Siavash Kurdistani*
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.
Websites:
Research Interests:
Functions of histones in biology and disease,Publications:
Tod NP, Vogelauer M, Cheng C, Karimian A, Schmollinger S, Camacho D, Kurdistani SK. The role of histone H3 leucine 126 in fine-tuning the copper reductase activity of nucleosomes. J Biol Chem. 2024 Apr 22; 300(6):107314. view on PubMed
Karimian A, Vogelauer M, Kurdistani SK. Metabolic sinkholes: Histones as methyl repositories. PLoS Biol. 2023 Oct; 21(10):e3002371. view on PubMed
Vogelauer M, Cheng C, Karimian A, Iranpour HG, Kurdistani SK. Zinc is Essential for the Copper Reductase Activity of Yeast Nucleosomes. bioRxiv. 2023 Sep 14. view on PubMed
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. Nat Mater. 2022 10; 21(10):1191-1199. view on PubMed
Cheng C, Kurdistani SK. Chromatin as a metabolic organelle: Integrating the cellular flow of carbon with gene expression. Mol Cell. 2022 01 06; 82(1):8-9. view on PubMed
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. Sci Adv. 2021 Dec 17; 7(51):eabj9889. view on PubMed
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. 2020 07 03; 369(6499):59-64. view on PubMed
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 12; 576(7786):281-286. view on PubMed
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. 2019 09 26; 146(19). view on PubMed
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. Mol Cell. 2019 01 17; 73(2):250-263.e5. view on PubMed
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. 2018 10 05; 362(6410):91-95. view on PubMed
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 12; 6. view on PubMed
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. Mol Cell. 2017 Aug 17; 67(4):594-607.e4. view on PubMed
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. J Biol Chem. 2017 08 11; 292(32):13197-13204. view on PubMed
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 Mar 21; 8(12):19074-19088. view on PubMed
Attar N, Kurdistani SK. Exploitation of EP300 and CREBBP Lysine Acetyltransferases by Cancer. Cold Spring Harb Perspect Med. 2017 Mar 01; 7(3). view on PubMed
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 Dev. 2017 02 01; 31(3):241-246. view on PubMed
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. Nat Commun. 2016 08 10; 7:12376. view on PubMed
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. J Biol Chem. 2016 07 22; 291(30):15428-46. view on PubMed
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 Rep. 2016 Feb 23; 14(7):1590-1601. view on PubMed
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. Mol Cell. 2016 Jan 07; 61(1):27-38. view on PubMed
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 Dev. 2015 Feb 15; 29(4):350-5. view on PubMed
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. EMBO J. 2015 Mar 12; 34(6):759-77. view on PubMed
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 Nov 12; 16(5):663-76. view on PubMed
Kurdistani SK. Chromatin: a capacitor of acetate for integrated regulation of gene expression and cell physiology. Curr Opin Genet Dev. 2014 Jun; 26:53-8. view on PubMed
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 Jun 17; 3. view on PubMed
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 Metab. 2014 Apr 01; 19(4):694-701. view on PubMed
Jazirehi AR, Kurdistani SK, Economou JS. Histone deacetylase inhibitor sensitizes apoptosis-resistant melanomas to cytotoxic human T lymphocytes through regulation of TRAIL/DR5 pathway. J Immunol. 2014 Apr 15; 192(8):3981-9. view on PubMed
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. 2014 Feb; 9(2):257-67. view on PubMed
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. Proc Natl Acad Sci U S A. 2013 Jul 30; 110(31):12655-60. view on PubMed
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 Metab. 2013 Jun 04; 17(6):1000-1008. view on PubMed
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. Mol Cell. 2013 Jan 24; 49(2):310-21. view on PubMed
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 Rep. 2012 Nov 29; 2(5):1061-7. view on PubMed
Li JY, Patterson M, Mikkola HK, Lowry WE, Kurdistani SK. Dynamic distribution of linker histone H1.5 in cellular differentiation. PLoS Genet. 2012; 8(8):e1002879. view on PubMed
Lehmann L, Ferrari R, Vashisht AA, Wohlschlegel JA, Kurdistani SK, Carey M. Polycomb repressive complex 1 (PRC1) disassembles RNA polymerase II preinitiation complexes. J Biol Chem. 2012 Oct 19; 287(43):35784-94. view on PubMed
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 Aug 03; 150(3):590-605. view on PubMed
Vogelauer M, Krall AS, McBrian MA, Li JY, Kurdistani SK. Stimulation of histone deacetylase activity by metabolites of intermediary metabolism. J Biol Chem. 2012 Sep 14; 287(38):32006-16. view on PubMed
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 Res. 2012 Jul; 22(7):1212-21. view on PubMed
Kurdistani SK. Enhancer dysfunction: how the main regulators of gene expression contribute to cancer. Genome Biol. 2012; 13(5):156. view on PubMed
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. Curr Biol. 2012 Jan 10; 22(1):56-63. view on PubMed
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; 6(11):e26894. view on PubMed
Kurdistani SK. Histone modifications in cancer biology and prognosis. Prog Drug Res. 2011; 67:91-106. view on PubMed
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. J Clin Oncol. 2010 Mar 10; 28(8):1358-65. view on PubMed
Ferrari R, Berk AJ, Kurdistani SK. Viral manipulation of the host epigenome for oncogenic transformation. Nat Rev Genet. 2009 05; 10(5):290-4. view on PubMed
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. Am J Pathol. 2009 May; 174(5):1619-28. view on PubMed
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 Apr 09; 113(15):3461-71. view on PubMed
Horwitz GA, Zhang K, McBrian MA, Grunstein M, Kurdistani SK, Berk AJ. Adenovirus small e1a alters global patterns of histone modification. Science. 2008 Aug 22; 321(5892):1084-5. view on PubMed
Ferrari R, Pellegrini M, Horwitz GA, Xie W, Berk AJ, Kurdistani SK. Epigenetic reprogramming by adenovirus e1a. Science. 2008 Aug 22; 321(5892):1086-8. view on PubMed
Peng W, Togawa C, Zhang K, Kurdistani SK. Regulators of cellular levels of histone acetylation in Saccharomyces cerevisiae. Genetics. 2008 May; 179(1):277-89. view on PubMed
Pham H, Ferrari R, Cokus SJ, Kurdistani SK, Pellegrini M. Modeling the regulatory network of histone acetylation in Saccharomyces cerevisiae. Mol Syst Biol. 2007; 3:153. view on PubMed
Kurdistani SK. Histone modifications as markers of cancer prognosis: a cellular view. Br J Cancer. 2007 Jul 02; 97(1):1-5. view on PubMed
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 Nov 18; 123(4):593-605. view on PubMed
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 Jun 30; 435(7046):1262-6. view on PubMed
Kim KT, Ongusaha PP, Hong YK, Kurdistani SK, Nakamura M, Lu KP, Lee SW. Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint. J Biol Chem. 2004 Sep 10; 279(37):38597-602. view on PubMed
Kurdistani SK, Tavazoie S, Grunstein M. Mapping global histone acetylation patterns to gene expression. Cell. 2004 Jun 11; 117(6):721-33. view on PubMed
Millar CB, Kurdistani SK, Grunstein M. Acetylation of yeast histone H4 lysine 16: a switch for protein interactions in heterochromatin and euchromatin. Cold Spring Harb Symp Quant Biol. 2004; 69:193-200. view on PubMed
Robyr D, Kurdistani SK, Grunstein M. Analysis of genome-wide histone acetylation state and enzyme binding using DNA microarrays. Methods Enzymol. 2004; 376:289-304. view on PubMed
Kurdistani SK, Grunstein M. In vivo protein-protein and protein-DNA crosslinking for genomewide binding microarray. Methods. 2003 Sep; 31(1):90-5. view on PubMed
Kurdistani SK, Grunstein M. Histone acetylation and deacetylation in yeast. Nat Rev Mol Cell Biol. 2003 Apr; 4(4):276-84. view on PubMed
Wang A, Kurdistani SK, Grunstein M. Requirement of Hos2 histone deacetylase for gene activity in yeast. Science. 2002 Nov 15; 298(5597):1412-4. view on PubMed
Kurdistani SK, Robyr D, Tavazoie S, Grunstein M. Genome-wide binding map of the histone deacetylase Rpd3 in yeast. Nat Genet. 2002 Jul; 31(3):248-54. view on PubMed
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 May 17; 109(4):437-46. view on PubMed
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. J Biol Chem. 1999 Apr 16; 274(16):11022-9. view on PubMed
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 Res. 1998 Oct 01; 58(19):4439-44. view on PubMed
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; 5(117):1659-1660. view on PubMed
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; 117:1259-1260. view on PubMed
