Siddhartha Roy , Ph.D.

Senior Principal Scientist
Structural Biology & Bioinformatics
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Research Focus

We seek to understand the role of certain macromolecules in the regulation of transcription and chromatin dynamics which crucially impact many fundamental biological processes including development and disease. The ongoing research of the laboratory is focused on dissecting the molecular basis of chromatin organization by means of mediating histone modifications by writer enzymes and histone assembly by histone chaperones - with a combined approach of structural biology, biochemistry, and biophysical approaches.

Research Interest

Our laboratory focuses on advancing our understanding of chromatin biology and epigenetic mechanisms, with particular emphasis on their roles in human disease. Our key research interests include:

  1. Elucidating the structural and functional aspects of histone chaperones in DNA damage repair pathways and investigating their implications in rare genetic disorders.
  2. Small molecule inhibitors that target epigenetic regulatory enzymes implicated in human metabolic disease pathways.
  3. Characterizing the structural features and functional mechanisms of histone ubiquitin ligases across various disease contexts.
  4. Integrating biochemical, cell biology, and structural biology approaches to target human epigenetic reader domain-containing proteins in cancer disease.

Credentials

  • Post-doctoral Research Fellow (2010-2012) MD Anderson Cancer Center, Houston, USA
  • Post-doctoral Research Fellow (2008-2010) University of Colorado Denver, Aurora, USA
  • Ph.D (2007) Indian Institute of Science, Bangalore, India 

Patents & Publications

Selected Publications:

  • Karmakar A, Roy S. Pathogenic variants in the human TONSL protein associated with SPONASTRIME dysplasia impair protein dimerization and DNA repair. Sci Adv. 2026;12(31):eaee1129.
  • ​Srivastava DK, Nandi S, Karmakar A, Das C, Roy S. The chromatin reader ZMYND8 recruits the NuRD component GATAD2A through its MYND domain to regulate MAPT213 long noncoding RNA transcription. J Biol Chem. 2026 May 302(6):111463.​
  • Dhang S, Mondal A, Das C, Roy S. Metformin inhibits the histone methyltransferase CARM1 and attenuates H3 histone methylation during gluconeogenesis. J Biol Chem. 2025 Feb 6:108271.* Cover Page Article
  • Singh V, Mondal A, Adhikary S, Mondal P, Shirgaonkar N, DasGupta R, Roy S, Das C. UBR7 E3 Ligase Suppresses Interferon-β Mediated Immune Signaling by Targeting Sp110 in Hepatitis B Virus-Induced Hepatocellular Carcinoma. ACS Infect Dis. 2024 Nov 8;10(11):3775-3796. 
  • Dasgupta A, Nandi S, Gupta S, Roy S, Das C. To Ub or not to Ub: The epic dilemma of histones that regulate gene expression and epigenetic cross-talk. Biochim Biophys Acta Gene Regul Mech. 2024 Sep;1867(3):195033. 
  • Das C, Bhattacharya A, Adhikari S, Mondal A, Mondal P, Adhikary S, Roy S, Ramos K, Yadav KK, Tainer JA, Pandita TK. A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance. Oncogene. 2024 Jun;43(23):1727-1741.
  • Singh V, Nandi S, Ghosh A, Adhikary S, Mukherjee S, Roy S, Das C. Epigenetic reprogramming of T cells: unlocking new avenues for cancer immunotherapy. Cancer Metastasis Rev. 2024 Mar;43(1):175-195. 
  • Das C, Adhikari S, Bhattacharya A, Chakraborty S, Mondal P, Yadav SS, Adhikary S, Hunt C, Yadav KK, Pandita S, Roy S, Tainer JA, Ahmed Z, Pandita TK. Epigenetic-Metabolic Interplay in the DNA Damage Response and Therapeutic Resistance of Breast Cancer. Cancer Res. 2023 Jan 18:CAN-22-3015. 
  • Mondal P, Tiwary N, Sengupta A, Dhang S, Roy S, Das C. Epigenetic Reprogramming of the Glucose Metabolic Pathways by the Chromatin Effectors During Cancer. Subcell Biochem. 2022;100:269-336. 
  • Pandita TK, Hunt CR, Singh V, Adhikary S, Pandita S, Roy S, Ramos K, Das C. Role of the Histone Acetyl Transferase MOF and the Histone Deacetylase Sirtuins in Regulation of H4K16ac During DNA Damage Repair and Metabolic Programming: Implications in Cancer and Aging. Subcell Biochem. 2022;100:115-141.
  • Adhikary S, Singh V, Choudhari R, Yang B, Adhikari S, Ramos EI, Chaudhuri S, Roy S, Gadad SS, Das C. ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation. Cell Death Dis. 2022 Sep 5;13(9):766.
  • Dalui S, Dasgupta A, Adhikari S, Das C and Roy S. Human testis-specific Y-encoded like protein 5 is a histone H3/H4 specific chaperone which facilitates histone deposition in vitro. J. Biol Chem. 2022 Aug;298(8):102200.
  • Sengupta I, Mondal P, Sengupta A, Mondal A, Singh V, Adhikari S, Dhang S, Roy S and Das C. Epigenetic regulation of Fructose-1, 6-bisphosphatase 1 by host transcription factor Speckled 110 kDa during hepatitis B virus infection. FEBS J. 2022 Nov; 289(21):6694-6713.
  • Dasgupta A, Mondal P, Dalui S, Das C and Roy S. Molecular characterization of substrate-induced ubiquitin transfer by UBR7-PHD finger, a newly identified histone H2BK120 ubiquitin ligase. FEBS J. 2022 Apr; 289(7):1842-1857. * Editor's Choice Article
  • Adhikari S, Bhattacharya A, Adhikary S, Singh V, Gadad SS, Roy S and Das C (2022). The paradigm of drug resistance in cancer: an epigenetic perspective. Bioscience reports, 42(4), BSR20211812
  • Adhikary S, Roy S, Chacon J, Gadad SS, Das C. Implications of enhancer transcription and eRNAs in cancer. Cancer Res. 2021 May 20
  • Srivastava DK, Gunjan S, Das C, Seshadri V, Roy S. Structural insights into histone chaperone Asf1 and its characterization from Plasmodium falciparum. Biochem J. 2021 Mar 12;478(5):1117-1136. * Cover Page Article
  • Mukherjee S, Adhikary S, Gadad SS, Mondal P, Sen S, Choudhari R, Singh V, Adhikari S, Mandal P, Chaudhuri S, Sengupta A, Lakshmanaswamy R, Chakrabarti P, Roy S, Das C. Suppression of poised oncogenes by ZMYND8 promotes chemo-sensitization. Cell Death Dis. 2020 Dec 15;11(12):1073.
  • Mukherjee S, Sen S, Adhikary S, Sengupta A, Mandal P, Dasgupta D, Chakrabarti P, Roy S, Das C. A novel role of tumor suppressor ZMYND8 in inducing differentiation of breast cancer cells through its dual-histone binding function. J Biosci. 2020;45:2.
  • Mondal P, Sen S, Klein BJ, Tiwary N, Gadad SS, Kutateladze TG, Roy S, Das C. TCF19 Promotes Cell Proliferation through Binding to the Histone H3K4me3 Mark. Biochemistry. 2020 Feb 4;59(4):389-399.
  • Adhikary S, Chakravarti D, Terranova C, Sengupta I, Maitituoheti M, Dasgupta A, Srivastava DK, Ma J, Raman AT, Tarco E, Sahin AA, Bassett R, Yang F, Tapia C, Roy S*, Rai K*, Das C*. Atypical plant homeodomain of UBR7 functions as an H2BK120Ub ligase and breast tumor suppressor. Nat Commun. 2019 Mar 28;10(1):1398. (* equal corresponding author)
  • Sen S, Sanyal S, Srivastava DK, Dasgupta D, Roy S, Das C. Transcription factor 19 interacts with histone 3 lysine 4 trimethylation and controls gluconeogenesis via the nucleosome-remodeling-deacetylase complex. J Biol Chem. 2017; 292(50); 20362-78.
    * Cover Page Article
  • Basu M, Sengupta I, Khan MW, Srivastava DK, Chakrabarti P, Roy S, Das C. Dual histone reader ZMYND8 inhibits cancer cell invasion by positively regulating epithelial genes. Biochem J. 2017; 474(11); 1919-34.
  • Mukherjee S, Adhikary S, Roy S, Das C. Noncoding RNAs as chromatin scaffold of histone modification complexes in cancer. In Cancer and Non-coding RNAs, Translational Epigenetics Series,  (Elsevier). 2017
  • Adhikary S, Sanyal S, Basu M, Sengupta I, Sen S, Srivastava DK, Roy S*, Das C*. Selective Recognition of H3.1K36 dimethylation / H4K16 acetylation facilitates the regulation of ATRA-responsive genes by putative chromatin reader ZMYND8. J Biol Chem. 2016; 291(6); 2664-81. (* equal corresponding author)
  • Sarkar S, Siddiqui AA, Mazumder S, De R, Saha SJ, Banerjee C, Iqbal MS, Adhikari S, Alam A, Roy S, Bandyopadhyay U. Ellagic Acid, a Dietary Polyphenol Inhibits Tautomerase Activity of Human Macrophage Migration Inhibitory Factor and Its Pro-inflammatory Responses in Human Peripheral Blood Mononuclear Cells. J Agric Food Chem. 2015;63(20):4988-98.
  • Banerjee A, Sanyal S, Kulkarni KK, Jana K, Roy S, Das C, Dasgupta D. Anticancer drug mithramycin interacts with core histones: An additional mode of action of the DNA groove binder. FEBS Open Bio. 2014; 4:987-95.​
  • Das C, Roy S, Namjoshi S, Malarkey CS, Jones DN, Kutateladze TG, Churchill ME, Tyler JK. Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation. Proc Natl Acad Sci USA. 2014; 111(12):E1072-81.
  • Sharma K, Mukherjee C, Roy S, De D, Bhattacharyya D. Human placental extract mediated inhibition of proteinase K: implications of heparin and glycoproteins in wound physiology. J Cell Physiol. 2014; 229(9):1212-23. 
  • Musselman CA, Avvakumov N, Watanabe R, Abraham CG, Lalonde ME, Hong Z, Allen C, Roy S, Nuñez JK, Nickoloff J, Kulesza CA, Yasui A, Côté J, Kutateladze TG.Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1. Nat Struct Mol Biol. 2012; 19, 1266-1272.
  • He J., Scott J.L.,Heroux A., Roy S, Lenoir M., Overduin M., Stahelin R.V.,Kutateladze T.G.Molecular basis of phosphatidylinositol 4-phosphate and ARF1 GTPase recognition by the FAPP1 pleckstrin homology (PH) domain. J.Biol.Chem. 2011; 286(21); 18650-7.
  • Lisandra E.W*., Roy S*, Weiner K.L., Hayashi R., Shi X., Appella E., Kutateladze T.G., Gozani O.The MBT repeats of L3MBTL1 link set8 mediated p53 methylation at lysine 382 to target gene repression. J.Biol.Chem. 2010; 285(48); 37725-32. (*Authors contributed equally to this work).
  • Roy S, Musselman C.A., Kachirskaia I., Hayashi R., Glass K., Nix J.C., Gozani O., Appella E., Kutateladze T.G.Structural insight into p53 recognition by the 53BP1 tandem Tudor domain. J Mol Biol. 2010; 398(4):489-96.
  • Hom R.A., Chang P.Y., Roy S, Musselman C.A., Glass K.C., Selezneva A.I., Gozani O., Ismagilov R.F., Cleary M.L. and Kutateladze T.G. Molecular Mechanism of MLL PHD3 and RNA Recognition by the Cyp33 RRM Domain. J Mol Biol. 2010; 400(2):145-54.
  • Roy S, Saraswathi R., Sekar K., Chatterji D., and Vijayan M. Structural studies on the second Mycobacterium smegmatis Dps: invariant and variable features of structure, assembly and function.. J Mol Biol. 2008; 375(4):948-59.
  • Kishore A.H., Vedamurthy B.M., Mantelingu K., Agrawal S., Reddy B.A., Roy S, Rangappa K.S. and Kundu T.K. Specific small-molecule activator of Aurora kinase A induces autophosphorylation in a cell-free system. J Med Chem. 2008; 51(4):792-7.
  • Mantelingu K., Reddy B.A, Swaminathan V., Kishore A.H., Siddappa N.B., Kumar G.V., Nagashankar G., Natesh N., Roy S, Sadhale P.P., Ranga U., Narayana.C, and Kundu T.K. Specific inhibition of p300-HAT alters global gene expression and represses HIV replication. Chem Biol. 2007; 14(6):645-57
  • Selvaraj M., Roy S, Singh N.S., Sangeetha R., Varshney U. and Vijayan M. Structural plasticity and enzyme action: crystal structures of mycobacterium tuberculosis peptidyl-tRNA hydrolase. J Mol Biol. 2007; 372(1):186-93.
  • Selvaraj M., Thamotharon S., Roy S and Vijayan M. “X-ray studies of crystalline complexes involving amino acids and peptides. XLIV. Invariant features of supramolecular association and chiral effects in the complexes of arginine and lysine with tartaric acid.” ActaCrystallogrB. 2007; 459-68.
  • Roy S, Saraswathi R., Gupta S., Sekar K., Chatterji D. and Vijayan M. Role of N- and C-terminal tails in DNA binding and assembly in Dps. Structural studies of Mycobacterium smegmatisDps deletion mutants. J Mol Biol. 2007; 370(4):752-67.
  • Selvaraj M., Singh N.S., Roy S, Sangeetha R., Varshney U. and Vijayan M. “Cloning, expression, purification, crystallization and preliminary X-ray analysis of PeptidyltRNA hydrolase from Mycobacterium tuberculosis” ActaCryst(2006). F62, 913-915.
  • Sharma A, Thamotharon S., Roy S and Vijayan M. “X-ray studies of crystalline complexes involving amino acids and peptides.XLI II.Adipic acid complexes of L- and DL-Lysine”. ActaCryst(2006).C62,o148-o152.
  • Roy S, Singh D.D., and Vijayan M. “X-ray studies on crystalline complexes involving amino acids and peptides.XLI. Adipic acid complexes of L-and DL-arginine and supramolecular association in arginine-dicarboxylic acid complexes”. ActaCryst(2005) B61, 89-95.
  • Roy S, Gupta S., Das S., Sekar K, Chatterji D. and Vijayan M. “X-ray analysis of Mycobacterium smegmatis Dps and a comparative study involving other Dps and Dps-like molecules”. J.Mol.Biol (2004) 339(5), 1103-1113.
  • Saraswathi N.T., Roy S and Vijayan M. “X-ray studies on crystalline complexes involving amino acids and peptides.XLI. Commonalities in aggregation and conformation revealed by the crystal structures of the pimelic acid complexes of L-arginine and DL-lysine”. ActaCryst(2003) B59, 641-646.
  • Roy S, Gupta S., Das S., Sekar K., Chatterji D., and Vijayan M. “Crystallization and preliminary X-ray diffraction analysis of Mycobacterium smegmatisDps”. ActaCryst(2003) D59,2254-2256.

 

For a complete list of publications:

https://www.ncbi.nlm.nih.gov/myncbi/siddhartha.roy.7/bibliography/public/

 

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