Stephen T. Smale, Ph.D.

Distinguished Professor

310-206-4777

6-730 MRL 675 Charles E. Young Drive South

Website

Affiliations
Vice Dean for Research, David Geffen School of Medicine at UCLA
Distinguished Professor, Microbiology, Immunology & Molecular Genetics
Sherie L. and Donald G. Morrison Chair, Molecular Immunology

Research Interests
The research in our laboratory is diverse and revolves around our interests in gene regulation, molecular immunology, stem cell biology, and oncogenesis/leukemogenesis. One major area of interest is the molecular mechanisms of pro-inflammatory gene regulation, with an emphasis on transcriptional cascades induced by inflammatory stimuli and the contributions of chromatin structure to the selective regulation of pro-inflammatory genes. A second interest is the selective functions of the five members of the NF-κB family of transcription factors. We also study the mechanisms by which Ikaros family proteins regulate lymphocyte development and leukemogenesis, and the mechanisms by which developmentally regulated genes acquire competence for transcriptional activation in embryonic stem cells and induced pluripotent stem cells.

Biography
Stephen T. Smale is a molecular immunologist and biochemist who arrived at UCLA in 1990 as an Assistant Professor in the Department of Microbiology and Immunology within the UCLA School of Medicine. In 1999, he was promoted to Professor and, in 2014, to Distinguished Professor, in the Department of Microbiology, Immunology, and Molecular Genetics, which spans the UCLA College of Letters and Science and the David Geffen School of Medicine. From 1990 to 2007, he was also a Howard Hughes Medical Institute Investigator. Dr. Smale graduated Magna Cum Laude from Cornell University, with Honors and Distinction in Chemistry. He received his Ph.D. in Biochemistry from the University of California, Berkeley under the mentorship of Dr. Robert Tjian. He then was a Helen Hay Whitney Foundation postdoctoral fellow with Nobelist Dr. David Baltimore at the Whitehead Institute, MIT. At UCLA, Dr. Smale previously served as Vice Chair of the Department of Microbiology, Immunology, and Molecular Genetics, Director of Basic and Translational Research for the UCLA Jonsson Comprehensive Cancer Center, Director of the Howard Hughes Medical Institute Science Education Program, Co-Director of the UCLA-Caltech Medical Scientist Training Program, and founding Chair of the School of Medicine’s Research Initiative in Immunity, Inflammation, infection, and Transplantation (I3T). He currently serves as Vice Dean for Research in the David Geffen School of Medicine. The research in Dr. Smale’s laboratory focuses on gene regulation during inflammatory and innate immune responses and during lymphocyte development and leukemogenesis.

Publications

Tong AJ, Liu X, Thomas BJ, Lissner MM, Baker MR, Senagolage MD, Allred AL, Barish GD, Smale ST A stringent systems approach uncovers gene-specific mechanisms regulating inflammation. Cell. 2016; 165: 165-179.
Arenzana TL, Schjerven H, Smale ST Regulation of gene expression dynamics during developmental transitions by the Ikaros transcription factor. Genes & Dev. 2015; 29: 1801-1816.
Lissner ML, Thomas BJ, Wee K, Tong AJ, Kollmann TR, Smale ST Age-related gene expression differences in monocytes from human neonates, young adults, and older adults. PLoS One 2015; 10: e0132061.
Smale ST, Tarakhovsky A, Natoli G Chromatin contributions to the regulation of innate immunity. Annual Review of Immunology. 2014; 32: 489-911.
Smale ST Transcriptional regulation in the immune system: a status report. Trends Immunol. 2014; 35: 190-194.
Schjerven H, McLaughlin J, Arenzana TL, Frietze S, Cheng D, Wadsworth SE, Lawson GW, Bensinger SJ, Farnham PJ, Witte ON, Smale ST Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros. Nature Immunol. 2013; 14: 1073-1083.
Smale ST, Plevy SE, Weinmann AS, Zhou L, Ramirez-Carrozzi VR, Pope SD, Bhatt DM, Tong AJ Toward an understanding of the gene-specific and global logic of inducible gene transcription. Cold Spring Harb Symp Quant Biol. 2013; 78: 61-68.
Bhatt DM, Pandya-Jones A, Tong AJ, Barozzi I, Lissner MM, Natoli G, Black DL, Smale ST Transcript dynamics of pro inflammatory genes revealed by sequence analysis of subcellular RNA fractions . Cell. 2012; 150: 279-290.
Xu J, Smale ST Designing an enhancer landscape. Cell. 2012; 151: 929-931.
Murray PJ, Smale ST Restraint of inflammatory signaling by interdependent strata of negative regulatory pathways.Nature Immunol. 2012; 13: 916-924.
Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, Matsuki K, Miki S, Doi T, Aderem A, Nishio J, Smale ST, Honda K, Taniguchi T Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nature Immunol. 2012; 13: 659-666.
Siggers T, Chang AB, Teixeira A, Wong D, Williams KJ, Ahmed B, Ragoussis J, Udalova IA, Smale ST, Bulyk ML Principles of dimer-specific gene regulation revealed by a comprehensive characterization of NF-kB family DNA binding. Nature Immunol. 2011; 13: 95-102.
Smale ST Hierarchies of NF-kB target-gene regulation.Nature Immunol. 2011; 12: 689-694.
Smale ST Selective transcription in response to an inflammatory stimulus. Cell. 2010; 140: 833-844.
Smale ST Seq-ing LPS-induced enhancers. Immunity 2010; 32: 296-297.
Ramirez-Carrozzi VR, Braas D, Bhatt DM, Cheng CS, Hong C, Doty KR, Black JC, Hoffmann A, Carey M, Smale ST A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell. 2009; 138: 114-128.
Xu J, Watts JA, Pope SD, Gadue P, Kamps M, Plath K, Zaret KS, Smale ST Transcriptional competence and the active marking of tissue-specific enhancers by defined transcription factors in embryonic and induced pluripotent stem cells . Genes & Dev. 2009; 23: 2824-2838.
Carey M, Peterson CL, and Smale ST Transcriptional regulation in eukaryotes: Concepts, strategies, and techniques, Second edition. 2009; Cold Spring Harbor Laboratory Press: .
Smale ST, Dorshkind K Hematopoiesis flies high with Ikaros. Nature Immunol. 2006; 7: 367-369.
Li CC, Ramirez-Carrozzi VR, Smale ST Pursuing global gene regulation “logic” via RNA interference and chromatin immunoprecipitation. Nature Immunol. 2006; 7: 692-697.
Ramirez-Carrozzi VR, Nazarian AA, Li CC, Gore SL, Sridharan R, Imbalzano AN, Smale ST Selective and antagonistic functions of SWI/SNF and Mi-2b nucleosome remodeling complexes during an inflammatory response.Genes & Dev. 2006; 20: 282-296.
Sanjabi S, Williams KJ, Saccani S, Zhou L, Hoffmann A, Ghosh G, Gerondakis S, Natoli G, Smale ST A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation. Genes & Dev. 2005; 19: 2138-2151.
Su RC, Brown KE, Saaber S, Fisher AG, Merkenschlager M, Smale ST Dynamic assembly of silent chromatin during thymocyte maturation. Nature Genetics. 2004; 36: 502-506.
Smale ST A Th2 cytokine LCR. Adding a new piece to the regulatory puzzle. Immunity. 2003; 19: 1-2.
Smale ST The establishment and maintenance of lymphocyte identity through gene silencing. Nature Immunol. 2003; 4: 607-615.
Papathanasiou P, Perkins AC, Cobb BS, Ferrini R, Sridharan R, Hoyne GF, Nelms KA, Smale ST, Goodnow CC Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the Ikaros transcription factor. Immunity. 2003; 19: 131-144.
Smale ST, Kadonaga JT The RNA polymerase II core promoter. Annual Review of Biochemistry. 2003; 72: 449-479.
McCarty AS, Kleiger G, Eisenberg D, Smale ST Selective dimerization of a C2H2 zinc finger subfamily. Molecular Cell. 2003; 11: 459-470.
Dovat S, Ronni T, Russell D, Ferrini R, Cobb BS, Smale ST A common mechanism for mitotic inactivation of C2H2 zinc finger DNA-binding domains. Genes & Dev. 2002; 16: 2985-2990.
Smale ST and Fisher AG Chromatin structure and gene regulation in the immune system. Annual Review of Immunology. 2002; 20: 427-462.
Smale ST Core promoters: active contributors to combinatorial gene regulation. Genes & Dev. 2001; 15: 2503-2508.
Trinh LA, Ferrini R, Cobb BS, Weinmann AS, Hahm K, Ernst P, Garraway IP, Merkenschlager M, Smale ST Down-regulation of TDT transcription in CD4(+)CD8(+) thymocytes by Ikaros proteins in direct competition with an Ets activator. Genes & Dev. 2001; 15: 1817-1832.
Weinmann AS, Mitchell DM, Sanjabi S, Bradley MN, Hoffmann A, Liou HC, Smale ST Nucleosome remodeling at the IL-12 p40 promoter is a TLR-dependent, Rel-independent event. Nature Immunol. 2001; 2: 51-57.
Cobb BS, Morales-Alcelay S, Kleiger G, Brown KE, Fisher AG, Smale ST Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding. Genes & Dev. 2000; 14: 2146-2160.
Carey M and Smale ST Transcriptional regulation in eukaryotes: Concepts, strategies, and techniques. 2000; Cold Spring Harbor Laboratory Press: .
Weinmann AS, Plevy SE, Smale ST Rapid and selective remodeling of a positioned nucleosome during the induction of IL-12 p40 transcription. Immunity. 1999; 11: 665-675.
Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT, Bleharski JR, Maitland M, Norgard MV, Plevy SE, Smale ST, Brennan PJ, Bloom BR, Godowski PJ, Modlin RL Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science. 1999; 285: 732-736.
Ernst P, Hahm K, Cobb BS, Brown KE, Trinh LA, McCarty AS, Merkenschlager M, Klug CA, Fisher AG, Smale ST Mechanisms of transcriptional regulation in lymphocyte progenitors: insight from an analysis of the terminal transferase promoter. Cold Spr Harb Symp Quant Biol. 1999; 64: 87-97.
Hahm K, Cobb BS, McCarty AS, Brown KE, Klug CA, Lee R, Akashi K, Weissman IL, Fisher AG, and Smale ST Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin. Genes & Dev. 1998; 12: 782-796.
Smale ST, Jain A, Kaufmann J, Emami KH, Lo K, Garraway IP The initiator element: a paradigm for core promoter heterogeneity within metazoan protein-coding genes. Cold Spr Harb Symp Quant Biol. 1998; 63: 21-31.
Brown KE, Guest SS, Smale ST, Hahm K, Merkenschlager M, Fisher AG Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin.Cell. 1997; 91: 845-854.
Emami KH, Jain A, Smale ST Mechanism of synergy between TATA and initiator: synergistic binding of TFIID following a putative TFIIA-induced isomerization. Genes & Dev. 1997; 11: 3007-3019.
Kaufmann J, Verrijzer CP, Shao J, Smale ST CIF, an essential cofactor for TFIID-dependent initiator function.Genes & Dev. 1996; 10: 873-886.
Ernst P, Smale ST Combinatorial regulation of transcription II: The immunoglobulin mu heavy chain gene. Immunity. 1995; 2: 427-438.
Ernst P, Smale ST Combinatorial regulation of transcription. I: General aspects of transcriptional control.Immunity. 1995; 2: 311-319.
Kaufmann J, Smale ST Direct recognition of initiator elements by a component of the transcription factor IID complex. Genes & Dev. 1994; 8: 821-829.