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Vasily M. Studitsky, PhD
Co-Leader, Cancer Epigenetics
- PhD, Biochemistry, Institute of Molecular Biology, 1988
- MS, Biochemistry, Moscow State University, 1984
Honors & Awards
- Annual Wayne State University College Teaching Award 2002
- Annual First Prize for Research, Institute of Molecular Biology, Moscow, Russia 1988
Epigenetic mechanisms of gene expression and regulation
- Mechanisms of histone survival and exchange during Pol II transcription: role of histone chaperones and transcription factors during transcription through chromatin.
- Mechanisms of distant communication during gene regulation.
- Mechanisms of DNA repair in chromatin.
- Development of FACT- and PARP1-targeted anti-cancer drugs.
Development and functioning of higher organisms critically depends on properly regulated gene expression. Regulation of gene expression occurs primarily at the initial step (transcription) and involves DNA sequences, protein factors and dynamic changes in structure of DNA-protein complexes (chromatin). The major research goal in my laboratory is to understand the molecular mechanisms and regulation of the vital process of eukaryotic transcription in chromatin, and the role of the factors involved in cancer development and human aging (e.g. hFACT and hPARP1) in this process. This goal will be achieved using a combination of molecular genetics, genomics, biochemical, single-particle, structural and computational modeling approaches. Currently our efforts are focused in two primary directions: 1. The mechanisms of gene regulation over a distance (by enhancers & insulators), and 2. The mechanisms and regulation of transcript elongation through chromatin by RNA polymerase II.
Distant regulation of gene transcription initiation is mediated by direct interaction between proteins bound at communicating DNA elements and involves looping of intervening DNA/chromatin regions (1). Our research focuses on the following critical questions: What features of DNA/chromatin template allow efficient communication over a distance? What are distinct features of the regulatory elements that are capable of action over a distance? We have adopted relatively simple, highly purified and efficient experimental systems for quantitative analysis of enhancer action over a distance in vitro (2). This simple experimental system allowed us to identify elements of DNA and chromatin structure, as well as protein factors that mediate distant gene regulation (unpublished).
Since 1998 our studies have been focused on analysis of histone survival during transcription by Pol II (funded by NIH RO1). We have established a “minimal” experimental system that maintains single- and multiple-round transcription through various defined mono- and polynucleosomes by yeast and human RNA polymerase II (3). This system faithfully recapitulates numerous features of transcribed chromatin described in vivo and allows their molecular analysis in vitro. Using this system, we have discovered a novel Pol II-specific mechanism involving survival of core histones and their modifications without even transient histone dissociation from DNA (4). These features of the mechanism suggest that it is likely used for maintenance of chromatin structure and the “histone code” that is particularly important during genomic transcription (5,6). It is also important for chromatin-specific DNA repair (7). The most recent focus of our studies is on the mechanism of action of various elongation factors (TFIIS) and histone chaperones (hFACT & hPARP1) facilitating histone survival during Pol II transcription. Importantly, both hFACT & hPARP-1 are involved in carcinogenesis and are important targets for anti-cancer drugs.
Han-Wen Chang MS, PhD
Ekaterina Nizovtseva MS
Elena Kotova MS
Gaykalova, D.A., Kulaeva, O.I., Volokh, O., Shaytan, A.K., Hsieh, F.K., Kirpichnikov, M.P., Sokolova, O.S. and Studitsky, V.M. (2015) Structural Analysis of Nucleosomal Barrier to Transcription. Proc. Natl. Acad. Sci. USA, in press. PubMed
Pestov, N.A., Gerasimova, N.S., Kulaeva, O.I. and Studitsky, V.M. (2015) Structure of Transcribed Chromatin is a Sensor of DNA Damage. Sci. Adv. 1, e1500021.
Clauvelin, N., Lo, P., Kulaeva, O.I., Nizovtseva, E.V., Diaz-Montes, J., Zola, J., Parashar, M., Studitsky, V.M. and Olson, W.K. (2015) Nucleosome positioning and composition modulate in silico chromatin flexibility. J Phys Condens Matter 27, 064112. PubMed
Chang, H.W., Kulaeva, O.I., Shaytan, A.K., Kibanov, M., Kuznedelov, K., Severinov, K.V., Kirpichnikov, M.P., Clark, D.J. and Studitsky, V.M. (2014) Analysis of the mechanism of nucleosome survival during transcription. Nucleic Acids Res. 42, 1619-27. PubMed
Kulaeva, O.I., Hsieh, F.K., Chang, H.W., Luse, D.S. and Studitsky, V.M. (2013) Mechanism of transcription through a nucleosome by RNA polymerase II. Biochim. Biophys. Acta 1829, 76-83. PubMed
Hsieh, F.K., Kulaeva, O.I., Patel, S.S., Dyer, P.N., Luger, K., Reinberg, D. and Studitsky, V.M. (2013) Histone chaperone FACT action during transcription through chromatin by RNA polymerase II. Proc. Natl. Acad. Sci. USA 110, 7654-9. PubMed
Kulaeva, O.I., Nizovtseva, E.V., Polikanov, Y.S., Ulianov, S.V. and Studitsky, V.M. (2012) Distant activation of transcription: mechanisms of enhancer action. Mol Cell Biol 32, 4892-7. PubMed
Gaykalova, D.A., Nagarajavel, V., Bondarenko, V.A., Bartholomew, B., Clark, D.J. and Studitsky, V.M. (2011) A polar barrier to transcription can be circumvented by remodeler-induced nucleosome translocation. Nucleic Acids Res. 39, 3520-8. PubMed
Kulaeva, O.I., Hsieh, F.K. and Studitsky, V.M. (2010) RNA polymerase complexes cooperate to relieve the nucleosomal barrier and evict histones. Proc. Natl. Acad. Sci. USA 107, 11325-30.
Hsieh, F.K., Fisher, M., Ujvari, A., Studitsky, V.M. and Luse, D.S. (2010) Histone Sin mutations promote nucleosome traversal and histone displacement by RNA polymerase II. EMBO Rep. 11, 705-10. PubMed
Kulaeva, O.I., Gaykalova, D.A., Pestov, N.A., Golovastov, V.V., Vassylyev, D.G., Artsimovitch, I. and Studitsky, V.M. (2009) Mechanism of chromatin remodeling and recovery during passage of RNA polymerase II. Nat Struct Mol Biol 16, 1272-8. PubMed