Stephen Smale

Professor, MIMG, University of California Los Angeles

Professor, Medicine, University of California Los Angeles

UC Profile
UCLA Jonsson Comprehensive Cancer Center
UCLA DGSOM
UCLA Department of Microbiology, Immunology, & Molecular Genetics

Stephen T. Smale is a molecular immunologist and molecular biologist who arrived at UCLA in 1990 as an Assistant Professor. 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 at UCLA, 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). From 2015-2021, he served as Vice Dean for Research in the David Geffen School of Medicine. He currently serves as Senior Scientific Officer for the Howard Hughes Medical Institute, as well as a member of the editorial advisory boards for the journals Immunity, Genes & Development, and Trends in Immunology. The research in Dr. Smale's lab is diverse and spans the areas of gene regulation, inflammation, molecular immunology, stem cell biology, and leukemogenesis. A major interest is the molecular mechanisms of pro-inflammatory gene regulation, with an emphasize on the genomic logic through which signaling pathways, transcription factors, and chromatin structure orchestrate selective inflammatory and innate immune responses to a broad range of microbial and environmental threats.

Interests

leukemogenesis, pro-inflammatory gene regulation, molecular immunology, stem cell biology

Education and Training

University of California, BerkeleyPh.D.1986Biochemistry
Cornell UniversityA.B.1981Chemistry

Awards and Honors

  • Life Sciences Excellence Award in Educational Innovation, UCLA Division of Life Sciences, College of Letters and Science, 2016.
  • Postdoctoral Fellow, Helen Hay Whitney Foundation, 1986-1989.
  • Keynote Speaker, European Macrophage and Dendritic Cell Society Annual Meeting, Debrecan, Hungary, 2010.
  • Sherie L. and Donald G. Morrison Chair in Molecular Immunology, UCLA, 2014-pres.
  • Fellow, American Association for the Advancement of Science, 2020.
  • Investigator, Howard Hughes Medical Institute, 1990-2007.
  • Graduate Research Fellowship, National Science Foundation, 1982-1986.
  • Keynote Speaker, Instituto di Ricerca in Biomedicina Alumni Symposium, Bellinzona, Switzerland, 2014.
  • Keynote Speaker, Keystone Symposium, “Transcription and RNA Regulation in Inflammation and Immunity,” Tahoe City, CA, 2019.

Publications

  1. Bideyan L, López Rodríguez M, Priest C, Kennelly JP, Gao Y, Ferrari A, Rajbhandari P, Feng AC, Tevosian SG, Smale ST, Tontonoz P. Hepatic GATA4 regulates cholesterol and triglyceride homeostasis in collaboration with LXRs.. Genes & development, 2022.
  2. Lo JH, Edwards M, Langerman J, Sridharan R, Plath K, Smale ST. Oct4:Sox2 binding is essential for establishing but not maintaining active and silent states of dynamically regulated genes in pluripotent cells.. Genes & development, 2022.
  3. Smale ST. Allogeneic hematopoietic stem cell transplantation: lessons learned by a molecular immunologist/transplant patient.. Trends in immunology, 2022.
  4. Langerman J, Lopez D, Pellegrini M, Smale ST. Species-Specific Relationships between DNA and Chromatin Properties of CpG Islands in Embryonic Stem Cells and Differentiated Cells.. Stem cell reports, 2021.
  5. Zhou QD, Chi X, Lee MS, Hsieh WY, Mkrtchyan JJ, Feng AC, He C, York AG, Bui VL, Kronenberger EB, Ferrari A, Xiao X, Daly AE, Tarling EJ, Damoiseaux R, Scumpia PO, Smale ST, Williams KJ, Tontonoz P, Bensinger SJ. Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins.. Nature immunology, 2020.
  6. Hsieh WY, Zhou QD, York AG, Williams KJ, Scumpia PO, Kronenberger EB, Hoi XP, Su B, Chi X, Bui VL, Khialeeva E, Kaplan A, Son YM, Divakaruni AS, Sun J, Smale ST, Flavell RA, Bensinger SJ. Toll-Like Receptors Induce Signal-Specific Reprogramming of the Macrophage Lipidome.. Cell metabolism, 2020.
  7. Weinmann AS, Youngblood BA, Smale ST, Brink R, Schatz DG, McHeyzer-Williams M. A Future Outlook on Molecular Mechanisms of Immunity.. Trends in immunology, 2020.
  8. Rajbhandari P, Arneson D, Hart SK, Ahn IS, Diamante G, Santos LC, Zaghari N, Feng AC, Thomas BJ, Vergnes L, Lee SD, Rajbhandari AK, Reue K, Smale ST, Yang X, Tontonoz P. Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes.. eLife, 2019.
  9. Comoglio F, Simonatto M, Polletti S, Liu X, Smale ST, Barozzi I, Natoli G. Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells.. Genes & development, 2019.
  10. Fu K, Chronis C, Soufi A, Bonora G, Edwards M, Smale ST, Zaret KS, Plath K, Pellegrini M. Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming.. BMC genomics, 2018.
  11. Sallam T, Jones M, Thomas BJ, Wu X, Gilliland T, Qian K, Eskin A, Casero D, Zhang Z, Sandhu J, Salisbury D, Rajbhandari P, Civelek M, Hong C, Ito A, Liu X, Daniel B, Lusis AJ, Whitelegge J, Nagy L, Castrillo A, Smale S, Tontonoz P. Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA.. Nature medicine, 2018.
  12. Rajbhandari P, Thomas BJ, Feng AC, Hong C, Wang J, Vergnes L, Sallam T, Wang B, Sandhu J, Seldin MM, Lusis AJ, Fong LG, Katz M, Lee R, Young SG, Reue K, Smale ST, Tontonoz P. IL-10 Signaling Remodels Adipose Chromatin Architecture to Limit Thermogenesis and Energy Expenditure.. Cell, 2017.
  13. Purbey PK, Scumpia PO, Kim PJ, Tong AJ, Iwamoto KS, McBride WH, Smale ST. Defined Sensing Mechanisms and Signaling Pathways Contribute to the Global Inflammatory Gene Expression Output Elicited by Ionizing Radiation.. Immunity, 2017.
  14. Madigan CA, Cambier CJ, Kelly-Scumpia KM, Scumpia PO, Cheng TY, Zailaa J, Bloom BR, Moody DB, Smale ST, Sagasti A, Modlin RL, Ramakrishnan L. A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy.. Cell, 2017.
  15. Scumpia PO, Botten GA, Norman JS, Kelly-Scumpia KM, Spreafico R, Ruccia AR, Purbey PK, Thomas BJ, Modlin RL, Smale ST. Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense.. PLoS pathogens, 2017.
  16. Schjerven H, Ayongaba EF, Aghajanirefah A, McLaughlin J, Cheng D, Geng H, Boyd JR, Eggesbø LM, Lindeman I, Heath JL, Park E, Witte ON, Smale ST, Frietze S, Müschen M. Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre-B ALL.. The Journal of experimental medicine, 2017.
  17. Thomas BJ, Smale ST. The Ly6C(lo)-Down: Targeting Developmental Enhancers for Cell Subset Depletion.. Immunity, 2016.
  18. 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.
  19. Cunningham CR, Champhekar A, Tullius MV, Dillon BJ, Zhen A, de la Fuente JR, Herskovitz J, Elsaesser H, Snell LM, Wilson EB, de la Torre JC, Kitchen SG, Horwitz MA, Bensinger SJ, Smale ST, Brooks DG. Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence.. PLoS pathogens, 2016.
  20. Arenzana TL, Schjerven H, Smale ST. Regulation of gene expression dynamics during developmental transitions by the Ikaros transcription factor.. Genes & development, 2015.
  21. Lissner MM, 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.
  22. Smale ST, Natoli G. Transcriptional control of inflammatory responses.. Cold Spring Harbor perspectives in biology, 2014.
  23. Heller JJ, Schjerven H, Li S, Lee A, Qiu J, Chen ZM, Smale ST, Zhou L. Restriction of IL-22-producing T cell responses and differential regulation of regulatory T cell compartments by zinc finger transcription factor Ikaros.. Journal of immunology (Baltimore, Md. : 1950), 2014.
  24. 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 Harbor symposia on quantitative biology, 2014.
  25. Smale ST. Transcriptional regulation in the immune system: a status report.. Trends in immunology, 2014.
  26. Garcia AJ, Ruscetti M, Arenzana TL, Tran LM, Bianci-Frias D, Sybert E, Priceman SJ, Wu L, Nelson PS, Smale ST, Wu H. Pten null prostate epithelium promotes localized myeloid-derived suppressor cell expansion and immune suppression during tumor initiation and progression.. Molecular and cellular biology, 2014.
  27. Smale ST, Tarakhovsky A, Natoli G. Chromatin contributions to the regulation of innate immunity.. Annual review of immunology, 2014.
  28. 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 immunology, 2013.
  29. Pandya-Jones A, Bhatt DM, Lin CH, Tong AJ, Smale ST, Black DL. Splicing kinetics and transcript release from the chromatin compartment limit the rate of Lipid A-induced gene expression.. RNA (New York, N.Y.), 2013.
  30. Ferreirós-Vidal I, Carroll T, Taylor B, Terry A, Liang Z, Bruno L, Dharmalingam G, Khadayate S, Cobb BS, Smale ST, Spivakov M, Srivastava P, Petretto E, Fisher AG, Merkenschlager M. Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.. Blood, 2013.
  31. Xu J, Smale ST. Designing an enhancer landscape.. Cell, 2012.
  32. Murray PJ, Smale ST. Restraint of inflammatory signaling by interdependent strata of negative regulatory pathways.. Nature immunology, 2012.
  33. Bhatt DM, Pandya-Jones A, Tong AJ, Barozzi I, Lissner MM, Natoli G, Black DL, Smale ST. Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions.. Cell, 2012.
  34. 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 immunology, 2012.
  35. Smale ST. Dimer-specific regulatory mechanisms within the NF-κB family of transcription factors.. Immunological reviews, 2012.
  36. Smale ST. Transcriptional regulation in the innate immune system.. Current opinion in immunology, 2012.
  37. 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-κB family DNA binding.. Nature immunology, 2011.
  38. Smale ST. Hierarchies of NF-κB target-gene regulation.. Nature immunology, 2011.
  39. Smith AM, Qualls JE, O'Brien K, Balouzian L, Johnson PF, Schultz-Cherry S, Smale ST, Murray PJ. A distal enhancer in Il12b is the target of transcriptional repression by the STAT3 pathway and requires the basic leucine zipper (B-ZIP) protein NFIL3.. The Journal of biological chemistry, 2011.
  40. Kobayashi T, Matsuoka K, Sheikh SZ, Elloumi HZ, Kamada N, Hisamatsu T, Hansen JJ, Doty KR, Pope SD, Smale ST, Hibi T, Rothman PB, Kashiwada M, Plevy SE. NFIL3 is a regulator of IL-12 p40 in macrophages and mucosal immunity.. Journal of immunology (Baltimore, Md. : 1950), 2011.
  41. Mukhopadhyay S, Plüddemann A, Hoe JC, Williams KJ, Varin A, Makepeace K, Aknin ML, Bowdish DM, Smale ST, Barclay AN, Gordon S. Immune inhibitory ligand CD200 induction by TLRs and NLRs limits macrophage activation to protect the host from meningococcal septicemia.. Cell host & microbe, 2010.
  42. Smale ST. Pioneer factors in embryonic stem cells and differentiation.. Current opinion in genetics & development, 2010.
  43. Smale ST. Seq-ing LPS-induced enhancers.. Immunity, 2010.
  44. Smale ST. Selective transcription in response to an inflammatory stimulus.. Cell, 2010.
  45. 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 & development, 2009.
  46. Papathanasiou P, Attema JL, Karsunky H, Hosen N, Sontani Y, Hoyne GF, Tunningley R, Smale ST, Weissman IL. Self-renewal of the long-term reconstituting subset of hematopoietic stem cells is regulated by Ikaros.. Stem cells (Dayton, Ohio), 2009.
  47. Sen R, Smale ST. Selectivity of the NF-{kappa}B response.. Cold Spring Harbor perspectives in biology, 2009.
  48. Papathanasiou P, Attema JL, Karsunky H, Xu J, Smale ST, Weissman IL. Evaluation of the long-term reconstituting subset of hematopoietic stem cells with CD150.. Stem cells (Dayton, Ohio), 2009.
  49. 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.
  50. Reynaud D, Demarco IA, Reddy KL, Schjerven H, Bertolino E, Chen Z, Smale ST, Winandy S, Singh H. Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros.. Nature immunology, 2008.
  51. Kayama H, Ramirez-Carrozzi VR, Yamamoto M, Mizutani T, Kuwata H, Iba H, Matsumoto M, Honda K, Smale ST, Takeda K. Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IkappaBzeta.. The Journal of biological chemistry, 2008.
  52. Sridharan R, Smale ST. Predominant interaction of both Ikaros and Helios with the NuRD complex in immature thymocytes.. The Journal of biological chemistry, 2007.
  53. Attema JL, Papathanasiou P, Forsberg EC, Xu J, Smale ST, Weissman IL. Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis.. Proceedings of the National Academy of Sciences of the United States of America, 2007.
  54. Xu J, Pope SD, Jazirehi AR, Attema JL, Papathanasiou P, Watts JA, Zaret KS, Weissman IL, Smale ST. Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells.. Proceedings of the National Academy of Sciences of the United States of America, 2007.
  55. Thompson EC, Cobb BS, Sabbattini P, Meixlsperger S, Parelho V, Liberg D, Taylor B, Dillon N, Georgopoulos K, Jumaa H, Smale ST, Fisher AG, Merkenschlager M. Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits.. Immunity, 2007.
  56. Zhou L, Nazarian AA, Xu J, Tantin D, Corcoran LM, Smale ST. An inducible enhancer required for Il12b promoter activity in an insulated chromatin environment.. Molecular and cellular biology, 2007.
  57. Cobb BS, Hertweck A, Smith J, O'Connor E, Graf D, Cook T, Smale ST, Sakaguchi S, Livesey FJ, Fisher AG, Merkenschlager M. A role for Dicer in immune regulation.. The Journal of experimental medicine, 2006.
  58. Li CC, Ramirez-Carrozzi VR, Smale ST. Pursuing gene regulation 'logic' via RNA interference and chromatin immunoprecipitation.. Nature immunology, 2006.
  59. Smale ST, Dorshkind K. Hematopoiesis flies high with Ikaros.. Nature immunology, 2006.
  60. Ramirez-Carrozzi VR, Nazarian AA, Li CC, Gore SL, Sridharan R, Imbalzano AN, Smale ST. Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response.. Genes & development, 2006.
  61. 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 & development, 2005.
  62. Dovat S, Montecino-Rodriguez E, Schuman V, Teitell MA, Dorshkind K, Smale ST. Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis.. Journal of immunology (Baltimore, Md. : 1950), 2005.
  63. Cobb BS, Nesterova TB, Thompson E, Hertweck A, O'Connor E, Godwin J, Wilson CB, Brockdorff N, Fisher AG, Smale ST, Merkenschlager M. T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer.. The Journal of experimental medicine, 2005.
  64. Su RC, Sridharan R, Smale ST. Assembly of silent chromatin during thymocyte development.. Seminars in immunology, 2005.
  65. Su RC, Brown KE, Saaber S, Fisher AG, Merkenschlager M, Smale ST. Dynamic assembly of silent chromatin during thymocyte maturation.. Nature genetics, 2004.
  66. Zhou L, Nazarian AA, Smale ST. Interleukin-10 inhibits interleukin-12 p40 gene transcription by targeting a late event in the activation pathway.. Molecular and cellular biology, 2004.
  67. Cupit PM, Hansen JD, McCarty AS, White G, Chioda M, Spada F, Smale ST, Cunningham C. Ikaros family members from the agnathan Myxine glutinosa and the urochordate Oikopleura dioica: emergence of an essential transcription factor for adaptive immunity.. Journal of immunology (Baltimore, Md. : 1950), 2003.
  68. Liberg D, Smale ST, Merkenschlager M. Upstream of Ikaros.. Trends in immunology, 2003.
  69. Smale ST. A Th2 cytokine LCR. Adding a new piece to the regulatory puzzle.. Immunity, 2003.
  70. Bradley MN, Zhou L, Smale ST. C/EBPbeta regulation in lipopolysaccharide-stimulated macrophages.. Molecular and cellular biology, 2003.
  71. Smale ST. The establishment and maintenance of lymphocyte identity through gene silencing.. Nature immunology, 2003.
  72. 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.
  73. Ronni T, Agarwal V, Haykinson M, Haberland ME, Cheng G, Smale ST. Common interaction surfaces of the toll-like receptor 4 cytoplasmic domain stimulate multiple nuclear targets.. Molecular and cellular biology, 2003.
  74. Smale ST, Kadonaga JT. The RNA polymerase II core promoter.. Annual review of biochemistry, 2003.
  75. McCarty AS, Kleiger G, Eisenberg D, Smale ST. Selective dimerization of a C2H2 zinc finger subfamily.. Molecular cell, 2003.
  76. 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 & development, 2002.
  77. Smale ST, Fisher AG. Chromatin structure and gene regulation in the immune system.. Annual review of immunology, 2001.