Vasily Studitsky, PhD

Vasily M. Studitsky, PhD
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This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
Learn more about Research Volunteering.

Co-Leader, Cancer Epigenetics

Professor

  • Histone Tails Mediate Distance-Independent EPC

  • Mechanisms and Regulation of Transcription in Chromatin

  • Mechanism of Histone Survival During Pol II Transcription

  • Role of histone chaperones and other proteins during transcription through chromatin

  • Mechanisms of chromatin-specific DNA repair

  • The role of chromatin structure, protein factors and histone modifications

  • Transcriptional Enhancers: Gene Activation over a Distance

  • Distant Enhancer Action: Communication Problem

  • Enhancer-Promoter Communication (EPC) in the Chromatin Fiber

  • Histone Tails Mediate Distance-Independent EPC

     

    Educational Background

    • 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   

    People

    • Elena Bondarenko
      Research Associate
      W209
    • Elena Kotova, MS
      Technical Specialist
      W209
    • Michael DiBello
      Volunteer
      W209
    • Cecilia Verillo
      Volunteer
      W209

    Research Interests

    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.

    Lab Overview

    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.

    Lab Description

    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 the following primary directions: 1. Mechanisms of histone chaperones FACT and PARP1 action during transcription and its regulation. 2. Mechanisms of interaction of sequence-specific regulator proteins (e.g. p53) with DNA organized into chromatin. 3. The mechanisms and regulation of transcript elongation through chromatin by RNA polymerase II, and 4. The mechanisms of gene regulation over a distance (by enhancers & insulators).

    FACT and PARP1 are histone chaperones that can increase chromatin accessibility to various proteins during initiation and elongation of transcription. Importantly, both hFACT & hPARP1 are involved in carcinogenesis and are important targets for anti-cancer drugs. Recently we have studied the mechanisms of FACT- and PARP1-dependent chromatin reorganization. Our research focuses on the following questions: What changes in chromatin structure are involved in the reorganization? How do various anti-cancer drugs affect this process? What are the mechanisms of trapping of the histone chaperones in chromatin?

    Tumor suppressor p53 is a sequence-specific DNA-binding protein, possibly a pioneering factor involved in gene regulation. It has an apparent high affinity to the response elements regulating cell cycle arrest genes (CCA-sites) and a lower affinity to the sites associated with apoptosis (Apo-sites) in vivo. We are trying to understand the mechanisms of interaction of p53 with its binding sites in chromatin. The questions are: Can the differences in affinity be explained by the chromatin context of the binding sites? What changes in chromatin structure are involved in p53-DNA interaction?

    In early 2000 we have established a “minimal” experimental system that maintains transcription through various defined mono- and polynucleosomes by RNA polymerase II. 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 mechanism involving survival of core histones and their modifications without even transient histone dissociation from DNA. These features of the mechanism suggest that it is likely used for maintenance of chromatin structure and the “histone code”. The most recent focus of our studies is on the mechanism of action of histone chaperones FACT & PARP1 during Pol II transcription.

    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. 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. This simple experimental system allowed us to identify elements of chromatin structure and protein factors involved in distant gene regulation.

    Selected Publications

    Sivkina A.L., Karlova M.G., Valieva M.E., McCullough L.L., Formosa T., Shaytan A.K., Feofanov A.V., Kirpichnikov M.P., Sokolova O.S., Studitsky V.M., Electron microscopy analysis of atp-independent nucleosome unfolding by fact. Commun Biol. 5(1): 2, 2022. PMC8748794. https://www.ncbi.nlm.nih.gov/pubmed/35013515.

    Maluchenko N.V., Nilov D.K., Pushkarev S.V., Kotova E.Y., Gerasimova N.S., Kirpichnikov M.P., Langelier M.F., Pascal J.M., Akhtar M.S., Feofanov A.V., Studitsky V.M., Mechanisms of nucleosome reorganization by parp1. Int J Mol Sci. 22(22)2021. PMC8620739. https://www.ncbi.nlm.nih.gov/pubmed/34830005.​

    Nilov D, Maluchenko N, Kurgina T, Pushkarev S, Lys A, Kutuzov M, Gerasimova N, Feofanov A, Svedas V, Lavrik O, Studitsky VM. Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine. International journal of molecular sciences. 2020;21(6):pii: 2159. Epub 2020/04/05. doi: 10.3390/ijms21062159. PubMed PMID: 32245127.

    Kantidze OL, Gurova KV, Studitsky VM, Razin SV. The 3D Genome as a Target for Anticancer Therapy. Trends Mol Med. 2020;26(2):141-9. Epub 2019/11/05. doi: 10.1016/j.molmed.2019.09.011. PubMed PMID: 31679987.

    Kantidze OL, Luzhin AV, Nizovtseva EV, Safina A, Valieva ME, Golov AK, Velichko AK, Lyubitelev AV, Feofanov AV, Gurova KV, Studitsky VM, Razin SV. The anti-cancer drugs curaxins target spatial genome organization. Nat Commun. 2019;10(1):1441. Epub 2019/03/31. doi: 10.1038/s41467-019-09500-7. PubMed PMID: 30926878; PMCID: PMC6441033.

    Chang HW, Nizovtseva EV, Razin SV, Formosa T, Gurova KV, Studitsky VM. Histone Chaperone FACT and Curaxins: Effects on Genome Structure and Function. J Cancer Metastasis Treat. 2019;5:pii: 78. Epub 2019/12/20. doi: 10.20517/2394-4722.2019.31. PubMed PMID: 31853507; PMCID: PMC6919649.

    Shaytan AK, Xiao H, Armeev GA, Gaykalova DA, Komarova GA, Wu C, Studitsky VM, Landsman D, Panchenko AR. Structural interpretation of DNA-protein hydroxyl-radical footprinting experiments with high resolution using HYDROID. Nat Protoc. 2018;13(11):2535-56. Epub 2018/10/21. doi: 10.1038/s41596-018-0048-z. PubMed PMID: 30341436.

    McCullough LL, Connell Z, Xin H, Studitsky VM, Feofanov AV, Valieva ME, Formosa T. Functional roles of the DNA-binding HMGB domain in the histone chaperone FACT in nucleosome reorganization. J Biol Chem. 2018;293(16):6121-33. Epub 2018/03/09. doi: 10.1074/jbc.RA117.000199. PubMed PMID: 29514976; PMCID: PMC5912460.

    Gurova K, Chang HW, Valieva ME, Sandlesh P, Studitsky VM. Structure and function of the histone chaperone FACT - Resolving FACTual issues. Biochim Biophys Acta. 2018;1861:892-904. Epub 2018/07/29. doi: 10.1016/j.bbagrm.2018.07.008. PubMed PMID: 30055319.

    Chang HW, Valieva ME, Safina A, Chereji RV, Wang J, Kulaeva OI, Morozov AV, Kirpichnikov MP, Feofanov AV, Gurova KV, Studitsky VM. Mechanism of FACT removal from transcribed genes by anticancer drugs curaxins. Science advances. 2018;4(11):eaav2131. Epub 2018/11/13. doi: 10.1126/sciadv.aav2131. PubMed PMID: 30417101; PMCID: PMC6221510... Expand

    Additional Publications

    This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
    Learn more about Research Volunteering.