JAMIE ANASTAS, PHD
Baylor College of Medicine
CureSearch Young Investigator Award: 2022-2025
Focus: Pediatric High-Grade Glioma
Project title: Combinatorial targeting of HDACs and LSD1 to treat pediatric brain tumors
Cancer is the leading, disease-related cause of pediatric mortality in the United States, and brain tumors are among the deadliest of all childhood tumors. Outcomes for pediatric high-grade gliomas (pHGGs) range from less than 25% to essentially 0%, in the case of diffuse midline gliomas (DMGs), and these dismal survival rates have not improved in 30 years.
Jamie Anastas, PhD, is a CureSearch Young Investigator conducting research at the Baylor College of Medicine to develop a therapy for pediatric high-grade glioma that takes advantage of a brain tumor vulnerability. Disrupted chromatin regulation is a driver of pediatric brain tumor progression, as seen in reports of promising anti-tumor activity of chromatin-targeting drugs. The studies proposed by Dr. Anastas focus on two classes of chromatin-modifying enzymes—lysine-specific demethylase 1 (LSD1) and histone deacetylases (HDACs) to develop a combination targeted therapy optimized based on molecular markers of on-target activity and a lack of toxicity. Dr. Anastas hypothesizes that combined treatment with two repurposed therapies, an LSD1 inhibitor and an HDAC inhibitor, will block pediatric brain tumor growth by altering tumor cell growth and survival and by enhancing tumor immune targeting.
Project Update: In 2022, Dr. Anastas's team evaluated the activity of three different LSD1 inhibitors and eight different HDAC inhibitors. Dr. Anastas has established protocols for generating mouse models of pediatric brain tumors and is evaluating the on-target activity of LSD1 and HDAC inhibitors in vivo. In 2023, the team will focus on determining whether additional pediatric brain tumor cell types like ependymoma cells are sensitive to the drug combination and perform additional staining on 3XCRISPR model mouse brain tumors.