Bio
Our goal is to discover and understand the mechanistic basis of epigenetic regulation of aging, genomic integrity and gene expression. The most fundamental level of epigenetic regulation is provided by the packaging of our DNA together with histone proteins to make chromatin, and the opposite process of removal of histones from the DNA. These chromatin assembly and disassembly processes physically block or permit, respectively, access of the cellular machinery to the genetic information carried by our DNA, thereby playing a critical role in controlling all genomic processes. We focus on understanding how chromatin is disassembled and reassembled by histone chaperone proteins, ATP-dependent chromatin remodeling machines and post-translational modifications of the globular domains of the core histones, in order to discover new mechanisms whereby chromatin regulates aging, gene expression and genomic integrity. Our studies use a combination of molecular genetics in budding yeast, tissue culture studies, biochemistry and biophysical approaches. The proteins and processes that we study are so highly conserved through eukaryotic evolution, that what we learn in the highly genetically malleable yeast system is directly relevant to the situation in humans. In addition to learning how chromatin regulates fundamental processes in the cell, our studies are helping us to understand how defects in the chromatin structure lead to gene dysfunction and genomic instability, in turn causing human aging and disease states including cancer and leukemia.