Kevin Huang

Program: Cancer Biology

Current advisor: Angela Hirbe, MD, PhD

Undergraduate university: University of Pennsylvania, 2024

Enrollment year: 2024

Research summary
Fueling Chromatin: Understanding and Targeting Metabolic Reprogramming in PRC2-Deficient Malignant Peripheral Nerve Sheath Tumors

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with limited treatment options and poor clinical outcomes. Loss of Polycomb Repressive Complex 2 (PRC2), a defining molecular alteration in MPNST, drives widespread epigenetic reprogramming, yet its metabolic consequences remain poorly understood. We are investigating how PRC2 deficiency rewires acetyl-CoA and lipid metabolism to support tumor growth and survival. Integrative transcriptomic and proteomic analyses reveal metabolic remodeling with altered lipid transport and fatty acid handling pathways, suggesting adaptation of programs that sustain acetyl-CoA-dependent chromatin regulation. We hypothesize these changes create targetable metabolic vulnerabilities. To test this, we evaluate inhibition of ATP citrate lyase (ACLY), a key enzyme linking central carbon metabolism to acetyl-CoA production, using the FDA-approved drug bempedoic acid alongside other small molecule chemotherapeutics. Preliminary studies show dose-dependent suppression of MPNST growth. Ongoing work seeks compensatory pathways involving acetate and lipid metabolism that may mediate resistance and reveal therapeutic strategies targeting the intersection of metabolism and epigenetic regulation.

Graduate publications