Siavash K Kurdistani

Department Chair, Biological Chemistry, University of California Los Angeles

Professor, Biological Chemistry, University of California Los Angeles

Professor, Pathology and Laboratory Medicine, University of California Los Angeles

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Our laboratory investigates the functions of histones in regulation of specific biological processes and their alterations in human disease using biochemical, genetic, molecular biological and high-throughput approaches. Although we are agnostic to model systems, we choose and employ one that is most appropriate for the question being asked. Presently, we use cancer cell lines, human and murine embryonic stem cells, primary human cancer tissues as well as the model organism, Saccharomyces cerevisiae, to study the basic biology and pathophysiology of histones. We seek and welcome collaborations that will mutually enrich and enhance research by expanding technical and intellectual repertoire. Our mission is to cultivate a culture of intellectual curiosity and experimental exploration unencumbered by perceived dogma. We take deliberate risks to enable inquiry into uncharted territories, yet practice within our scientific space in order to incur the funds necessary to move forward with our unique vision and speculations. We encourage imaginative, inspired and original thinking that produce new scientific narratives devoid of hyperbole and cynicism. As students of life sciences, we are enamored by the biology of chromatin and feel privileged to explore the perplexity of its structure for the pure joy of discovery and the betterment of society.

Interests

Functions of histones in biology and disease

Education and Training

David Geffen School of Medicine at UCLAPostdoc08/2004Chromatin Biology
David Geffen School of Medicine at UCLAIntern06/2000Pathology Internship
Havard Medical SchoolMD06/1999Medicine
University of California, Los Angeles (UCLA)BS06/1994Biochemistry
Santa Monica CollegeAA06/1991

Awards and Honors

  • Harvard National Scholarship, Harvard Medical School, 1994-96.
  • Howard Hughes Medical Institute Early Career Award, Howard Hughes Medical Institute, 2006-2009.
  • Howard Hughes Medical Institute Research Fellowship, Howard Hughes Medical Institute, 1996-1999.
  • NIH Director's Innovator Award, National Institutes of Health, 2009.
  • The Arthur Furst Award, UCLA Department of Chemistry and Biochemistry, 1994.
  • Lucy Wortham James Medical Student Research Award, Havard Medical School, 1995.
  • James Tolbert Shipely Prize, Harvard Medical School, 1999.
  • Elected to the American Society for Clinical Investigation (ASCI), American Society for Clinical Investigation (ASCI), 2019.
  • W. M. Keck Foundation Research Award, W. M. Keck Foundation, 2018.
  • Chancellor's Award for Postdoctoral Fellows, UCLA, 2003.
  • Beckman Young Investigator Award, Arnold and Mabel Beckman Foundation, 2007.
  • Kavli Fellow, The Kavli Foundation, 2011.
  • Alumni Association Distinguished Scholars Award, UCLA, 1992.
  • College of Letters & Science Scholar Award, UCLA, 1993.
  • Postdoctoral Research Fellowship for Physicians, Howard Hughes Medical Institute, 2001-2004.

Publications

  1. Karimian A, Vogelauer M, Kurdistani SK. Metabolic sinkholes: Histones as methyl repositories.. PLoS biology, 2023.
  2. Vogelauer M, Cheng C, Karimian A, Iranpour HG, Kurdistani SK. Zinc is Essential for the Copper Reductase Activity of Yeast Nucleosomes.. bioRxiv : the preprint server for biology, 2023.
  3. Song Y, Soto J, Chen B, Hoffman T, Zhao W, Zhu N, Peng Q, Liu L, Ly C, Wong PK, Wang Y, Rowat AC, Kurdistani SK, Li S. Transient nuclear deformation primes epigenetic state and promotes cell reprogramming.. Nature materials, 2022.
  4. Cheng C, Kurdistani SK. Chromatin as a metabolic organelle: Integrating the cellular flow of carbon with gene expression.. Molecular cell, 2022.
  5. Campos OA, Attar N, Cheng C, Vogelauer M, Mallipeddi NV, Schmollinger S, Matulionis N, Christofk HR, Merchant SS, Kurdistani SK. A pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich's ataxia.. Science advances, 2021.
  6. Attar N, Campos OA, Vogelauer M, Cheng C, Xue Y, Schmollinger S, Salwinski L, Mallipeddi NV, Boone BA, Yen L, Yang S, Zikovich S, Dardine J, Carey MF, Merchant SS, Kurdistani SK. The histone H3-H4 tetramer is a copper reductase enzyme.. Science (New York, N.Y.), 2020.
  7. Calvanese V, Nguyen AT, Bolan TJ, Vavilina A, Su T, Lee LK, Wang Y, Lay FD, Magnusson M, Crooks GM, Kurdistani SK, Mikkola HKA. MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment.. Nature, 2019.
  8. Drinnenberg IA, Berger F, Elsässer SJ, Andersen PR, Ausió J, Bickmore WA, Blackwell AR, Erwin DH, Gahan JM, Gaut BS, Harvey ZH, Henikoff S, Kao JY, Kurdistani SK, Lemos B, Levine MT, Luger K, Malik HS, Martín-Durán JM, Peichel CL, Renfree MB, Rutowicz K, Sarkies P, Schmitz RJ, Technau U, Thornton JW, Warnecke T, Wolfe KH. EvoChromo: towards a synthesis of chromatin biology and evolution.. Development (Cambridge, England), 2019.
  9. Sun F, Chronis C, Kronenberg M, Chen XF, Su T, Lay FD, Plath K, Kurdistani SK, Carey MF. Promoter-Enhancer Communication Occurs Primarily within Insulated Neighborhoods.. Molecular cell, 2018.
  10. Park JW, Lee JK, Sheu KM, Wang L, Balanis NG, Nguyen K, Smith BA, Cheng C, Tsai BL, Cheng D, Huang J, Kurdistani SK, Graeber TG, Witte ON. Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage.. Science (New York, N.Y.), 2018.
  11. Nakano H, Minami I, Braas D, Pappoe H, Wu X, Sagadevan A, Vergnes L, Fu K, Morselli M, Dunham C, Ding X, Stieg AZ, Gimzewski JK, Pellegrini M, Clark PM, Reue K, Lusis AJ, Ribalet B, Kurdistani SK, Christofk H, Nakatsuji N, Nakano A. Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis.. eLife, 2017.
  12. Xue Y, Pradhan SK, Sun F, Chronis C, Tran N, Su T, Van C, Vashisht A, Wohlschlegel J, Peterson CL, Timmers HTM, Kurdistani SK, Carey MF. Mot1, Ino80C, and NC2 Function Coordinately to Regulate Pervasive Transcription in Yeast and Mammals.. Molecular cell, 2017.
  13. Xue Y, Schmollinger S, Attar N, Campos OA, Vogelauer M, Carey MF, Merchant SS, Kurdistani SK. Endoplasmic reticulum-mitochondria junction is required for iron homeostasis.. The Journal of biological chemistry, 2017.
  14. Nguyen AH, Elliott IA, Wu N, Matsumura C, Vogelauer M, Attar N, Dann A, Ghukasyan R, Toste PA, Patel SG, Williams JL, Li L, Dawson DW, Radu C, Kurdistani SK, Donahue TR. Histone deacetylase inhibitors provoke a tumor supportive phenotype in pancreatic cancer associated fibroblasts.. Oncotarget, 2017.
  15. Attar N, Kurdistani SK. Exploitation of EP300 and CREBBP Lysine Acetyltransferases by Cancer.. Cold Spring Harbor perspectives in medicine, 2017.
  16. Huang C, Su T, Xue Y, Cheng C, Lay FD, McKee RA, Li M, Vashisht A, Wohlschlegel J, Novitch BG, Plath K, Kurdistani SK, Carey M. Cbx3 maintains lineage specificity during neural differentiation.. Genes & development, 2017.
  17. Wang W, Org T, Montel-Hagen A, Pioli PD, Duan D, Israely E, Malkin D, Su T, Flach J, Kurdistani SK, Schiestl RH, Mikkola HK. MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis.. Nature communications, 2016.
  18. Monte E, Rosa-Garrido M, Karbassi E, Chen H, Lopez R, Rau CD, Wang J, Nelson SF, Wu Y, Stefani E, Lusis AJ, Wang Y, Kurdistani SK, Franklin S, Vondriska TM. Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION.. The Journal of biological chemistry, 2016.
  19. Hong CS, Graham NA, Gu W, Espindola Camacho C, Mah V, Maresh EL, Alavi M, Bagryanova L, Krotee PAL, Gardner BK, Behbahan IS, Horvath S, Chia D, Mellinghoff IK, Hurvitz SA, Dubinett SM, Critchlow SE, Kurdistani SK, Goodglick L, Braas D, Graeber TG, Christofk HR. MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4.. Cell reports, 2016.
  20. Pradhan SK, Su T, Yen L, Jacquet K, Huang C, Côté J, Kurdistani SK, Carey MF. EP400 Deposits H3.3 into Promoters and Enhancers during Gene Activation.. Molecular cell, 2015.
  21. Xue Y, Van C, Pradhan SK, Su T, Gehrke J, Kuryan BG, Kitada T, Vashisht A, Tran N, Wohlschlegel J, Peterson CL, Kurdistani SK, Carey MF. The Ino80 complex prevents invasion of euchromatin into silent chromatin.. Genes & development, 2015.
  22. Org T, Duan D, Ferrari R, Montel-Hagen A, Van Handel B, Kerényi MA, Sasidharan R, Rubbi L, Fujiwara Y, Pellegrini M, Orkin SH, Kurdistani SK, Mikkola HK. Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence.. The EMBO journal, 2015.
  23. Ferrari R, Gou D, Jawdekar G, Johnson SA, Nava M, Su T, Yousef AF, Zemke NR, Pellegrini M, Kurdistani SK, Berk AJ. Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection.. Cell host & microbe, 2014.
  24. Kurdistani SK. Chromatin: a capacitor of acetate for integrated regulation of gene expression and cell physiology.. Current opinion in genetics & development, 2014.
  25. Macadangdang BR, Oberai A, Spektor T, Campos OA, Sheng F, Carey MF, Vogelauer M, Kurdistani SK. Evolution of histone 2A for chromatin compaction in eukaryotes.. eLife, 2014.
  26. Thai M, Graham NA, Braas D, Nehil M, Komisopoulou E, Kurdistani SK, McCormick F, Graeber TG, Christofk HR. Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.. Cell metabolism, 2014.
  27. Jazirehi AR, Kurdistani SK, Economou JS. Histone deacetylase inhibitor sensitizes apoptosis-resistant melanomas to cytotoxic human T lymphocytes through regulation of TRAIL/DR5 pathway.. Journal of immunology (Baltimore, Md. : 1950), 2014.
  28. Li B, Su T, Ferrari R, Li JY, Kurdistani SK. A unique epigenetic signature is associated with active DNA replication loci in human embryonic stem cells.. Epigenetics, 2013.
  29. Cherrier T, Le Douce V, Eilebrecht S, Riclet R, Marban C, Dequiedt F, Goumon Y, Paillart JC, Mericskay M, Parlakian A, Bausero P, Abbas W, Herbein G, Kurdistani SK, Grana X, Van Driessche B, Schwartz C, Candolfi E, Benecke AG, Van Lint C, Rohr O. CTIP2 is a negative regulator of P-TEFb.. Proceedings of the National Academy of Sciences of the United States of America, 2013.
  30. Babic I, Anderson ES, Tanaka K, Guo D, Masui K, Li B, Zhu S, Gu Y, Villa GR, Akhavan D, Nathanson D, Gini B, Mareninov S, Li R, Camacho CE, Kurdistani SK, Eskin A, Nelson SF, Yong WH, Cavenee WK, Cloughesy TF, Christofk HR, Black DL, Mischel PS. EGFR mutation-induced alternative splicing of Max contributes to growth of glycolytic tumors in brain cancer.. Cell metabolism, 2013.
  31. McBrian MA, Behbahan IS, Ferrari R, Su T, Huang TW, Li K, Hong CS, Christofk HR, Vogelauer M, Seligson DB, Kurdistani SK. Histone acetylation regulates intracellular pH.. Molecular cell, 2012.
  32. Chen XF, Lehmann L, Lin JJ, Vashisht A, Schmidt R, Ferrari R, Huang C, McKee R, Mosley A, Plath K, Kurdistani SK, Wohlschlegel J, Carey M. Mediator and SAGA have distinct roles in Pol II preinitiation complex assembly and function.. Cell reports, 2012.
  33. Li JY, Patterson M, Mikkola HK, Lowry WE, Kurdistani SK. Dynamic distribution of linker histone H1.5 in cellular differentiation.. PLoS genetics, 2012.
  34. Lehmann L, Ferrari R, Vashisht AA, Wohlschlegel JA, Kurdistani SK, Carey M. Polycomb repressive complex 1 (PRC1) disassembles RNA polymerase II preinitiation complexes.. The Journal of biological chemistry, 2012.
  35. Van Handel B, Montel-Hagen A, Sasidharan R, Nakano H, Ferrari R, Boogerd CJ, Schredelseker J, Wang Y, Hunter S, Org T, Zhou J, Li X, Pellegrini M, Chen JN, Orkin SH, Kurdistani SK, Evans SM, Nakano A, Mikkola HK. Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium.. Cell, 2012.
  36. Vogelauer M, Krall AS, McBrian MA, Li JY, Kurdistani SK. Stimulation of histone deacetylase activity by metabolites of intermediary metabolism.. The Journal of biological chemistry, 2012.
  37. Ferrari R, Su T, Li B, Bonora G, Oberai A, Chan Y, Sasidharan R, Berk AJ, Pellegrini M, Kurdistani SK. Reorganization of the host epigenome by a viral oncogene.. Genome research, 2012.
  38. Kurdistani SK. Enhancer dysfunction: how the main regulators of gene expression contribute to cancer.. Genome biology, 2012.
  39. Chen XF, Kuryan B, Kitada T, Tran N, Li JY, Kurdistani S, Grunstein M, Li B, Carey M. The Rpd3 core complex is a chromatin stabilization module.. Current biology : CB, 2011.
  40. Marban C, Su T, Ferrari R, Li B, Vatakis D, Pellegrini M, Zack JA, Rohr O, Kurdistani SK. Genome-wide binding map of the HIV-1 Tat protein to the human genome.. PloS one, 2011.
  41. Kurdistani SK. Histone modifications in cancer biology and prognosis.. Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques, 2011.
  42. Manuyakorn A, Paulus R, Farrell J, Dawson NA, Tze S, Cheung-Lau G, Hines OJ, Reber H, Seligson DB, Horvath S, Kurdistani SK, Guha C, Dawson DW. Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma: results from RTOG 9704.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2010.
  43. Ferrari R, Berk AJ, Kurdistani SK. Viral manipulation of the host epigenome for oncogenic transformation.. Nature reviews. Genetics, 2009.
  44. Seligson DB, Horvath S, McBrian MA, Mah V, Yu H, Tze S, Wang Q, Chia D, Goodglick L, Kurdistani SK. Global levels of histone modifications predict prognosis in different cancers.. The American journal of pathology, 2009.
  45. Gekas C, Rhodes KE, Gereige LM, Helgadottir H, Ferrari R, Kurdistani SK, Montecino-Rodriguez E, Bassel-Duby R, Olson E, Krivtsov AV, Armstrong S, Orkin SH, Pellegrini M, Mikkola HK. Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis.. Blood, 2009.
  46. Horwitz GA, Zhang K, McBrian MA, Grunstein M, Kurdistani SK, Berk AJ. Adenovirus small e1a alters global patterns of histone modification.. Science (New York, N.Y.), 2008.
  47. Ferrari R, Pellegrini M, Horwitz GA, Xie W, Berk AJ, Kurdistani SK. Epigenetic reprogramming by adenovirus e1a.. Science (New York, N.Y.), 2008.
  48. Peng W, Togawa C, Zhang K, Kurdistani SK. Regulators of cellular levels of histone acetylation in Saccharomyces cerevisiae.. Genetics, 2008.
  49. Pham H, Ferrari R, Cokus SJ, Kurdistani SK, Pellegrini M. Modeling the regulatory network of histone acetylation in Saccharomyces cerevisiae.. Molecular systems biology, 2007.
  50. Kurdistani SK. Histone modifications as markers of cancer prognosis: a cellular view.. British journal of cancer, 2007.
  51. Keogh MC, Kurdistani SK, Morris SA, Ahn SH, Podolny V, Collins SR, Schuldiner M, Chin K, Punna T, Thompson NJ, Boone C, Emili A, Weissman JS, Hughes TR, Strahl BD, Grunstein M, Greenblatt JF, Buratowski S, Krogan NJ. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.. Cell, 2005.
  52. Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M, Kurdistani SK. Global histone modification patterns predict risk of prostate cancer recurrence.. Nature, 2005.
  53. Kim KT, Ongusaha PP, Hong YK, Kurdistani SK, Nakamura M, Lu KP, Lee SW. Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint.. The Journal of biological chemistry, 2004.
  54. Kurdistani SK, Tavazoie S, Grunstein M. Mapping global histone acetylation patterns to gene expression.. Cell, 2004.
  55. Millar CB, Kurdistani SK, Grunstein M. Acetylation of yeast histone H4 lysine 16: a switch for protein interactions in heterochromatin and euchromatin.. Cold Spring Harbor symposia on quantitative biology, 2004.
  56. Robyr D, Kurdistani SK, Grunstein M. Analysis of genome-wide histone acetylation state and enzyme binding using DNA microarrays.. Methods in enzymology, 2004.
  57. Kurdistani SK, Grunstein M. In vivo protein-protein and protein-DNA crosslinking for genomewide binding microarray.. Methods (San Diego, Calif.), 2003.
  58. Kurdistani SK, Grunstein M. Histone acetylation and deacetylation in yeast.. Nature reviews. Molecular cell biology, 2003.
  59. Wang A, Kurdistani SK, Grunstein M. Requirement of Hos2 histone deacetylase for gene activity in yeast.. Science (New York, N.Y.), 2002.
  60. Kurdistani SK, Robyr D, Tavazoie S, Grunstein M. Genome-wide binding map of the histone deacetylase Rpd3 in yeast.. Nature genetics, 2002.
  61. Robyr D, Suka Y, Xenarios I, Kurdistani SK, Wang A, Suka N, Grunstein M. Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases.. Cell, 2002.
  62. Reimer CL, Borras AM, Kurdistani SK, Garreau JR, Chung M, Aaronson SA, Lee SW. Altered regulation of cyclin G in human breast cancer and its specific localization at replication foci in response to DNA damage in p53+/+ cells.. The Journal of biological chemistry, 1999.
  63. Kurdistani SK, Arizti P, Reimer CL, Sugrue MM, Aaronson SA, Lee SW. Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage.. Cancer research, 1998.
  64. Kurdistani SK, Helgeson RC, and Cram DJ.. Stepwise shell closures provide hosts that expose or protect guests from outer phase reactants. J. Am. Chem. Soc., 1995.
  65. Kurdistani, SK, Robbins TA, Cram DJ. Comparisons of activation energies for dimethyl sulfoxide rotations in the inner phase of seven carcerands. J. Chem. Soc., Chem. Commun., 1995.