Mahesh B. Chandrasekharan

Mahesh B. Chandrasekharan, MS, PhD

Languages spoken: English, Tulu, Tamil, Malayalam, Kannada, Hindi, Telugu

Academic Information

Departments Adjunct - Internal Medicine , Primary - Radiation Oncology

Divisions: Hematology & Hematologic Malignancies

Academic Office Information

mahesh.chandrasekharan@hci.utah.edu

Lab

Dr. Chandrasekharan received his PhD in Biology in 2001 from Texas A&M University, College Station, TX. He then completed a postdoctoral fellowship at Vanderbilt University Medical Center in Nashville, TN. Currently, Dr. Chandrasekharan is an Assistant Professor in the Department of Radiation Oncology and an Adjunct Assistant Professor in the Division of Hematology & Hematological Malignancies within the Department of Internal Medicine. He is also an Investigator at the Huntsman Cancer Institute and a member of the Nuclear Control of Cell Growth and Differentiation program.

Dr. Chandrasekharan’s research focuses on the regulation and functions of epigenetic mechanisms and protein homeostasis, which together control nearly all aspects of organismal and cellular development, often going awry in cancers. He employs yeast, cultured mammalian cells, and mice as model systems for both fundamental and cancer-focused studies. His research utilizes a range of methodologies, including structural, biochemical, genetic, and genomic/proteomic approaches.

As a graduate student, Dr. Chandrasekharan investigated the role of chromatin in the spatio-temporal regulation of gene expression during development. His postdoctoral research focused on the evolutionarily conserved crosstalk between histone H2B monoubiquitination and the methylation of histone H3 at lysines 4 and 79 (H3K4 and H3K79). A significant discovery during his postdoctoral studies was that histone H2B ubiquitination stabilizes the nucleosome. He also identified that the H2B C-terminal helix modulates H3K4 methylation independently of H2B ubiquitination by serving as a ‘docking site’ for Set1-COMPASS, a methyltransferase-containing complex. As an independent investigator, Dr. Chandrasekharan aims to build upon these works to further elucidate the complexities of trans-histone crosstalk between H2B ubiquitination and H3 methylation. His research also delves into the intricacies of protein turnover or homeostasis (proteostasis) through ubiquitin conjugation.

Histone-modifying enzymes, particularly those involved in the aforementioned trans-histone crosstalk, have garnered significant interest due to their implications in various human diseases, including cancers. The link between dysregulated protein homeostasis mechanisms and cancer is also well established, as exemplified by oncogenic mutations in the BRCA1 E3 ubiquitin ligase. Dr. Chandrasekharan’s current research goals are two-fold: First, he seeks to understand the fundamental mechanisms regulating the functions of histone- and protein-modifying enzymes. Second, he aims to leverage insights gained from these studies to better understand disease formation and progression, ultimately contributing to the development of effective cancer therapeutics.

Education History

Undergraduate St. Aloysius College, University of Mangalore
 BS
Graduate Training Madurai Kamaraj University
 MS
Doctoral Training Texas A&M University
 PhD
Fellowship Institute of Developmental and Molecular Biology, Texas A&M University
 Postdoctoral Research Associate
Postdoctoral Fellowship Vanderbilt University School of Medicine
 Postdoctoral Fellow

Selected Publications

Journal Article

  1. Papaioannou D, Urs AP, Buisson R, Petri A, Liu M, Woodward L, Kulkarni R, Weislämle X, Ivashkiv O, Nicolet D, Goda C, Paraskevopoulou V, Bustos Y, Mrózek K, Eisfeld AK, Chandrasekharan MB, Behbehani GK, Kauppinen S, Aifantis I, Singh G, Dorrance AM, Garzon (2026). circPCMTD1: A protein-coding circular RNA that regulates DNA damage response in BCR/ABL1-positive leukemias. Blood,
  2. Wu Y, Manna AK, Li L, Shen Z, Handa H, Chandrasekharan MB, Tantin (2025). Jade1 and the HBO1 histone acetyltransferase complex are spatial-selective cofactors of the pluripotency transcription factor Oct4. The Journal of biological chemistry, 301(12), 110859.
  3. Shen Z, Wu Y, Manna A, Yi C, Cairns BR, Evason KJ, Chandrasekharan MB, Tantin (2024). Oct4 redox sensitivity potentiates reprogramming and differentiation. Genes & development, 38(7-8), 308-321.
  4. Wu Y, Manna AK, Li L, Handa H, Chandrasekharan MB, Tantin (2024). Jade1 and the HBO1 complex are spatial-selective cofactors of Oct4. bioRxiv,
  5. Shukla PK, Radmall KS, Chandrasekharan M (2023). Rapid purification of rabbit immunoglobulins using a single-step, negative-selection chromatography. Protein expression and purification, 207, 106270.
  6. Shukla PK, Bissell JE, Kumar S, Pokhrel S, Palani S, Radmall KS, Obidi O, Parnell TJ, Brasch J, Shrieve DC, Chandrasekharan M (2023). Structure and functional determinants of Rad6-Bre1 subunits in the histone H2B ubiquitin-conjugating complex. Nucleic acids research, 51(5), 2117-2136.
  7. Perovanovic J, Wu Y, Abewe H, Shen Z, Hughes EP, Gertz J, Chandrasekharan MB, Tantin (2023). Oct1 cooperates with the Smad family of transcription factors to promote mesodermal lineage specification. Science signaling, 16(781), eadd5750.
  8. Radmall KS, Shukla PK, Leng AM, Chandrasekharan M (2023). Structure-function analysis of histone H2B and PCNA ubiquitination dynamics using deubiquitinase-deficient strains. Scientific reports, 13(1), 16731.
  9. Shukla PK, Sinha D, Leng AM, Bissell JE, Thatipamula S, Ganguly R, Radmall KS, Skalicky JJ, Shrieve DC, Chandrasekharan M (2022). Mutations of Rad6 E2 ubiquitin-conjugating enzymes at alanine-126 in helix-3 affect ubiquitination activity and decrease enzyme stability. The Journal of biological chemistry, 298(11), 102524.
  10. Leng AM, Radmall KS, Shukla PK, Chandrasekharan M (2022). Quantitative Assessment of Histone H2B Monoubiquitination in Yeast Using Immunoblotting. Methods and protocols, 5(5),
  11. Hess L, Moos V, Lauber AA, Reiter W, Schuster M, Hartl N, Lackner D, Boenke T, Koren A, Guzzardo PM, Gundacker B, Riegler A, Vician P, Miccolo C, Leiter S, Chandrasekharan MB, Vcelkova T, Tanzer A, Jun JQ, Bradner J, Brosch G, Hartl M, Bock C, Bürckstümmer T, Kubicek S, Chiocca S, Bhaskara S, Seiser (2022). A toolbox for class I HDACs reveals isoform specific roles in gene regulation and protein acetylation. PLoS genetics, 18(8), e1010376.
  12. Johnson DP, Chandrasekharan MB, Dutreix M, Bhaskara (2021). Targeting DNA Repair and Chromatin Crosstalk in Cancer Therapy. Cancers, 13(3),
  13. Tan Y, Schneider T, Shukla PK, Chandrasekharan MB, Aravind L, Zhang (2021). Unification and extensive diversification of M/Orf3-related ion channel proteins in coronaviruses and other nidoviruses. Virus evolution, 7(1), veab014.
  14. Meriesh HA, Lerner AM, Chandrasekharan MB, Strahl B (2020). The histone H4 basic patch regulates SAGA-mediated H2B deubiquitination and histone acetylation. The Journal of biological chemistry, 295(19), 6561-6569.
  15. Tiburcio PDB, Locke MC, Bhaskara S, Chandrasekharan MB, Huang L (2020). The neural stem-cell marker CD24 is specifically upregulated in IDH-mutant glioma. Translational oncology, 13(10), 100819.
  16. McCullough LL, Pham TH, Parnell TJ, Connell Z, Chandrasekharan MB, Stillman DJ, Formosa T (2019). Establishment and Maintenance of Chromatin Architecture Are Promoted Independently of Transcription by the Histone Chaperone FACT and H3-K56 Acetylation in Saccharomyces cerevisiae. Genetics, 211(3), 877-892.
  17. Tharkar-Promod S, 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 (2018). 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. Leukemia, 32(1), 49-60.
  18. Sdano MA, Fulcher JM, Palani S, Chandrasekharan MB, Parnell TJ, Whitby FG, Formosa T, Hill C (2017). A novel SH2 recognition mechanism recruits Spt6 to the doubly phosphorylated RNA polymerase II linker at sites of transcription. eLife, 6,
  19. Andrade D, Velinder M, Singer J, Maese L, Bareyan D, Nguyen H, Chandrasekharan MB, Lucente H, McClellan D, Jones D, Sharma S, Liu F, Engel M (2016). SUMOylation Regulates Growth Factor Independence 1 in Transcriptional Control and Hematopoiesis. Molecular and cellular biology, 36(10), 1438-50.
  20. Ramakrishnan S, Pokhrel S, Palani S, Pflueger C, Parnell TJ, Cairns BR, Bhaskara S, Chandrasekharan M (2016). Counteracting H3K4 methylation modulators Set1 and Jhd2 co-regulate chromatin dynamics and gene transcription. Nature communications, 7, 11949.
  21. Huang F, Ramakrishnan S, Pokhrel S, Pflueger C, Parnell TJ, Kasten MM, Currie SL, Bhachech N, Horikoshi M, Graves BJ, Cairns BR, Bhaskara S, Chandrasekharan M (2015). Interaction of the Jhd2 Histone H3 Lys-4 Demethylase with Chromatin Is Controlled by Histone H2A Surfaces and Restricted by H2B Ubiquitination. The Journal of biological chemistry, 290(48), 28760-77.
  22. Johnson DP, Spitz GS, Tharkar S, Quayle SN, Shearstone JR, Jones S, McDowell ME, Wellman H, Tyler JK, Cairns BR, Chandrasekharan MB, Bhaskara (2015). HDAC1,2 inhibition impairs EZH2- and BBAP-mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma. Oncotarget, 6(7), 4863-87.
  23. Bhaskara S, Jacques V, Rusche JR, Olson EN, Cairns BR, Chandrasekharan M (2013). Histone deacetylases 1 and 2 maintain S-phase chromatin and DNA replication fork progression. Epigenetics & chromatin, 6(1), 27.
  24. Joo HY, Jones A, Yang C, Zhai L, Smith AD 4th, Zhang Z, Chandrasekharan MB, Sun ZW, Renfrow MB, Wang Y, Chang C, Wang (2011). Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46. The Journal of biological chemistry, 286(9), 7190-201.
  25. Chandrasekharan MB, Huang F, Sun Z (2011). Decoding the trans-histone crosstalk: methods to analyze H2B ubiquitination, H3 methylation and their regulatory factors. Methods (San Diego, Calif.), 54(3), 304-14.
  26. Huang F, Chandrasekharan MB, Chen YC, Bhaskara S, Hiebert SW, Sun Z (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. The Journal of biological chemistry, 285(32), 24548-61.
  27. Chandrasekharan MB, Huang F, Chen YC, Sun Z (2010). Histone H2B C-terminal helix mediates trans-histone H3K4 methylation independent of H2B ubiquitination. Molecular and cellular biology, 30(13), 3216-32.
  28. 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 S (2010). Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer cell, 18(5), 436-47.
  29. Nakanishi S, Lee JS, Gardner KE, Gardner JM, Takahashi YH, Chandrasekharan MB, Sun ZW, Osley MA, Strahl BD, Jaspersen SL, Shilatifard (2009). Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1. The Journal of cell biology, 186(3), 371-7.
  30. Chandrasekharan MB, Huang F, Sun Z (2009). Ubiquitination of histone H2B regulates chromatin dynamics by enhancing nucleosome stability. Proceedings of the National Academy of Sciences of the United States of America, 106(39), 16686-91.
  31. Bhaskara S, Chandrasekharan MB, Ganguly (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.
  32. 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.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. Grace ML, Chandrasekharan MB, Hall TC, Crowe A (2004). Sequence and spacing of TATA box elements are critical for accurate initiation from the beta-phaseolin promoter. The Journal of biological chemistry, 279(9), 8102-10.
  38. Zhou X, Chandrasekharan MB, Hall T (2004). High rooting frequency and functional analysis of GUS and GFP expression in transgenic Medicago truncatula A17. The New phytologist, 162(3), 813-822.
  39. Chandrasekharan MB, Bishop KJ, Hall TC (2003). Module-specific regulation of the beta-phaseolin promoter during embryogenesis. Plant J, 33(5), 853-66.
  40. Chandrasekharan MB, Li G, Bishop KJ, Hall T (2003). S phase progression is required for transcriptional activation of the beta-phaseolin promoter. The Journal of biological chemistry, 278(46), 45397-405.
  41. Yang G, Dong J, Chandrasekharan MB, Hall T (2001). Kiddo, a new transposable element family closely associated with rice genes. Molecular genetics and genomics, 266(3), 417-24.
  42. Li G, Bishop KJ, Chandrasekharan MB, Hall T (1999). beta-Phaseolin gene activation is a two-step process: PvALF- facilitated chromatin modification followed by abscisic acid-mediated gene activation. Proceedings of the National Academy of Sciences of the United States of America, 96(12), 7104-9.
  43. Hall TC, Li G, Chandrasekharan M (1998). Participation of chromatin in the regulation of phaseolin gene expression. Journal of plant physiology, 152, 614-620.

Review

  1. Chandrasekharan MB, Huang F, Sun Z (2010). Histone H2B ubiquitination and beyond: Regulation of nucleosome stability, chromatin dynamics and the trans-histone H3 methylation. 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 T (1998). Genome intruder scanning and modulation systems and transgene silencing. Trends in plant science, 3, 97-104.

Book Chapter

  1. Hall TC, Chandrasekharan MB, Li (1999). Phaseolin: its past, properties, regulation and future. 209-240.