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Theme 1: Genetic and Epigenetic Alterations in Cancer

Theme 2: Redox and Metabolic Dysregulation in Cancer

Theme 3: DNA Damage and Repair in Cancer
 

These major research themes collectively address critical aspects of cancer biology, positioning the CC Program at the forefront of discovery to reduce the burden of cancer in Vermont and northern New York.

The CC program members’ expertise has synergy in the area of epigenetics and genetics, with a collective objective to explore multiple facets of epigenetic regulation in normal and cancer cells. Investigators collaborate on multiple cancer research projects that explore molecular mechanisms that safeguard from cancer initiation and progression, study the functions of epigenetic regulators mutated in cancer, define the epigenetic programming imposed through aberrant signal transduction cascades in cancer, and validate epigenetic targets for potential therapeutic intervention and biomarker development. By identifying key drivers of cancer development, the program aims to elucidate fundamental mechanisms of cancer and potential targets for precision therapies.

All tumors exist in an increased oxidative environment. Tumor adaption involves the increased production of oxidants, referred to as oxidative stress, by reconfiguring their metabolism. Through comprehensive studies of sources of oxidants, perturbations of metabolic pathways and high-resolution mapping of oxidant-induced modifications to proteins, this theme seeks to understand how redox dysregulation contributes to cancer phenotypes. An additional goal is to exploit these insights to develop novel redox-based therapeutic approaches, capitalizing on structural insights, and chemical moieties to precisely target effectors or sites of oxidative modifications, some of which have been implemented in in FDA-approved drugs.

The CC program benefits from collective expertise of structural biologists and biochemists that study DNA damage repair mechanisms in cancer. Researchers focus on understanding how defects in DNA repair drive oncogenesis, investigating processes like base excision repair, double strand break repair and translesion synthesis. These investigations provide insight into how cancer cells exploit DNA damage responses, with the ultimate aim of identifying therapeutic strategies that selectively target cancer cells while preserving the integrity of normal tissues.