Major Areas of Research
- Three classes of CTCF/BORIS binding in epigenetic regulation
- Regulation of BORIS and its targets in cellular and viral genomes
- Translational research of BORIS repressors and of anti-BORIS immune response directed to cancer diagnostics, therapy, and anti-tumor vaccination
Studies in the Molecular Pathology Section center on the activities of two proteins, CTCF and BORIS, and their roles in normal biology and cancer. CTCF is a ubiquitous, 11-zinc-finger DNA-binding protein involved in transcriptional regulation, reading of imprinted sites, X-chromosome inactivation, and enhancer blocking/insulator function.
In cancer, CTCF appears to function as a tumor suppressor gene. BORIS is aberrantly expressed in many cancers and is thus a cancer/testis gene and a possible target for immunotherapy. Approaches from cell and molecular biology as well as transgenic and knockout mice are used to probe the functions of these uniquely paired proteins.
Dr. Lobanenkov received an M.A. in nuclear physics from the Institute of Physics in 1977 and a Ph.D. in experimental oncology from the Cancer Research Center, Moscow, in 1981. He was molecular carcinogenesis team leader in the All-Union Cancer Center of the former U.S.S.R. and a visiting scholar at the Royal Cancer Hospital, London, until 1990, where he discovered avian CTCF. He was invited to the Fred Hutchinson Cancer Research Center in Seattle as a foreign faculty-in-residence funded by NIH grants.
In 1999, he became chief of the Molecular Pathology Section in the Laboratory of Immunopathology; identified CTCF in Drosophila, mice, and man; and characterized the novel BORIS+CTCF gene family universally involved in epigenetic regulation of mammalian cellular and viral genomes. His section, which moved to the Laboratory of Immunogenetics in 2012, works to understand how genome-wide, CTCF/BORIS-binding sequences regulate different functions, including inter- and intra-chromosomal 3-D DNA-looping interactions, mono-allelic expression of imprinted and non-imprinted genes, X-chromosome inactivation, and regulation of stem/germ cell-specific promoters associated with targeted DNA demethylation.
Kosaka-Suzuki N, Suzuki T, Pugacheva EM, Vostrov AA, Morse HC 3rd, Loukinov D, Lobanenkov V. Transcription factor BORIS (Brother of the Regulator of Imprinted Sites) directly induces expression of a cancer-testis antigen, TSP50, through regulated binding of BORIS to the promoter. J Biol Chem. 2011 Aug 5;286(31):27378-88.
Pugacheva EM, Suzuki T, Pack SD, Kosaka-Suzuki N, Yoon J, Vostrov AA, Barsov E, Strunnikov AV, Morse HC 3rd, Loukinov D, Lobanenkov V. The structural complexity of the human BORIS gene in gametogenesis and cancer. PLoS One. 2010 Nov 8;5(11):e13872.
Suzuki T, Kosaka-Suzuki N, Pack S, Shin DM, Yoon J, Abdullaev Z, Pugacheva E, Morse HC 3rd, Loukinov D, Lobanenkov V.Expression of a testis-specific form of Gal3st1 (CST), a gene essential for spermatogenesis, is regulated by the CTCF paralogous gene BORIS. Mol Cell Biol. 2010 May;30(10):2473-84.
Ohlsson R, Lobanenkov V, Klenova E. Does CTCF mediate between nuclear organization and gene expression? Bioessays. 2010 Jan;32(1):37-50.
Bougel S, Renaud S, Braunschweig R, Loukinov D, Morse HC 3rd, Bosman FT, Lobanenkov V, Benhattar J. PAX5 activates the transcription of the human telomerase reverse transcriptase gene in B cells. J Pathol. 2010 Jan;220(1):87-96.
Smith IM, Glazer CA, Mithani SK, Ochs MF, Sun W, Bhan S, Vostrov A, Abdullaev Z, Lobanenkov V, Gray A, Liu C, Chang SS, Ostrow KL, Westra WH, Begum S, Dhara M, Califano J. Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer. PLoS One. 2009;4(3):e4961.