Matias A. Alvarez-Saavedra, Ph.D.

Research

Unraveling the mechanisms that control gene expression via changes in chromatin accessibility is of fundamental importance to understanding normal cellular identity as well as malignancy. Aberrant transcriptional regulation and cell cycle progression resulting in altered chromatin structure and genomic instability underlies many cancers and neural pathologies. My work in the Reinberg lab will address the propagation and formation of chromatin signatures and gene activation under homeostatic conditions, and such information will have important implications for potential mechanisms that are altered in diseased states.

I plan to address the interplay between distinct and dynamic processes that function in the accurate propagation of appropriate chromatin domains during DNA replication and in the output to transcription of a key chromatin signature in embryonic stem cells (ESCs) before and after its restructuring during differentiation. These studies will likely give rise to general models that may explain how the dynamic state of chromatin is preserved through the replicating and transcribing machineries with which it interfaces. My work will probe aspects of the molecular mechanisms of epigenetics by addressing the specific means by which metastable transcriptional states are established in response to developmental and environmental signals, and persist throughout the course of cell division. In addition, the study of chromatin domains may highlight possible therapeutic interventions in the case of diseased states such as cancer.