Outstanding Science Award, Highly Cited Researcher, STAT Wunderkinds

 

In this week's news highlights, learn about a Children's Hospital of Philadelphia investigator who will be recognized for his considerable contribution to pediatric science. Find out which researchers are among the most highly cited, and who were named 2022 STAT Wunderkinds. Read about genetic variants linked to cancer risk in children with birth defects, and other variants associated with earlier onset childhood epilepsy. Round out your reading with a study on how acute myeloid leukemia ages immune cells.

Chris Feudtner, MD, PhD

Chris Feudtner, MD, PhD, MPH, Receives Norman J. Siegel Outstanding Science Award

The American Pediatric Society (APS) announced that Chris Feudtner, MD, PhD, MPH, is the recipient of the 2023 Norman J. Siegel New Member Outstanding Science Award. The award recognizes a new APS member for considerable contribution to pediatric science. Dr. Feudtner will accept the award at the Pediatric Academic Societies Annual Meeting in 2023.

Dr. Feudtner is the division chief of General Pediatrics and director of Research for the Justin Michael Ingerman Center for Palliative Care at CHOP. Dr. Feudtner also holds the Steven D. Handler Endowed Chair in Medical Ethics and is a core faculty member of Clinical Futures, a CHOP Research Institute Center of Emphasis. He is a leader in research for pediatric palliative care, children with medical complexity, and pediatric medical ethics. He cofounded CHOP's first pediatric palliative care team in 2003 and launched CHOP's Department of Medical Ethics.

Stephan Grupp, MD, PhD

Two CHOP Investigators Named to Clarivate's Highly Cited Researchers List

Stephan Grupp, MD, PhD, and Kyle Bittinger, PhD, appear on the 2022 Clarivate Highly Cited Researchers list. The list identifies global research scientists and social scientists with exceptional influence, demonstrated through their publication of many papers often cited by their peers.

Dr. Grupp is director of translational research at the Center for Childhood Cancer Research, director of the Cancer Immunotherapy Frontier Program, chief of the Cellular Therapy and Transplant Section, and professor of Pediatrics at Penn. Dr. Grupp's research focuses on the development of targeted and cell therapies and the study of molecular signaling pathways in acute lymphoblastic leukemia. He is a pioneer in the field of pediatric CAR T-cell therapy.

Dr. Bittinger is analytical core director at CHOP Microbiome Center, a group committed to collaborative research that develops bioinformatics approaches to enhance the level of insight gained from clinical studies that come through the Center.

"This (recognition) reflects the active community of human microbiome researchers at Penn and CHOP, and CHOP's robust support for the CHOP Microbiome Center," said Dr. Bittinger, who also is assistant professor of Pediatrics at the University of Pennsylvania. "Moving forward, we're working to predict how the human microbiome responds to antibiotic intervention and to measure how the gut microbiome works as a factory for metabolites that impact human health."

Next Generation Scientists Selected as 2022 STAT Wunderkinds

The health and science news outlet STAT selected two CHOP researchers as 2022 Wunderkinds in recognition of the next generation of scientists who are making significant contributions to biomedical research.

Caroline Diorio, MD, a fellow in the Cancer Center, focuses her research on immunotherapy for pediatric T-cell acute lymphoblastic leukemia (T-ALL). Specifically, she is evaluating a gene-editing tool called cytosine base editing to create CAR-T therapy for patients with T-ALL. In her profile on STAT, Dr. Diorio noted the therapy led to better genomic stability and better cell proliferation than CAR-T cells made with CRISPR-Cas9, and the cells were active against T-ALL in animal models.

Alexander Tucker, MD, an attending neurosurgeon in the Division of Neurosurgery, conducts research in the field of wound healing. He works with a material scientist at Penn on an adhesive specifically designed to leave minimal scarring on children's heads and faces. In Dr. Tucker's STAT profile, he shared how his work is informed by his patients' desire to heal without a scar.

Hakon Hakonarson, MD, PhD

Critical Step for Earlier Detection of Cancer in Children With Birth Defects

Researchers led by Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at CHOP, identified several genetic variants that are associated with increased risk of cancer in children with non-chromosomal birth defects.

Children with non-chromosomal birth defects are up to 2.5 more times likely to be diagnosed with cancer than children without birth defects. To identify potential genetic mechanisms for this risk, the researchers evaluated data from whole genome sequencing of blood samples from 1,653 individuals without chromosomal abnormalities. The samples included 541 birth defect probands with malignant tumors, 767 birth defect probands without malignant tumors, and 345 healthy family members.

While the study identified thousands of variants of interest, five genes in particular – AXIN2, BMP1, CR1, ERBB2, and RYR1 – are associated with birth defects and the increased risk of cancer. In a subsequent deep learning model to assess the variants of interests, the validation samples achieved 75% accuracy.

"While more research is needed to delve into the variants of interest we identified, this study represents a critical step toward the earlier detection of cancer in children with non-chromosomal birth defects," Dr. Hakonarson said.

The findings appear in the journal Biomarker Research. Find out more in the CHOP press release.

Gain-of-Function Variant Linked to Earlier Onset Childhood Epilepsy

CHOP researchers found that a genetic variant in SCN1A, the most common genetic epilepsy, appears to lead to an earlier onset of epilepsy and has clinical features that differ from other epilepsies. The study authors from the Epilepsy Neurogenetics Initiative (ENGIN) also identified a potential treatment strategy.

Most genetic variants of SCN1A are loss-of-function variants associated with Dravet syndrome. This study focused on a gain-of-function variant. Researchers identified four patients with the gain-of-function variant, all of whom had early-onset developmental and epileptic encephalopathy. The study found that patients with this variant had earlier onset of their disease compared with patients with loss-of-function variants. In addition, researchers found the variant may be sensitive to oxcarbazepine.

"Our findings may provide an explanation for why we had previously diagnosed some patients as having atypical Dravet Syndrome, as the earlier onset of symptoms associated with this gain-of-function variant allow us to properly distinguish these cases," said Jérôme Clatot, PhD, first author on the study and director of the ENGIN Ion Channel/Electrophysiology Core at CHOP. "We hope to raise awareness of this and other potential gain-of-function variants, particularly if common anti-seizure medications may be able to help them."

The findings appear in the journal Epilepsia. Read more in the CHOP press release.

Acute Myeloid Leukemia Ages Immune Cells, Impairs Treatment Response

An international group of researchers including Sarah K. Tasian, MD, chief of the Hematologic Malignancies Program at CHOP and associate professor of Pediatrics at Penn, reported that acute myeloid leukemia (AML) ages immune cells and impairs their ability to fight off the cancer. Patients with more of these aged cells had worse responses to chemotherapy and immunotherapy, and lower overall survival.

Researchers studied tumor samples from nearly 2,000 patients with AML and identified a genetic signature of immune dysfunction in these patients that is characterized by T cell aging and exhaustion. Patients who had these highly exhausted T cells had a worse response to chemotherapy than those with lower levels of T cell dysfunction. These patients were also less likely to respond to immunotherapy.

"These findings have important implications for the treatment of children, adolescents, and adults with AML, particularly when it comes to identifying patients who might respond successfully to immunotherapy," Dr. Tasian said. "Future research will endeavor to identify ways of reinvigorating aging and exhausted immune cells in patients with AML, which could lead to more successful treatment."

The findings appear in the Journal of Clinical Investigation. Learn more in the CHOP press release.

ICYMI

Catch up on our headlines from our Nov. 25 In the News:

• Amber Zimmerman, PhD, Wins Philadelphia Marathon
• Adolescent Mental Health Affected by Financial Strain of COVID-19
• Study Shows Antibiotic-Resistant Microbes in Gut Make C. Difficile More Infectious
• CHOP Team Ties for First in Machine-Learning Natural Language Processing Challenge
• Research Shows Liquid Biopsies Catch Disease Progression Early in High-risk Neuroblastoma

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