Shilatifard Laboratory
Recent Videos from the Shilatifard Lab
Enhancing HIV-1 latency reversal through regulating the elongating RNA Pol II pause-release by a small-molecule disruptor of PAF1C
A recent publication in Science Advances from the Simpson Querrey Institute for Epigenetics describes the regulation of paused RNA Polymerase II in HIV latency reversal and the discovery of a possible small molecule disruptor in this process.
SPT6 Functions in Transcriptional Pause/Release via PAF1C Recruitment
A recent publication in Molecular Cell from the Simpson Querrey Institute for Epigenetics describes new understandings of the RNA polymerase II elongation complex. SPT6 recruits the PAF1 complex and removes NELF in order for RNA polymerase II to be released.
Transcription Elongation Checkpoint Discovered
A recent publication in Molecular Cell from the Simpson Querrey Institute for Epigenetics describes how the loss of SPT5 from RNA polymerase II, results in the degradation of the largest subunit RPB1. These findings provide insight into productive elongation and how the misregulation of SPT5 is associated with human diseases.
Epigenetic Targeted Therapy of Gene Expression in Leukemic Cells
A recent publication in Nature Cancer from the Simpson Querrey Institute for Epigenetics that describes the effects of ASXL1 mutations in BAP1 and the role it plays in leukemic pathogenesis. As well as the discovery of an inhibitor that could help.
Uncoupling Histone H3K4 trimethylation from transcription
A recent publication in Nature Genetics from the Simpson Querrey Institute for Epigenetics describes the balance between COMPASS, PRC2, and DNA methylation. This discovery disentangles Histone H3 K4 trimethylation from transcription and reveals how these players work in concert to dictate transcriptional decisions.
Balancing Regulation of Gene Expression in Cancer
Mutations in the COMPASS and Polycomb families of chromatin modifiers have been identified that disrupt the balanced regulation of gene expression (Wang et al., Nature Medicine 2018) (Piunti & Shilatifard, Science 2016). Researchers have discovered mechanisms to restore expression of tumor suppressor genes in several cancers, including bladder cancer, which are being evaluated in ongoing clinical trials.
Epigenetics and Cancer with Ali Shilatifard
Northwestern University Feinberg School of Medicine's Breakthroughs Podcast features Ali Shilatifard.
Ali Shilatifard’s Lab
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What We Do
The regulation of gene expression by RNA polymerase II is essential for development and differentiation, and its misregulation contributes to the pathogenesis of many forms of cancers. The goal of our laboratory is to define the molecular mechanisms underlying cancer pathogenesis and to identify potential targets for therapy. These studies have been done through detailed understanding of proteins and protein complexes that regulate chromatin modifications, transcriptional initiation, and transcriptional elongation. Several of such findings from our lab our now under clinical studies for the treatment of bladder cancer and pediatric brain tumors.
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