Eric J. Rellinger, MD, FACS, a pediatric surgeon-scientist at the University of Kentucky in Lexington, has been selected to receive the 2026–2031 ACS George H. A. Clowes, MD, FACS, Memorial Career Development Award for his project, “Rewiring Glycosylation to Overcome Immunotherapy Resistance in High-Risk Neuroblastoma.”
Neuroblastoma is the most common extracranial solid tumor in children, and those diagnosed with high-risk disease face a 5-year survival rate of only about 50% despite aggressive multimodal treatment, including chemotherapy, radiation, stem cell transplantation, and immunotherapy. Dr. Rellinger’s research targets glycosylation, the post-translational addition of glycans to cell-surface proteins, as a novel and largely unexploited therapeutic axis for improving outcomes in this devastating disease.
His laboratory was the first to map the glycome of human neuroblastoma tumors in situ using matrix-assisted laser desorption ionization mass spectrometry imaging, identifying core fucosylation as a metabolic vulnerability enriched in MYCN-amplified tumors. MYCN amplification, present in nearly half of high-risk cases, drives upregulation of GDP-mannose 4,6-dehydratase (GMDS), the rate-limiting enzyme in de novo GDP-fucose biosynthesis. Genetic and pharmacologic disruption of this pathway impairs tumor growth in preclinical models.
The funded project investigates how aberrant core fucosylation helps tumors evade the immune system and reduces the effectiveness of existing immunotherapies. Dr. Rellinger has shown that core fucosylation regulates surface trafficking of the immune checkpoint proteins B7-H3 (CD276) and PVR (CD155), both of which suppress NK and T cell activity in the tumor microenvironment.
His central hypothesis is that blocking fucosylation will reprogram innate immune responses and enhance anti-GD2 immunotherapy. Although anti-GD2 immunotherapy improves survival in patients with high-risk neuroblastoma, its effectiveness against bulky tumors remains limited because NK cell–mediated antibody-dependent cellular cytotoxicity is often insufficient.
The project is organized around three specific aims:
- Using CRISPR-based loss-of-function models and lectin-based affinity proteomics to comprehensively define which cell-surface proteins depend on core fucosylation for their localization
- Characterizing how fucosylation blockade modulates NK cell activation, degranulation, cytokine production, and cytotoxicity in co-culture models with neuroblastoma cells
- Testing whether pharmacologic inhibition—using 2-fluorofucose or the selective GMDS inhibitor Fucotrim I—can sensitize large, treatment-refractory tumors to anti-GD2 therapy in the immunocompetent 9464D syngeneic model
Dr. Rellinger earned his medical degree at Vanderbilt University School of Medicine in Nashville, Tennessee, and completed general surgery residency at Vanderbilt University Medical Center followed by a pediatric surgery fellowship at Cincinnati Children’s Hospital Medical Center in Ohio. During residency, he devoted 3 years to a dedicated research fellowship in the laboratory of Dai H. Chung, MD, MBA, FACS, studying novel therapeutic strategies targeting N-MYC in neuroblastoma.
Since joining the faculty at the University of Kentucky in 2021, he has built an independent research program within the Markey Cancer Center.
The Clowes Award is supported through contributions to the ACS Foundation with funding from The Clowes Fund, Inc., of Indianapolis, Indiana. Its purpose is to help advance the research of a promising young surgical investigator. The award provides a stipend of $45,000 per year for 5 years and is not renewable.
More information is available at facs.org/clowes.
