Neuroblastoma Targets, Pediatric Scientist Development Program, Genetic Epilepsy

 

Discover new targets for chemotherapy-resistant neuroblastoma identified by Children's Hospital of Philadelphia researchers, and meet two fellows who earned spots in the Pediatric Scientist Development Program. Two physician-scientists also received an award from Blood Cancer Discovery for most outstanding article. Catch up on these research highlights and more:

Potential New Targets Identified for Chemotherapy-resistant Neuroblastoma

For the first time, researchers have identified malignant cells responsible for relapse in neuroblastoma in a new study published in Cancer Discovery. The findings offer valuable insight into potential new therapeutic targets for treating chemotherapy-resistant high-risk neuroblastoma.

"This study is a major step forward in identifying why neuroblastoma is so difficult to cure," said John Maris, MD, study co-author and pediatric oncologist who also holds the Giulio D'Angio Chair in Neuroblastoma Research. "Targeting specific cells and pathways responsible for relapse empowers us to chart a new path forward, allowing us to develop potentially safe and effective treatments for children and families battling this aggressive cancer."

This study leveraged a multi-omics dataset generated by the Human Tumor Atlas Network (HTAN), a National Cancer Institute (NCI) Moonshot initiative led by Kai Tan, PhD, an investigator in the Center for Childhood Cancer Research at CHOP. The CHOP research team used advanced single nucleus RNA sequencing and bulk whole genome sequencing to analyze the genetic and transcriptional profiles of tumor samples from 20 pediatric patients with high-risk neuroblastoma.

The investigators discovered that neuroblastoma can evade chemotherapy by lying dormant and not actively multiplying. These "persister" cells can hide in the body for months or years and eventually lead to relapse. Dr. Maris noted that ongoing NCI-funded neuroblastoma research is actively pursuing several immunotherapeutic strategies to eliminate persister cells.

Learn more in this CHOP news brief.

Two CHOP Fellows Join Pediatric Scientist Development Program Cohort

The Pediatric Scientist Development Program (PSDP) is a National Institutes of Health K12 program that provides extensive training in research relevant to specialty areas of pediatrics for entry-level faculty to help prepare them for successful research careers in basic, translational, clinical, or health services research.

PSDP selected two CHOP fellows to participate in their 2025 cohort: Jon Ghergurovich, MD, PhD, in the Department of Pediatrics, and Sarah McCuaig, MD, DPhil, in the Division of Rheumatology.

"I'm thrilled to have been selected as part of the 2025 PSDP cohort," Dr. Ghergurovich said. "The PSDP has an exceptional track record of supporting aspiring physician-scientists in Pediatrics, and I look forward to accessing the resources and mentorship opportunities associated with this award to study the role of T-cell exhaustion in pediatric cancers."

"I am incredibly grateful for the protected time and financial support the PSDP Award provides to fuel my research," Dr. McCuaig said. "Moreover, I feel honored and privileged to join and to learn from this wonderful community of pediatric physician scientists."

PSDP provides three years of training for pediatricians, with funding support through each year of professional development. External mentorship is offered through their alumni mentorship program to residents interested in a PSDP fellowship opportunity. Ninety-two percent of program graduates go on to work in academic pediatrics, including Chair of the Department of Pediatrics at CHOP, Joseph St. Geme, MD.

Congratulations to Dr. Ghergurovich and Dr. McCuaig!

AI-powered Strategy Could Offer Earlier Diagnosis, Treatment of Genetic Epilepsies

A new study conducted by researchers of the Epilepsy Genetics Initiative (ENGIN) used machine learning and artificial intelligence to scan electronic health records and clinical notes to match symptoms with specific genetic epilepsies. This strategy could greatly decrease the time between diagnosis and treatment, improving patients' quality of life and care.

"By examining a very large dataset of individuals with childhood epilepsies, we believe that our results could be used prospectively for new diagnoses," said senior study author Ingo Helbig, MD, core faculty member of ENGIN, and clinical director of the CHOP/Penn Center for Epilepsy and Neurodevelopmental Disorders. "In the era of precision medicine, quicker, more accurate prognoses could make an enormous difference in the lives of individuals living with genetic epilepsies."

Using Natural Language Processing, an AI-driven standardized method for processing clinical information from text in electronic health records, researchers extracted 89 million timestamped clinical annotations from more than 4 million clinical notes on 32,112 individuals with childhood epilepsy; 1,925 individuals had known or presumed genetic epilepsies. In total, researchers identified 710 genetic etiologies, noting that a wide range of genetic epilepsies have key clinical features that present prior to genetic testing and diagnosis.

The study appears in Genetics in Medicine. Learn more in this CHOP news brief.

Washington Post Highlights Undiagnosed Disease Program

An article from the Washington Post highlighted CHOP's Undiagnosed Disease Program (UDP), which operates as one of 15 academic medical centers under the Undiagnosed Diseases Network (UDN) with funding from the National Institutes of Health. Over the last several years, CHOP, along with other institutions in the UDN, has helped diagnose more than 750 patients and identify 60 new disorders.

"We have expanded from serving 30 patients in 2023 to be on course to seeing 200 patients this year," Kathleen Sullivan, MD, PhD, director of the UDP, said in the Post article. "We're really proud that we're enrolling new patients every day."

The UDP helps patients like Luna Holt, who was diagnosed with Kagami-Ogata syndrome, and their families who are struggling to find a cause for their child's symptoms. Patients who are accepted into the program meet with a diverse team of physicians, including geneticists, neurologists, immunologists, orthopedic surgeons, and genetic counselors. They combine expertise with CHOP's extensive resources for genetic testing, such as whole exome sequencing, to potentially help identify a rare disease and alleviate the stress that comes with uncertain diagnoses.

"Diagnosis is often the path towards optimized treatment," said Dr. Sullivan, who is also Luna's immunologist. "The multidisciplinary team maximizes technology and old-fashioned know-how to find the answers for our patients."

CHOP Researchers Receive 2024 Blood Cancer Discovery Award

The downregulation of surface proteins that help the body trigger immune responses can contribute to resistance to immunotherapy in B-lymphoblastic leukemia (B-ALL), according to two CHOP researchers recently awarded the 2024 Blood Cancer Discovery Award for Outstanding Journal Article from Blood Cancer Discovery.

Blood Cancer Discovery, a journal of the American Association for Cancer Research, and its editor Robert Kruger, PhD, awarded CHOP researchers Sarah Tasian, MD, and Andrei Thomas-Tikhonenko, PhD, with this award for their work, "Modulation of CD22 Protein Expression in Childhood Leukemia by Pervasive Splicing Aberrations: Implications for CD22-Directed Immunotherapies."

Unlike CD19, a widely targeted protein in immunotherapy that develops resistance by "turning off" so cells are CD19 negative, CD22 expression merely "dims," and could still be detectable.

Dr. Tasian and Dr. Thomas-Tikhonenko sat down with Dr. Kruger in an interview to dive deeper into their work exploring different avenues for immunotherapy-resistant leukemia.

"Targeting CD22 has been a little bit trickier just because of the heterogeneous expression," Dr. Tasian said. "We know there are some subtypes of ALL that have dim CD22 expression, so if there are biologic or mechanistic modalities to try to increase that cell surface density, that may make some of these therapeutics more effective in future clinical testing."

Congratulations to Drs. Tikhonenko and Tasian!

Watch the full interview to learn more.

PolicyLab Launches 4th Annual Impact Report

PolicyLab, a Research Institute Center of Emphasis, celebrated its hard work informing programming and policy changes through interdisciplinary research over the course of this past fiscal year with the release of its fourth annual Impact Report.

"This dynamic report illustrates our [PolicyLab] model in action," said PolicyLab Director, Meredith Matone, DrPH, in the introductory video. "Researchers, paired with policy and communications experts, work together towards our vision of all children, teens, and caregivers being their healthiest selves."

As a core pillar of PolicyLab, the community engagement section of the report spotlights their Community Partnerships in Research Program and the ways in which team members are actively involved in their communities to encourage and inspire future generations of researchers.

In this year's report, meet the researchers leading innovative pediatric research studies that have long-lasting, positive implications for the surrounding community, and learn more about the collaborative efforts that make these discoveries possible. Highlights include research on suicide prevention and the future of equity in telehealth.

ICYMI

Catch up on our headlines from our Aug. 2 In The News:

• David Teachey, MD, Appointed Chair of Children's Oncology Group ALL Disease Committee
• Researchers Examine Neighborhoods, Psychosocial Risk Factors, and Mental Health
• Single Cell Kidney Atlas that Sheds Light on CKD Progression
• Implementation of Virtual Driving Assessment in Primary Care Continues to Grow
• Researchers Develop Method to Re-characterize Variants Implicated in Alagille Syndrome
• Antibiotic Use in Extremely Low Birth Weight Infants Decreased Over Time

Keep up with our news, stories, and updates in real time by following us on X, Facebook, LinkedIn, or Instagram. Meet the minds behind the science in the Bench to Bedside podcast. Or subscribe to our newsletter to receive an email every other Friday.