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

Broadly, our research interests include : 

  1. Insights into structural and functional aspects of histone chaperones involved in the DNA damage repair pathways and their role in rare diseases.
  2. Structure-guided designing of inhibitor molecules against epigenetic enzymes  involved in metabolic disorders in human.
  3. Structural and functional characterization histone ubiquitin ligases in different disease contexts. 

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

  1. Das C, Adhikari S, Bhattacharya A, Chakraborty S, Mondal P, Yadav SS, Adhikary S, Hunt C, Yadav KK, Pandita S, Siddhartha Roy, 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. 
  2. Mondal P, Tiwary N, Sengupta A, Dhang S, Siddhartha Roy, Das C. Epigenetic Reprogramming of the Glucose Metabolic Pathways by the Chromatin Effectors During Cancer. Subcell Biochem. 2022;100:269-336. 
  3. Pandita TK, Hunt CR, Singh V, Adhikary S, Pandita S, Siddhartha Roy, 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.
  4. Adhikary S, Singh V, Choudhari R, Yang B, Adhikari S, Ramos EI, Chaudhuri S, Siddhartha Roy, Gadad SS, Das C. ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation. Cell Death Dis. 2022 Sep 5;13(9):766.
  5. Dalui S, Dasgupta A, Adhikari S, Das C and Siddhartha Roy. 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.
  6. Sengupta I, Mondal P, Sengupta A, Mondal A, Singh V, Adhikari S, Dhang S,  Siddhartha Roy 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.
  7. Dasgupta A, Mondal P, Dalui S, Das C and Siddhartha Roy. Molecular characterization of substrate-induced ubiquitin transfer by UBR7-PHD finger, a newly identified histone H2BK120 ubiquitin ligase. FEBS J. 2022; 289(7):1842-1857. * Editor's Choice Article
  8. Adhikari S, Bhattacharya A, Adhikary S, Singh V, Gadad SS, Siddhartha Roy and Das C (2022). The paradigm of drug resistance in cancer: an epigenetic perspective. Bioscience reports, 42(4), BSR20211812.
  9. Adhikary S, Siddhartha Roy, Chacon J, Gadad SS, Das C. Implications of enhancer transcription and eRNAs in cancer. Cancer Res. 2021 May 20.
  10. Srivastava DK, Gunjan S, Das C, Seshadri V, Siddhartha Roy. Structural insights into histone chaperone Asf1 and its characterization from Plasmodium falciparum. Biochem J. 2021 Mar 12;478(5):1117-1136. *Cover Page Article
  11. 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, Siddhartha Roy, Das C. Suppression of poised oncogenes by ZMYND8 promotes chemo-sensitization. Cell Death Dis. 2020 Dec 15;11(12):1073.
  12. Mukherjee S, Sen S, Adhikary S, Sengupta A, Mandal P, Dasgupta D, Chakrabarti P, Siddhartha Roy, 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.
  13. Mondal P, Sen S, Klein BJ, Tiwary N, Gadad SS, Kutateladze TG, Siddhartha Roy, Das C. TCF19 Promotes Cell Proliferation through Binding to the Histone H3K4me3 Mark. Biochemistry. 2020 Feb 4;59(4):389-399.
  14. 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, Siddhartha Roy, 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.
  15. Sen S, Sanyal S, Srivastava DK, Dasgupta D, Siddhartha Roy, 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.
  16. * Cover Page Article
  17. Basu M, Sengupta I, Khan MW, Srivastava DK, Chakrabarti P, Siddhartha Roy, Das C. Dual histone reader ZMYND8 inhibits cancer cell invasion by positively regulating epithelial genes. Biochem J. 2017; 474(11); 1919-34.
  18. Mukherjee S, Adhikary S, Siddhartha Roy, Das C. Noncoding RNAs as chromatin scaffold of histone modification complexes in cancer. In Cancer and Non-coding RNAs, Translational Epigenetics Series,  (Elsevier). 2017
  19. Adhikary S, Sanyal S, Basu M, Sengupta I, Sen S, Srivastava DK, Siddhartha Roy*, Das C*. Selective Recognition of H3.1K36 dimethylation / H4K16 acetylation facilitates the regulation of ATRA-responsive genes by putative chromatin reader ZMYND8. 
  20. J Biol Chem. 2016; 291(6); 2664-81. (* equal corresponding author)
  21. Sarkar S, Siddiqui AA, Mazumder S, De R, Saha SJ, Banerjee C, Iqbal MS, Adhikari S, Alam A, Siddhartha Roy, 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.
  22. Banerjee A, Sanyal S, Kulkarni KK, Jana K, Siddhartha Roy, 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.
  23. Das C, Siddhartha Roy, 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.
  24. Sharma K, Mukherjee C, Siddhartha Roy, 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.
  25. Musselman CA, Avvakumov N, Watanabe R, Abraham CG, Lalonde ME, Hong Z, Allen C, Siddhartha Roy, 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.
  26. He J., Scott J.L.,Heroux A., Siddhartha Roy, 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.
  27. Lisandra E.W*., Siddhartha Roy*, 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).
  28. Siddhartha Roy, 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.
  29. Hom R.A., Chang P.Y., Siddhartha Roy, 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.
  30. Siddhartha Roy, 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.
  31. Kishore A.H., Vedamurthy B.M., Mantelingu K., Agrawal S., Reddy B.A., Siddhartha Roy, 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.
  32. Mantelingu K., Reddy B.A, Swaminathan V., Kishore A.H., Siddappa N.B., Kumar G.V., Nagashankar G., Natesh N., Siddhartha Roy, 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.
  33. Selvaraj M., Siddhartha Roy, 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.
  34. Selvaraj M., Thamotharon S., Siddhartha Roy 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.
  35. Siddhartha Roy, 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.
  36. Selvaraj M., Singh N.S., Siddhartha Roy, 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.
  37. Sharma A, Thamotharon S., Siddhartha Roy 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.
  38. Siddhartha Roy, 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.
  39. Siddhartha Roy, 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.
  40. Saraswathi N.T., Siddhartha Roy 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.
  41. Siddhartha Roy, 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.
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