Le Su, PhD
Molecular mechanisms of sarcomagenesis
Location: 601 Genome Way, Huntsville, AL 35806
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.
About Le Su, PhD
Le Su, PhD, has been actively involved in sarcoma research for nearly ten years. As a Junior Fellow at HudsonAlpha, his major focus is on chromosomal translocation-associated sarcomagenesis in children and young adults. Before joining HudsonAlpha in 2016, Su led a molecular proteomics laboratory as a postdoctoral fellow at the University of British Columbia in Canada where he also earned his PhD in Cell Biology (2014). His research efforts directly led to fundamental breakthroughs that define a crucial role for synovial sarcoma-specific SS18-SSX chimeric oncoprotein in epigenetic dysregulation of tumor suppressor pathways. Through close collaboration with clinical scientists, these mechanistic studies have successfully been brought into clinical trials that opened in several medical institutes across Canada. Su’s research interests stem from his previous findings that histone deacetylase (HDAC) inhibitors block SS18-SSX transcriptional activity and induce synovial sarcoma cell death. Recently, this epigenomic research has been extended unexpectedly to the ubiquitin system by which HDAC inhibitor treatment causes SS18-SSX depletion. The underlying mechanism may not only support the first targeted strategy to treat currently incurable synovial sarcoma, but also revolutionize our understanding of the anti-cancer action of HDAC inhibitors.
2014 PhD in Cell Biology, University of British Columbia, Canada
2007 MSc in Molecular Proteomics, Brock University, Canada
2005 BSc in Biochemistry, Yantai University, China
2015-present Junior Fellow, HudsonAlpha Institute for Biotechnology
2014-2015 Postdoctoral Fellow, Molecular Oncology, University of British Columbia, Canada
2016 Childhood Cancer Research Grant, St. Baldrick’s Foundation
2016 JOA Annual Congress Travel Award, Japanese Orthopaedic Association, Yokohama
2013 Research Award of the Year, University of British Columbia, Canada
2012 Top 10 Research Achievements of the Year, Canadian Cancer Society
2010 Young Investigator Award, Connective Tissue Oncology Society