epigenetic “clocks.” 

Special thanks go to the 2024 Poster Day and Scientific Symposium organizers: The Office of Faculty Development, the Office of Academic Training and Outreach Programs, and Scientific Symposium Co-chairs Drs. Ahrens-Nicklas and Goldberg.