Genetics, Epigenetics and Metabolism Research Program

University Of Rochester, Rochester NY

Investigators

Abstract

GENETICS, EPIGENETICS AND METABOLISM RESEARCH PROGRAM: PROJECT SUMMARY/ABSTRACT The Genetics, Epigenetics and Metabolism (GEM) research program aims to serve the mission of Wilmot Cancer Institute (Wilmot) through fundamental basic science research that provides new insight into the mechanisms that give rise to genetic and epigenetic variability and their roles in driving cellular plasticity and tumor cell phenotypes; by defining how cellular and organismal aging exposes new vulnerabilities that enhance cancer risk; and by uncovering the ways in which oncogenic insults converge on cancer cell metabolism to reveal new avenues for therapeutic intervention. Led by Paula Vertino, PhD, and Darren Carpizo, MD, PhD, the GEM program consists of 29 members from 13 Departments and two schools across the University of Rochester. The GEM program cultivates scientific synergies between members through monthly program meetings and participation in topic-focused working groups (e.g., Chromatin Collective, RNA Cluster, Metabolism Meeting), as well as weekly cancer seminar series and program retreats. Since 2019, GEM members have published 289 cancer-relevant publications, of which 69 (24%) arose from intra-programmatic collaborations and 63 (22%) from inter-programmatic collaborations and 206 (71%) from inter-institutional collaborations. GEM members currently hold $4.68 million in annual direct peer-reviewed, cancer-relevant funding, with 15% arising from NCI awards. Key achievements include: 1) the successful renewal of a GEM-driven, multi-institutional P01 focused on comparative genomics of longevity and the identification of epigenome erosion and transposon-driven immune response as a potentially reversible mediator of aging; 2) key advances in understanding how mutations in epigenetic regulators and signals from the microenvironment promote pancreatic cancer cell plasticity, which is being leveraged toward a new Phase I, investigator-initiated study; 3) the discovery of new mechanisms of RNA processing, splicing, and turnover with implications for myelodysplastic syndrome and therapeutic intervention. Guided by Wilmot catchment area priorities, the GEM program strives to translate novel findings through Wilmot’s Translational Research Groups. GEM embraces principles of community-engaged research to guide its studies by engaging in bidirectional communication about community priorities in collaboration with the Community Outreach and Engagement (COE) Office. Overall, the GEM program promotes center-wide goals for improvements in cancer outcomes in Central and Western New York. Future plans include enhancing GEM translational impact by leveraging cross-program opportunities with Cancer Microenvironment (CM) around splicing defects in hematologic malignancies, and with Cancer Prevention and Control (CPC) around epigenetic ‘aging’ and quality of life. GEM seeks to further develop its cancer metabolism focus, multi-omics applications, and to expand target discovery and preclinical modeling efforts in alignment with Wilmot’s strategic goal of expanding developmental therapeutics capabilities.