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Srividya Bhaskara

Assistant Professor of Radiation Oncology and 
Adjunct Assistant Professor of Oncological Sciences

Bhaskara

B.S. University of Madras, Chennai, India

M.S. Institute of Basic Medical Sciences, India

Ph.D. University of Tennessee

Research

References

srividya.bhaskara@hci.utah.edu

Vidya Bhaskara's Lab Page

Vidya Bhaskara's Pubmed Literature Search

Molecular Biology Program

Histone deacetylases, Genome Stability, DNA repair, DNA replication, Chromatin, Cancer Therapeutics

Research

The Bhaskara Lab studies Epigenetics, DNA damage response, DNA repair, DNA replication and chromatin structure.

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) target histones and other non-histone proteins with important roles in cell survival and cell cycle progression. Changing the equilibrium between acetylation and deacetylation can adversely affect the normal functioning of cellular processes and cell cycle progression, and result in the development of various cancers. Several HDAC inhibitors are in clinical trials and two of these are FDA approved for the treatment of T-cell lymphoma. One goal of genetic studies of HDACs is to elucidate the function of individual enzymes and to define the actual therapeutic target(s) of HDAC inhibitors, which in turn might pave the way for the design of more specific inhibitors.

The Bhaskara lab research interest is to understand how histone deacetylases (Hdacs) control genome stability. The lab goal is to decipher the basic mode-of-action of specific Hdacs, which are targets of pan-Hdac inhibitors currently used in the clinic for cancer therapy. The lab's overall objective is to determine better and more effective Hdac inhibitors for use in cancer treatment. The lab uses conditional knockout mouse models and cutting-edge molecular biology, cell biology, biochemical techniques to understand the link between Hdacs and genome stability.

Projects in the lab:
Project  1: To investigate the mechanism by which HDACs (specifically HDAC1,2) control DNA damage response and DNA repair.

Project  2: Determine functions for HDACs (specifically HDAC1,2) during DNA replication in mammalian cells.

Project  3: Role for HDACs (specifically HDAC1,2) in modulating chromatin structure to maintain genome stability.

Project  4: Utilize the knowledge gained from Projects 1-3 towards designing better therapy for a subset of cancers.

References

Selected References

  1. The deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B cell development. Stengel K, Barnett K, Wang J, Liu Q, Hodges E, Hiebert S, Bhaskara S (in press, 2017). Proc Natl Acad Sci U S A.
  2. HDAC1,2 inhibition and doxorubicin impair Mre11-dependent DNA repair and DISC to override BCR-ABL1-driven DSB repair in Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia.LID - 10.1038/leu.2017.174 [doi]. Promod ST, Johnson DP, Bennett SE, Dennis EM, Banowsky BG, Jones SS, Shearstone JR, Quayle SN, Min C, Jarpe M, Mosbruger T, Pomicter AD, Miles RR, Chen WY, Bhalla KN, Zweidler-McKay PA, Shrieve DC, Deininger MW, Chandrasekharan MB, Bhaskara S (2017). (Epub ahead of print) Leukemia.
  3. Histone deacetylases 1 and 2 regulate DNA replication and DNA repair: potential targets for genome stability-mechanism-based therapeutics for a subset of cancers. Bhaskara S (2015). “Invited Perspective Review.”Cell Cycle14(12), 1779-85.
  4. Histone deacetylases 1 and 2 maintain S-phase chromatin and DNA replication fork progression. Bhaskara S*, Jacques V, Rusche JR, Olson EN, Cairns BR, Chandrasekharan MB (2013). Epigenetics Chromatin6(1), 27. *Corresponding Author
  5. HDAC1,2 inhibition impairs EZH2- and BBAP-mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma. Johnson DP, Spitz GS, Tharkar S, Quayle SN, Shearstone JR, Jones S, McDowell ME, Wellman H, Tyler JK, Cairns BR, Chandrasekharan MB, Bhaskara S (2015). Oncotarget6(7), 4863-87.
  6. Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique.Bhaskara S (2016). J Vis Exp, (107), e53647.
  7. Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control.Bhaskara S, Chyla BJ, Amann JM, Knutson SK, Cortez D, Sun ZW, Hiebert SW (2008). Mol Cell30(1), 61-72. Highlighted in Nature Cell Biology Research highlights: "Histone deacetylases repair DNA."
  8. Hdac3 is essential for the maintenance of chromatin structure and genome stability.Bhaskara S, Knutson SK, Jiang G, Chandrasekharan MB, Wilson AJ, Zheng S, Yenamandra A, Locke K, Yuan JL, Bonine-Summers AR, Wells CE, Kaiser JF, Washington MK, Zhao Z, Wagner FF, Sun ZW, Xia F, Holson EB, Khabele D, Hiebert SW (2010). Cancer Cell18(5), 436-47.
  9. Role for histone deacetylase 3 in maintenance of genome stability.Bhaskara S, Hiebert SW (2011). Cell Cycle10(5), 727-8.
  10. HDAC3 is essential for DNA replication in hematopoietic progenitor cells. Summers AR, Fischer MA, Stengel KR, Zhao Y, Kaiser JF, Wells CE, Hunt A, Bhaskara S, Luzwick JW, Sampathi S, Chen X, Thompson MA, Cortez D, Hiebert SW (2013). J Clin Invest123(7), 3112-23.
  11. Inhibition of histone deacetylase 3 causes replication stress in cutaneous T cell lymphoma. Wells CE, Bhaskara S, Stengel KR, Zhao Y, Sirbu B, Chagot B, Cortez D, Khabele D, Chazin WJ, Cooper A, Jacques V, Rusche J, Eischen CM, McGirt LY, Hiebert SW (2013). PLoS One8(7), e68915.
  12. The coactivator role of histone deacetylase 3 in IL-1-signaling involves deacetylation of p65 NF-kappaB. Ziesche E, Kettner-Buhrow D, Weber A, Wittwer T, Jurida L, Soelch J, Muller H, Newel D, Kronich P, Schneider H, Dittrich-Breiholz O, Bhaskara S, Hiebert SW, Hottiger MO, Li H, Burstein E, Schmitz ML, Kracht M (2013). Nucleic Acids Res41(1), 90-109.
  13. A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters. Hatzi K, Jiang Y, Huang C, Garrett-Bakelman F, Gearhart MD, Giannopoulou EG, Zumbo P, Kirouac K, Bhaskara S, Polo JM, Kormaksson M, MacKerell AD Jr, Xue F, Mason CE, Hiebert SW, Prive GG, Cerchietti L, Bardwell VJ, Elemento O, Melnick A (2013). Cell Rep4(3), 578-88.
  14. Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks. Knutson SK, Chyla BJ, Amann JM, Bhaskara S, Huppert SS, Hiebert SW (2008). EMBO J27(7), 1017-28.
  15. Histone deacetylase inhibitor treatment induces 'BRCAness' and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells. Ha K, Fiskus W, Choi DS, Bhaskara S, Cerchietti L, Devaraj SG, Shah B, Sharma S, Chang JC, Melnick AM, Hiebert S, Bhalla KN (2014). Oncotarget5(14), 5637-50.
  16. Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer. Chan E, Arlinghaus LR, Cardin DB, Goff L, Berlin JD, Parikh A, Abramson RG, Yankeelov TE, Hiebert S, Merchant N, Bhaskara S, Chakravarthy AB (2016). Radiother Oncol119(2), 312-8.
  17. The DNA damage mark pH2AX differentiates the cytotoxic effects of small molecule HDAC inhibitors in ovarian cancer cells. Wilson AJ, Holson E, Wagner F, Zhang YL, Fass DM, Haggarty SJ, Bhaskara S, Hiebert SW, Schreiber SL, Khabele D (2011). Cancer Biol Ther12(6), 484-93.

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Last Updated: 7/31/17