Mahesh B. Chandrasekharan, PhD

Research Interests

  • Histone Modifications
  • Transcription
  • Genome Stability

Labs

Lab Website

Languages

  • English

Academic Information

  • Departments: Radiation Oncology - Assistant Professor
  • Cancer Center Programs: Nuclear Control of Cell Growth & Differentiation

Academic Office Information

  • 801-581-8793
  • Huntsman Cancer Hospital
    1950 Circle of Hope, Room: 1570
    Salt Lake City, UT 84112

Academic Bio

Dr. Chandrasekharan received his PhD in 2001 from Texas A&M College Station, Texas in Biology. He stayed on as a Post Doctoral Research Associate in Dr. Timothy C. Hall's lab for another two years. He was a post doctoral fellow at Vanderbilt University in Nashville, TN in Dr. Zu-Wen Sun's lab until 2011. He is currently Research Assistant Professor in the Department of Radiation Oncology, Research Scholar at Huntsman Cancer Institute, and a member of the Nuclear Control of Cell Growth and Differentiation program.Dr. Chandrasekharan was awarded MS (Biotechnology) Merit Scholarship by the Department of Biotechnology by the Government of India in 1991 and Biology Doctoral Merit Award by the Department of Biology, Texas A&M University, College Station, TexasDr. Chandrasekharan’s research focus is to understand the regulation of function of histone modifications, which act as epigenetic mechanisms to regulate several aspects of organismal and cellular development, and which are frequently aberrant in cancer. He uses yeast as the primary model system of choice for his studies and intends to extend his findings to mammalian model systems. As a graduate student, he investigated how chromatin remodeling plays an important role in the spatial and temporal regulation of gene expression during plant development. His post-doctoral research was to understand the regulation and function of the evolutionarily-conserved crosstalk between histone H2B ubiquitination and histone H3 lysine 4 and lysine 79 (K4 and K79) methylation. During the course of his post-doctoral studies, he made a novel and rather unexpected discovery that histone H2B ubiquitination stabilizes the nucleosome. He also found that the H2B C-terminal helix modulates H3K4 methylation independent of H2B ubiquitination by providing a ‘docking site’ for Set1-COMPASS (the methyltransferase-containing complex). As an independent investigator, the primary research objective of his laboratory is to continue his post-doctoral work and further understand the intricacies of the trans-histone crosstalk between H2B ubiquitination and H3 methylation.Histone-modifying enzymes involved in the trans-histone crosstalk have garnered much interest in recent times, as they have been implicated in various human diseases, including cancers. Dr. Chandrasekharan’s current research goal is two-fold; first, he intends to understand the basic mechanisms of regulation and functions of these histone-modifying enzymes. Second, he intends to utilize the knowledge gained from his studies of the fundamental mechanisms to obtain insight into disease formation and progression, and develop efficient therapeutics for cancer treatment.

Education History

Type School Degree
Postdoctoral Fellowship Vanderbilt University School of Medicine
Biochemistry, Molecular Biology
Postdoctoral Fellow
Fellowship Institute of Developmental and Molecular Biology, Texas A&M University
Biology
Postdoctoral Research Associate
Doctoral Training Texas A&M University
Biology
Ph.D.
Graduate Training Madurai Kamaraj University
Biotechnology
M.S.
Undergraduate St. Aloysius College, University of Mangalore
Chemistry, Botany and Zoology
B.S.

Global Impact

Education History

Type School Degree Country
Graduate Training Madurai Kamaraj University
Biotechnology
M.S. India
Undergraduate St. Aloysius College, University of Mangalore
Chemistry, Botany and Zoology
B.S. India

Career

Institution Description Country
Dr. Vallakunja Nagaraja’s Laboratory, Centre for Genetic Engineering, Indian Institute of Science Research Technician India

Selected Publications

Journal Article

  1. Bhaskara S, Jacques V, Rusche JR, Olson EN, Cairns BR, Chandrasekharan MB (2013). Histone deacetylases 1 and 2 maintain S-phase chromatin and DNA replication fork progression. Epigenetics Chromatin, 6(1), 27.
  2. Joo HY, Jones A, Yang C, Zhai L, Smith AD 4th, Zhang Z, Chandrasekharan MB, Sun ZW, Renfrow MB, Wang Y, Chang C, Wang H (2011). Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46. J Biol Chem, 286(9), 7190-201.
  3. Chandrasekharan MB, Huang F, Sun ZW (2011). Decoding the trans-histone crosstalk: methods to analyze H2B ubiquitination, H3 methylation and their regulatory factors. Methods, 54(3), 304-14.
  4. Chandrasekharan MB, Huang F, Chen YC, Sun ZW (2010). Histone H2B C-terminal helix mediates trans-histone H3K4 methylation independent of H2B ubiquitination. Mol Cell Biol, 30(13), 3216-32.
  5. Huang F, Chandrasekharan MB, Chen YC, Bhaskara S, Hiebert SW, Sun ZW (2010). The JmjN domain of Jhd2 is important for its protein stability, and the plant homeodomain (PHD) finger mediates its chromatin association independent of H3K4 methylation. J Biol Chem, 285(32), 24548-61.
  6. 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). Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell, 18(5), 436-47.
  7. Nakanishi S, Lee JS, Gardner KE, Gardner JM, Takahashi YH, Chandrasekharan MB, Sun ZW, Osley MA, Strahl BD, Jaspersen SL, Shilatifard A (2009). Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1. J Cell Biol, 186(3), 371-7.
  8. Chandrasekharan MB, Huang F, Sun ZW (2009). Ubiquitination of histone H2B regulates chromatin dynamics by enhancing nucleosome stability. Proc Natl Acad Sci U S A, 106(39), 16686-91.
  9. Bhaskara S, Chandrasekharan MB, Ganguly R (2008). Caffeine induction of Cyp6a2 and Cyp6a8 genes of Drosophila melanogaster is modulated by cAMP and D-JUN protein levels. Gene, 415(1-2), 49-59.
  10. Bradley C, van der Meer R, Roodi N, Yan H, Chandrasekharan MB, Sun ZW, Mernaugh RL, Parl FF (2007). Carcinogen-induced histone alteration in normal human mammary epithelial cells. Carcinogenesis, 28(10), 2184-92.
  11. Ng DW, Chandrasekharan MB, Hall TC (2006). Ordered histone modifications are associated with transcriptional poising and activation of the phaseolin promoter. Plant Cell, 18(1), 119-32.
  12. Zhou X, Chandrasekharan MB, Hall TC (2004). High rooting frequency and functional analysis of GUS and GFP expression in transgenic Medicago truncatula A17. New Phytol, 162, 813-822.
  13. Teerawanichpan P, Chandrasekharan MB, Jiang Y, Narangajavana J, Hall TC (2004). Characterization of two rice DNA methyltransferase genes and RNAi-mediated reactivation of a silenced transgene in rice callus. Planta, 218(3), 337-49.
  14. Grace ML, Chandrasekharan MB, Hall TC, Crowe AJ (2004). Sequence and spacing of TATA box elements are critical for accurate initiation from the beta-phaseolin promoter. J Biol Chem, 279(9), 8102-10.
  15. Ng DW, Chandrasekharan MB, Hall TC (2004). The 5' UTR negatively regulates quantitative and spatial expression from the ABI3 promoter. Plant Mol Biol, 54(1), 25-38.
  16. Carranco R, Chandrasekharan MB, Townsend JC, Hall TC (2004). Interaction of PvALF and VP1 B3 domains with the beta -phaseolin promoter. Plant Mol Biol, 55(2), 221-37.
  17. Chandrasekharan MB, Bishop KJ, Hall TC (2003). Module-specific regulation of the beta-phaseolin promoter during embryogenesis. Plant J, 33(5), 853-66.
  18. Chandrasekharan MB, Li G, Bishop KJ, Hall TC (2003). S phase progression is required for transcriptional activation of the beta-phaseolin promoter. J Biol Chem, 278(46), 45397-405.
  19. Yang G, Dong J, Chandrasekharan MB, Hall TC (2001). Kiddo, a new transposable element family closely associated with rice genes. Mol Genet Genomics, 266(3), 417-24.
  20. Li G, Bishop KJ, Chandrasekharan MB, Hall TC (1999). beta-Phaseolin gene activation is a two-step process: PvALF- facilitated chromatin modification followed by abscisic acid-mediated gene activation. Proc Natl Acad Sci U S A, 96(12), 7104-9.
  21. Hall TC, Li G, Chandrasekharan MB (1998). Participation of chromatin in the regulation of phaseolin gene expression. J Plant Physiol, 152, 614-620.

Review

  1. Chandrasekharan MB, Huang F, Sun ZW (2010). Histone H2B ubiquitination and beyond: Regulation of nucleosome stability, chromatin dynamics and the trans-histone H3 methylation. [Review]. Epigenetics, 5(6), 460-8.
  2. Ng DW, Wang T, Chandrasekharan MB, Aramayo R, Kertbundit S, Hall TC (2007). Plant SET domain-containing proteins: structure, function and regulation. [Review]. Biochim Biophys Acta, 1769(5-6), 316-29.
  3. Li G, Chandrasekharan MB, Wolffe AP, Hall TC (2001). Chromatin structure and phaseolin gene regulation. [Review]. Plant Mol Biol, 46(2), 121-9.
  4. Iyer LM, Kumpatla SP, Chandrasekharan MB, Hall TC (2000). Transgene silencing in monocots. [Review]. Plant Mol Biol, 43(2-3), 323-46.
  5. Kumpatla SP, Chandrasekharan MB, Iyer LM, Li G, Hall TC (1998). Genome intruder scanning and modulation systems and transgene silencing. [Review]. Trends in Plant Science, 3, 97-104.

Book Chapter

  1. Hall TC, Chandrasekharan MB, Li G (1999). Phaseolin: its past, properties, regulation and future. In Casey R, Shewry PR (Eds.), Seed Proteins (pp. 209-240). The Netherlands: Kluwer, Dorderecht.