Histone modifications (such as acetylation and methylation) represent one fundamental mechanism ensuring reliable gene expression through the life of a cell.  The wrong modifications may turn on or off the genes at the wrong time, causing human diseases.  The disease we are currently studying is called synovial sarcoma, one most common soft tissue malignancy in children and young adults, for which there is unfortunately no curative therapy.  We are highly motivated to learn mechanistically how synovial sarcoma forms, and therapeutically how to stop the pathogenesis of this deadly disease.  To this end, my laboratory focuses on histone deacetylases (HDACs), a class of enzymes that remove the acetyl-lysine (Kac) marks on a histone and alter chromatin structure to interfere with transcription.  Particularly, our efforts are directed to i) combine genomics and proteomics to investigate the global impact of individual HDACs and their protein complexes on chromatin remodeling and gene expression, to uncover distinct HDAC requirements for synovial sarcomagenesis, ii) define novel mechanisms of HDAC action by comprehensively searching for non-histone substrates for HDACs and characterizing their functions in transcription-independent oncogenic pathways, and iii) develop new strategies that specifically and effectively target the HDAC biology of synovial sarcoma, and assess their therapeutic value using preclinical models. Given the overlapping of HDAC activities across diverse cell types, completion of these studies will likely provide us with novel “druggable” targets to treat a broad range of human diseases other than synovial sarcoma.