Molecular Pathology Section
- Three distinct classes of CTCF & BORIS (also known as CTCFL) binding in epigenetic regulation of the genome
- 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 paralogous proteins, CTCF and BORIS (CTCFL), 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. BORIS (CTCFL) is a paralogous gene that carries the same DNA binding domain as CTCF but is normally expressed only during spermatogenesis. In cancer, CTCF appears to function as a tumor suppressor gene whereas BORIS becomes aberrantly expressed in many cancers – thus is classed as a cancer-testis gene and is a possible target for immunotherapy. Approaches utilizing cell-based assays and transgenic/knockout mice and next-generation sequencing (NGS) technologies (e.g., RNA-seq, ATAC-seq, ChIP-seq and Hi-C) are used to probe the molecular functions of these uniquely paired proteins.
Ph.D., 1981, Cancer Research Center, Moscow
M.A., 1977, Institute of Physics, UK
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 (MPS) in the Laboratory of Immunopathology where they first identified CTCF in Drosophila, mice, and humans – and later identified its paralogue BORIS. Dr. Lobanenkov’s team characterized the novel CTCF & BORIS proteins as being universally involved in the epigenetic regulation of mammalian cellular and viral genomes. His section, which moved to the Laboratory of Immunogenetics in 2012, currently works to understand how genome-wide, CTCF/BORIS-binding sequences regulate different functions, including inter- and intra-chromosomal 3D 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.
Rivero-Hinojosa S, Pugacheva EM, Kang S, Méndez-Catalá CF, Kovalchuk AL, Strunnikov AV, Loukinov D, Lee JT, Lobanenkov VV. The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis. Nat Commun. 2021 Jun 22;12(1):3846.
Pugacheva EM, Kubo N, Loukinov D, Tajmul M, Kang S, Kovalchuk AL, Strunnikov AV, Zentner GE, Ren B, Lobanenkov VV. CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention. Proc Natl Acad Sci U S A. 2020 Jan 28;117(4):2020-2031.
Lobanenkov VV, Zentner GE. Discovering a binary CTCF code with a little help from BORIS. Nucleus. 2018 Jan 1;9(1):33-41.
Pugacheva EM, Rivero-Hinojosa S, Espinoza CA, Méndez-Catalá CF, Kang S, Suzuki T, Kosaka-Suzuki N, Robinson S, Nagarajan V, Ye Z, Boukaba A, Rasko JE, Strunnikov AV, Loukinov D, Ren B, Lobanenkov VV. Comparative analyses of CTCF and BORIS occupancies uncover two distinct classes of CTCF binding genomic regions. Genome Biol. 2015 Aug 14;16(1):161.
Klenova EM, Morse HC 3rd, Ohlsson R, Lobanenkov VV. The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. Semin Cancer Biol. 2002 Oct;12(5):399-414.
Ohlsson R, Renkawitz R, Lobanenkov V. CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends Genet. 2001 Sep;17(9):520-7.
The Molecular Pathology Section study paralogous DNA binding proteins CTCF and BORIS (also known as CTCFL) in 3D genome organization and gene regulation in normal and pathological contexts including; spermatogenesis, evolution, development and cancer.