Alexandros Tzatsos, MD, PhD
Instructor, Department of Medicine, Harvard Medical School
Assistant Geneticist, Cancer Center, Massachusetts General Hospital
DF/HCC Program AffiliationGastrointestinal MalignanciesCancer Genetics
My research objectives aim to define how changes in the epigenetic landscape influence the initiation and maintenance of human cancers and to identify the biochemical mediators involved in these processes. By employing a systems biology approach, I have identified members of the Jumonji-domain containing histone demethylase family as important regulators of gastrointestinal malignancies. Functionally, gain and loss-of-function experiments coupled to genome-wide gene expression and chromatin immunoprecipitation studies led to the discovery of a key epigenetic program, through which histone demethylases subvert cellular differentiation and sustain metabolic homeostasis, leading to tumor progression. To this end, I have generated new genetically engineered mouse models to ablate and overexpress the identified histone demethylases in vivo. Given the reversibility of epigenetic changes, histone demethylases represent excellent candidates for the development of new therapeutics.
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