Bromodomains, lysine acetylation, epigenetic readers, transcription, Nut Midline Carcinoma. Epigenetics, Transcription, Modular domains, Histones, Drug discovery, X-ray crystallography
cancer cell lines (NCI60, CRC, melanoma, NMC)
Recombinant biochemistry, biophysical techniques for protein:protein and protein ligand interactions (ITC, AUC, SPR, BLI, DSF, PX, SAXS), gene expression profiline (Affymetrix/Illumina/RNA-seq), deep sequencing (ChIP-seq), analysis of histone marks in a cellular context (IHC, WB, ChiP), in vitro proliferation (MTT), apoptosis, siRNA, genetic transfection, confocal imaging, FRAP, nBRET.
Our laboratory collaborated with groups that offer complimentary skill-sets, including proteomics (AP/MS, SILAC, iTRAQ), access to cell line collections (CRC, melanoma, breast, etc ), mass-spectrometry for protein:protein/protein:ligand interactions (HX/MS), bioinformatic infrastructure and expertise (ChIP-seq, RNA-seq, gene expression profiling) and synthetic chemistry.
Our group is interested in the role of BET (bromo and extra-terminal) proteins in transcription, their mode of interaction with different transcriptional components, their deregulation in disease and their direct inhibition by small molecule inhibitors. To this end we are (a) generating novel chemical tools that can be used to selectively target these proteins in order to delineate their overlapping roles in different cellular contexts, (b) characterizing their network of interacting partners in order to establish their contribution to different transcriptional programmes, (c) examining their controbution to transcriptional programs by directly inhibiting them in different disease contexts and (d) examining their deregulation when they are fused to the NUT protein, in NUT midline carcinomas. Beyond BETs we are interested in the generation of chemical tools that selectively or non selectively target bromodomain containing proteins as well as in defining the biological role of readers of lysine acetylation.
Director of graduate studies, SGC Advisory Committee, University of Tsukuba International PhD program Biochemical Society – Genes theme Panel