Dr. Atanassov obtained his Ph.D. in Molecular Biology from the Bulgarian Academy of Sciences. During his doctoral studies, he focused on elucidating the DNA repair mechanisms that cancer cells employ to counter the effects of the genotoxic agents used in chemotherapy. He spent half of his doctoral studies as a participant in the Graduate Partnership Program at NIH, where he was working with Barbara Davis and J. Carl Barrett to study the role of the breast cancer-associated BRCA2 in homologous recombination and DNA repair. In 2007, Dr. Atanassov joined the laboratory of Dr. Sharon Dent at MD Anderson Cancer Center, as a postdoctoral fellow. Dr. Atanassov’s postdoctoral studies were focused on understanding the roles that a multi-subunit chromatin modifying complex called SAGA (SPT-GCN5-ADA) has in development and disease. Dr. Atanassov was later promoted to an Instructor in the Department of Epigenetics and Molecular Carcinogenesis at MD Anderson Cancer Center, and in 2016 to an Assistant Professor in the same department. In 2017, Dr. Atanassov joined the faculty of the Pharmacology and Therapeutics department at Roswell Park Comprehensive Cancer Center where he will continue to work with world-class scientists and clinicians to connect the molecular findings in his laboratory to cancer treatments in the clinic.
Research in my laboratory is focused on elucidating the molecular mechanisms by which chromatin modifying enzymes and the complexes they form potentiate tumor formation, growth and metastasis. Although genetic changes in cancer are well recognized, epigenetic changes that alter gene expression patterns have also been found to play a major role during development of this disease in recent years. These changes, affecting post-translational modifications of histones and DNA methylation, are mediated by various chromatin modifying enzymes. Our work has revealed that these enzymes often have functions independent of their canonical roles in transcriptional regulation that are critically important for normal cell growth, survival and response to the environment. We are particularly interested in Ubiquitin Specific Proteases (USPs) that are capable of removing ubiquitin moieties from histones, thus altering the expression patterns of target genes. In recent years many USPs have been directly linked to different stages of cancer progression. For example, USP22 is a member of an 11 gene “death-from-cancer” signature that serves as a predictor for treatment resistance, tumor aggressiveness and metastatic probability in cancer patients. Additionally, ablation of USP44 leads to spontaneous lung cancer in mice whereas its function is required for invasion of breast cancer cells in vitro. Further, in our recent studies we identified two uncharacterized USPs, USP27X and USP51, which are remarkably similar to the cancer-associated USP22, to which their ablation severely impacts tumor growth. Thus, using a variety of biochemical and genetic approaches (e.g. tissue culture and mouse models) our lab aims to 1) define the molecular mechanisms by which USP27X, USP51, and other USPs impact tumor growth, and 2) define the in vivo functions of these USPs during normal development and carcinogenesis.
Misregulation of ubiquitin-proteasome pathways is implicated in the pathogenesis of many human diseases, particularly cancer, and proteasome inhibitors are studied as possible treatments for these diseases. Hence, inhibitors of USPs are particularly attractive for therapeutic intervention; specific inhibition of their function would operate upstream of the proteasome and possibly generate specific and less toxic antitumor therapies. Therefore, it is our long-term goal to connect the mechanistic and molecular findings in our laboratory to cancer.
- Atanassov BS*, Mohan RD, Lan XJ, Kuang J, Lu Y, Lin K, McIvor, Li W, Zhang Y, Florens L, Byrum SD, Mackintosh SG, Davis T, Koutelou E, Wang L, Tang D, Tackett AJ, Washburn MP, Workman JL, Dent SY*. ATXN7L3 and ENY2 coordinate activity of multiple H2B deubiquitinases important for cellular proliferation and tumor growth. Mol Cell. 2016 May 19;62(4):558-71. PMID: 27132940. * co-corresponding authors. (The paper was highlighted in the In the “Research Watch” section of Cancer Discovery Journal, PMID: 27179043)
- Atanassov BS, Evrard YA, Multani AS, Zhang Z, Tora L, Devys D, Chang S, Dent SY. Gcn5 and SAGA regulate shelterin protein turnover and telomere maintenance. Mol. Cell. 2009 Aug 14;35(3):352-64. doi: 10.1016/j.molcel.2009.06.015. PubMed PMID: 19683498.
- Atanassov BS, Dent SY. USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1. EMBO Rep. 2011 Sep 1;12(9):924-30. doi: 10.1038/embor.2011.140. PMID: 21779003.
- Xianjiang Lan, Atanassov BS, Li W, Zhang Y, Florens L , Mohan RD, Galardy P, Washburn MP, Workman JL, and Dent S.Y.R, USP44 is an Integral component of N-COR That Contributes to Gene Repression by Deubiquitinating Histone H2B, Cell Reports, 2016, Nov 22; 17(9) 2382-2393. PMID: 27880911
- Atanassov BS, Koutelou E, Dent SY. The role of deubiquitinating enzymes in chromatin regulation. FEBS Lett. 2011 Jul 7;585(13):2016-23. doi: 10.1016/j.febslet.2010.10.042. Epub 2010 Oct 26. Review. PMID: 20974139. My NCBI