Biography

The crux of my research goal over the years has been to understand exactly how RNA polymerase II (RNAPII) acquires selectivity for subsets of genes in a regulated manner. My strategy was to gain a sound grasp of RNAPII-mediated transcription as the template complexity was progressively increased. Efforts by my group through the years initiated with defining the basic prerequisites for RNAPII transcription from a minimal, naked DNA template, and then proceeded to the functional analysis of even more complex arrays of activities that together reconstitute chromatinized templates that exhibit different extents of compaction and others that refurbish the templates into a state amenable to transcription. This latest endeavor entails studies of the post-translational modifications of histones and their potential epigenetic character. As the field continues to advance our understanding of the dynamic generation and propagation of chromatin domains that facilitate or impede transcription, it is also an opportune time to enlarge the scope of these investigations and tackle the workings of such chromatin domains within the context of higher-order genomic structures.

We have embarked on an intensive and highly enriching collaborative effort with Esteban Mazzoni, an accomplished and respected researcher in neuronal development here at NYU. We investigated the contribution of CCCTC-binding factor (CTCF) in the generation of topologically associated domains (TADs), a fundamental structural unit of the genome, within the context of segmental Hox gene expression in the mammalian system. Our efforts thus far established that CTCF functions as an insulator protein essential for establishing tight chromatin borders between active and repressive chromatin within the HoxA cluster. We were surprised to find that CTCF functions not by preventing the spread of repressive chromatin, but rather by preventing the invasion of active transcription. These findings laid the platform for the studies proposed herein. My interactions with Esteban and his group have been remarkably productive, stimulating and fun, and highlight this stage of my research career as being the most invigorating.