Research

Regulation of Eukaryotic Gene Expression

Our laboratory investigates the molecular mechanisms that regulate transcriptional and epigenetic processes to control eukaryotic gene expression. Misregulation of these processes not only disrupts the precise spatial and temporal control of gene expression required for embryonic development but also underlies the pathogenesis of cancers, neurodegenerative disorders and other human diseases. Fundamentally motivated by the need for targeted disease therapies, the basic research in our laboratory yields the detailed, mechanistic understanding of molecular pathways that makes these therapies possible. Our efforts to dissect oncogenic mechanisms have recently identified several potential target pathways and small molecule therapies, some of which are now under clinical trial.

Chromosomal Translocation and Mixed Lineage Leukemia

The Shilatifard laboratory studies the biochemical and molecular mechanisms underlying leukemogenesis, identifying potential targets for cancer therapeutics. Watch this original animation to learn more.

                                                     

Transcription in Myc-Related Cancers

Our lab identified the Super Elongation complex (SEC), which regulates gene transcription by RNA Polymerase II. Watch this original animation to learn more about how misregulation of SEC contributes to disease. 

                                                     

Chromatin Biology

We work within the Simpson Querrey Center for Epigenetics, which seeks to explain how environmental conditions interact with DNA to affect human health. Watch this original animation to learn more about how we study epigenetic mechanisms and chromatin biology to develop treatments for cancer and other diseases.

                                                     

Our laboratory has a long history of identifying and characterizing the factors that control transcriptional elongation, the diverse complexes they form to regulate gene expression, and their functional roles in development and disease pathogenesis. Today, our focus encompasses two major groups of regulators: elongation factors, the proteins that directly interact with the post-initiation RNA Pol II complex, and epigenetic modifiers, the enzymes that alter the chromatin through which RNA Pol II must transcribe. While the causative nature of the relationship between transcriptional regulation and chromatin modifications remains unclear, our recent results have led us to a contextual re-evaluation of histone modification’s transcriptional role, taking into consideration both the catalytic and non-catalytic functions of chromatin modifying enzymes.

Active Areas of Investigation