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Professor
and
Vice Chair,
Biological Chemistry
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Director,
Howard Hughes Undergraduate Research Program
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Associate Director,
JCCC Gene Regulation Program Area
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ACCESS Affinity Group:
ACCESS Affinity - Gene Regulation
Awards and Honors:
CaPCURE Research Awards, 1998-2000
JCCC David Paul Kane Scholar, 1998
ACCESS Curriculum Committee
ACCESS Steering Committee
Co-organizer, 2008 FASEB Summer Research Conference on Transcriptional Regulation During Cell Growth, Development and Differentiation.
Faculty Advisory Committee on the Minor in Biomedical Research
Faculty Oversight Committee for the Science Undergraduate Research Center
MBI Gene Regulation Program Steering Committee
MBI Graduate Committee
Medical Scientist Training Program Admissions Committee
Research Interest:
Turning genes on and off
Study of how genes are turned on and off using proteins and test tubes.
Biography:
Dr. Carey studies biochemical mechanisms of gene activation and silencing. In 1990, Dr. Carey established biochemical systems for studying gene regulation based on a model transcriptional activator termed GAL4-VP16. Using that system, Dr. Carey established a mechanism by which genes are controlled synergistically by upstream activators. Synergy is a key principle in gene regulation and underlies the combinatorial control of gene transcription. Throughout the 1990s, Dr. Carey’s lab showed that synergy is first manifested during assembly of transcription preinitiation complexes (PICs). His lab identified assembly of a co-activator complex, termed DAMed, as the key step influenced by activators. More recently, Dr. Carey has been studying the biochemistry of transcription on chromatin templates after a one year sabbatical at the Stowers Institute for Medical Research in 2006. Dr. Carey’s lab has shown how a protein termed p300 coordinates chromatin modification with assembly of the DAMed complex and then the PIC. His lab has also shown how a protein termed HP1 silences transcription by selectively affecting key components of the DAMed complex. His current work is focused on understanding the biochemical mechanisms underlying epigenetic control of gene expression.
Dr. Carey served as Director of the Jonsson Comprehensive Cancer Center Gene Regulation Program from 1999-2005 and is currently Associate Director. Dr. Carey co-founded the Cold Spring Harbor Eukaryotic Gene Expression Course with his UCLA colleague, Dr. Steven Smale, and served as course director in 1997. Drs. Carey and Smale wrote a 650-page textbook titled “Transcriptional Regulation in Eukaryotes; Concepts, Strategies and Techniques.” The first edition was published by CSHL Press in 2000 and the second edition was published in 2008. Dr. Carey is a scientific cofounder of Agensys, a biotechnology company focused on prostate cancer therapy. In 2000, during a leave of absence from UCLA, Dr. Carey served as Director of Biology at Genesoft, a company focused on cancer therapeutics targeting transcription factor binding sites in the genome. Dr. Carey is currently Chief Scientific Advisor for OncoTx, a biotech company focused on using transcription factors as therapeutic targets in melanoma and other cancers. Dr. Carey is on numerous committees at UCLA that oversee undergraduate and graduate research education.
Publications:
Smallwood Andrea, Black Joshua C, Tanese Naoko, Pradhan Sriharsa, Carey Michael HP1-mediated silencing targets Pol II coactivator complexes..
Nat. Struct. Mol. Biol..
2008; 15(3):
318-20.
Black Joshua C, Mosley Amber, Kitada Tasuku, Washburn Michael, Carey Michael The SIRT2 deacetylase regulates autoacetylation of p300..
Molecular cell.
2008; 32(3):
449-55.
Chin Hang Gyeong, Est����ve Pierre-Olivier, Pradhan Mihika, Benner Jack, Patnaik Debasis, Carey Michael F, Pradhan Sriharsa Automethylation of G9a and its implication in wider substrate specificity and HP1 binding..
Nucleic Acids Res..
2007; 35(21):
7313-23.
Li, B. Gogol, M. Carey, M. Lee, D. Seidel, C. Workman, J. L. Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin.
Science.
2007; 316( 5827):
1050-4.
Smallwood, A. Esteve, P. O. Pradhan, S. Carey, M. Functional cooperation between HP1 and DNMT1 mediates gene silencing.
Genes Dev.
2007; 21( 10):
1169-78.
Smallwood Andrea, Est����ve Pierre-Olivier, Pradhan Sriharsa, Carey Michael Functional cooperation between HP1 and DNMT1 mediates gene silencing..
Genes Dev..
2007; 21(10):
1169-78.
Li, B. Gogol, M. Carey, M. Pattenden, S. G. Seidel, C. Workman, J. L. Infrequently transcribed long genes depend on the Set2/Rpd3S pathway for accurate transcription.
Genes Dev.
2007; 21( 11):
1422-30.
Li, B. Carey, M. Workman, J. L. The role of chromatin during transcription.
Cell.
2007; 128( 4):
707-19.
Li Bing, Carey Michael, Workman Jerry L The role of chromatin during transcription..
Cell.
2007; 128(4):
707-19.
Black, J. C. Choi, J. E. Lombardo, S. R. Carey, M. A mechanism for coordinating chromatin modification and preinitiation complex assembly.
Mol Cell.
2006; 23( 6):
809-18.
Black Joshua C, Choi Janet E, Lombardo Sarah R, Carey Michael A mechanism for coordinating chromatin modification and preinitiation complex assembly..
Mol. Cell.
2006; 23(6):
809-18.
Kozeracki Carol A, Carey Michael F, Colicelli John, Levis-Fitzgerald Marc, Grossel Martha An intensive primary-literature-based teaching program directly benefits undergraduate science majors and facilitates their transition to doctoral programs..
Physiol. Genomics.
2006; 5(4):
340-7.
Esteve, P. O. Chin, H. G. Smallwood, A. Feehery, G. R. Gangisetty, O. Karpf, A. R. Carey, M. F. Pradhan, S. Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication.
Genes Dev.
2006; 20( 22):
3089-103.
Ilagan, R. Pottratz, J. Le, K. Zhang, L. Wong, S. G. Ayala, R. Iyer, M. Wu, L. Gambhir, S. S. Carey, M. Imaging mitogen-activated protein kinase function in xenograft models of prostate cancer.
Cancer Res.
2006; 66( 22):
10778-85.
Ilagan Romyla, Pottratz Jill, Le Kim, Zhang Liqun, Wong Steven G, Ayala Raul, Iyer Meera, Wu Lily, Gambhir Sanjiv S, Carey Michael Imaging mitogen-activated protein kinase function in xenograft models of prostate cancer..
Cancer Res..
2006; 66(22):
10778-85.
Wang Yanling, Iyer Meera, Annala Alexander, Wu Lily, Carey Michael, Gambhir Sanjiv S Noninvasive indirect imaging of vascular endothelial growth factor gene expression using bioluminescence imaging in living transgenic mice..
Physiol. Genomics.
2006; 24(2):
173-80.
Carey, M. Li, B. Workman, J. L. RSC exploits histone acetylation to abrogate the nucleosomal block to RNA polymerase II elongation.
Mol Cell.
2006; 24( 3):
481-7.
Carey Michael, Li Bing, Workman Jerry L RSC exploits histone acetylation to abrogate the nucleosomal block to RNA polymerase II elongation..
Mol. Cell.
2006; 24(3):
481-7.
Carey, M. Chromatin marks and machines, the missing nucleosome is a theme: gene regulation up and downstream.
Mol Cell.
2005; 17( 3):
323-30.
Sato Makoto, Johnson Mai, Zhang Liqun, Gambhir Sanjiv S, Carey Michael, Wu Lily Functionality of androgen receptor-based gene expression imaging in hormone refractory prostate cancer..
Clin. Cancer Res..
2005; 11(10):
3743-9.
Ilagan, R. Zhang, L. J. Pottratz, J. Le, K. Salas, S. Iyer, M. Wu, L. Gambhir, S. S. Carey, M. Imaging androgen receptor function during flutamide treatment in the LAPC9 xenograft model.
Mol Cancer Ther.
2005; 4( 11):
1662-9.
Ilagan Romyla, Zhang Liquin Joann, Pottratz Jill, Le Kim, Salas Sussan, Iyer Meera, Wu Lily, Gambhir Sanjiv S, Carey Michael Imaging androgen receptor function during flutamide treatment in the LAPC9 xenograft model..
Mol. Cancer Ther..
2005; 4(11):
1662-9.
Johnson Mai, Sato Makoto, Burton Jeremy, Gambhir Sanjiv S, Carey Michael, Wu Lily Micro-PET/CT monitoring of herpes thymidine kinase suicide gene therapy in a prostate cancer xenograft: the advantage of a cell-specific transcriptional targeting approach..
Metab. Clin. Exp..
2005; 4(4):
463-72.
Bourbon Henri-Marc, Aguilera Andres, Ansari Aseem Z, Asturias Francisco J, Berk Arnold J, Bjorklund Stefan, Blackwell T Keith, Borggrefe Tilman, Carey Michael, Carlson Marian, Conaway Joan W, Conaway Ronald C, Emmons Scott W, Fondell Joseph D, Freedman Leonard P, Fukasawa Toshio, Gustafsson Claes M, Han Min, He Xi, Herman Paul K, Hinnebusch Alan G, Holmberg Steen, Holstege Frank C, Jaehning Judith A, Kim Young-Joon, Kuras Laurent, Leutz Achim, Lis John T, Meisterernest Michael, Naar Anders M, Nasmyth Kim, Parvin Jeffrey D, Ptashne Mark, Reinberg Danny, Ronne Hans, Sadowski Ivan, Sakurai Hiroshi, Sipiczki Matthias, Sternberg Paul W, Stillman David J, Strich Randy, Struhl Kevin, Svejstrup Jasper Q, Tuck Simon, Winston Fred, Roeder Robert G, Kornberg Roger D A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II..
Mol. Cell.
2004; 14(5):
553-7.
Iyer Meera, Salazar Felix B, Lewis Xiaoman, Zhang Liqun, Carey Michael, Wu Lily, Gambhir Sanjiv S Noninvasive imaging of enhanced prostate-specific gene expression using a two-step transcriptional amplification-based lentivirus vector..
Mol. Ther..
2004; 10(3):
545-52.
Johnson, K. M. Wang, J. Smallwood, A. Carey, M. The immobilized template assay for measuring cooperativity in eukaryotic transcription complex assembly.
Methods Enzymol.
2004; 380:
207-19.
Johnson Kristina M, Wang Jin, Smallwood Andrea, Carey Michael The immobilized template assay for measuring cooperativity in eukaryotic transcription complex assembly..
Meth. Enzymol..
2004; 380(1):
207-19.
Johnson Kristina M, Carey Michael Assembly of a mediator/TFIID/TFIIA complex bypasses the need for an activator..
Curr. Biol..
2003; 13(9):
772-7.
Johnson, K. M. Carey, M. Assembly of a mediator/TFIID/TFIIA complex bypasses the need for an activator.
Curr Biol.
2003; 13( 9):
772-7.
Zhang Liqun, Johnson Mai, Le Kim H, Sato Makoto, Ilagan Romyla, Iyer Meera, Gambhir Sanjiv S, Wu Lily, Carey Michael Interrogating androgen receptor function in recurrent prostate cancer..
Cancer Res..
2003; 63(15):
4552-60.
Zhang, L. Johnson, M. Le, K. H. Sato, M. Ilagan, R. Iyer, M. Gambhir, S. S. Wu, L. Carey, M. Interrogating androgen receptor function in recurrent prostate cancer.
Cancer Res.
2003; 63( 15):
4552-60.
Zhang, L. Adams, J. Y. Billick, E. Ilagan, R. Iyer, M. Le, K. Smallwood, A. Gambhir, S. S. Carey, M. Wu, L. Molecular engineering of a two-step transcription amplification (TSTA) system for transgene delivery in prostate cancer.
Mol Ther.
2002; 5( 3):
223-32.
Johnson, K. M. Wang, J. Smallwood, A. Arayata, C. Carey, M. TFIID and human mediator coactivator complexes assemble cooperatively on promoter DNA.
Genes Dev.
2002; 16( 14):
1852-63.
Wu, L. Matherly, J. Smallwood, A. Adams, J. Y. Billick, E. Belldegrun, A. Carey, M. Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors.
Gene Ther.
2001; 8( 18):
1416-26.
Johnson, K. M. Mitsouras, K. Carey, M. Eukaryotic transcription: the core of eukaryotic gene activation.
Curr Biol.
2001; 11( 13):
R510-3.
Wang, J. Ellwood, K. Lehman, A. Carey, M. F. She, Z. S. A mathematical model for synergistic eukaryotic gene activation.
J Mol Biol.
1999; 286( 2):
315-25.
Ellwood, K. Huang, W. Johnson, R. Carey, M. Multiple layers of cooperativity regulate enhanceosome-responsive RNA polymerase II transcription complex assembly.
Mol Cell Biol.
1999; 19( 4):
2613-23.
Lehman, A. M. Ellwood, K. B. Middleton, B. E. Carey, M. Compensatory energetic relationships between upstream activators and the RNA polymerase II general transcription machinery.
J Biol Chem.
1998; 273( 2):
932-9.
Ellwood, K. Chi, T. Huang, W. Mitsouras, K. Carey, M. Cooperative assembly of RNA polymerase II transcription complexes.
Cold Spring Harb Symp Quant Biol.
1998; 63:
253-61.
Carey, M. The enhanceosome and transcriptional synergy.
Cell.
1998; 92( 1):
5-8.
Hori, R. Carey, M. Transcription: TRF walks the walk but can it talk the talk?.
Curr Biol.
1998; 8( 4):
R124-7.
Hori, R. Carey, M. Protease footprinting analysis of ternary complex formation by human TFIIA.
J Biol Chem.
1997; 272( 2):
1180-7.
Tantin, D. Kansal, A. Carey, M. Recruitment of the putative transcription-repair coupling factor CSB/ERCC6 to RNA polymerase II elongation complexes.
Mol Cell Biol.
1997; 17( 12):
6803-14.
Chi, T. Carey, M. Assembly of the isomerized TFIIA--TFIID--TATA ternary complex is necessary and sufficient for gene activation.
Genes Dev.
1996; 10( 20):
2540-50.
Tantin, D. Chi, T. Hori, R. Pyo, S. Carey, M. Biochemical mechanism of transcriptional activation by GAL4-VP16.
Methods Enzymol.
1996; 274:
133-49.
Chi, T. Lieberman, P. Ellwood, K. Carey, M. A general mechanism for transcriptional synergy by eukaryotic activators.
Nature.
1995; 377( 6546):
254-7.
Hori, R. Pyo, S. Carey, M. Protease footprinting reveals a surface on transcription factor TFIIB that serves as an interface for activators and coactivators.
Proc Natl Acad Sci U S A.
1995; 92( 13):
6047-51.
Carey, M. F. Transcriptional activation. A holistic view of the complex.
Curr Biol.
1995; 5( 9):
1003-5.
Tantin, D. Carey, M. A heteroduplex template circumvents the energetic requirement for ATP during activated transcription by RNA polymerase II.
J Biol Chem.
1994; 269( 26):
17397-400.
Ohashi, Y. Brickman, J. M. Furman, E. Middleton, B. Carey, M. Modulating the potency of an activator in a yeast in vitro transcription system.
Mol Cell Biol.
1994; 14( 4):
2731-9.
Hori, R. Carey, M. The role of activators in assembly of RNA polymerase II transcription complexes.
Curr Opin Genet Dev.
1994; 4( 2):
236-44.
Carey, M. Transcription. Simplifying the complex.
Nature.
1994; 368( 6470):
402-3.
Chi, T. Carey, M. The ZEBRA activation domain: modular organization and mechanism of action.
Mol Cell Biol.
1993; 13( 11):
7045-55.
Emami, K. H. Carey, M. A synergistic increase in potency of a multimerized VP16 transcriptional activation domain.
Embo J.
1992; 11( 13):
5005-12.
Marmorstein, R. Carey, M. Ptashne, M. Harrison, S. C. DNA recognition by GAL4: structure of a protein-DNA complex.
Nature.
1992; 356( 6368):
408-14.
Wang, W. Carey, M. Gralla, J. D. Polymerase II promoter activation: closed complex formation and ATP-driven start site opening.
Science.
1992; 255( 5043):
450-3.
Wang, W. Gralla, J. D. Carey, M. The acidic activator GAL4-AH can stimulate polymerase II transcription by promoting assembly of a closed complex requiring TFIID and TFIIA.
Genes Dev.
1992; 6( 9):
1716-27.
Carey, M. Kolman, J. Katz, D. A. Gradoville, L. Barberis, L. Miller, G. Transcriptional synergy by the Epstein-Barr virus transactivator ZEBRA.
J Virol.
1992; 66( 8):
4803-13.
Carey, M. Mechanistic advances in eukaryotic gene activation.
Curr Opin Cell Biol.
1991; 3( 3):
452-60.
Carey, M. Lin, Y. S. Green, M. R. Ptashne, M. A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives.
Nature.
1990; 345( 6273):
361-4.
Carey, M. Leatherwood, J. Ptashne, M. A potent GAL4 derivative activates transcription at a distance in vitro.
Science.
1990; 247( 4943):
710-2.
Lin, Y. S. Carey, M. Ptashne, M. Green, M. R. How different eukaryotic transcriptional activators can cooperate promiscuously.
Nature.
1990; 345( 6273):
359-61.
Chasman, D. I. Leatherwood, J. Carey, M. Ptashne, M. Kornberg, R. D. Activation of yeast polymerase II transcription by herpesvirus VP16 and GAL4 derivatives in vitro.
Mol Cell Biol.
1989; 9( 11):
4746-9.
Carey, M. Kakidani, H. Leatherwood, J. Mostashari, F. Ptashne, M. An amino-terminal fragment of GAL4 binds DNA as a dimer.
J Mol Biol.
1989; 209( 3):
423-32.
Schreck, R. Carey, M. F. Grummt, I. Transcriptional enhancement by upstream activators is brought about by different molecular mechanisms for class I and II RNA polymerase genes.
Embo J.
1989; 8( 10):
3011-7.
Carey, M. F. Singh, K. Enhanced B2 transcription in simian virus 40-transformed cells is mediated through the formation of RNA polymerase III transcription complexes on previously inactive genes.
Proc Natl Acad Sci U S A.
1988; 85( 19):
7059-63.
Lin, Y. S. Carey, M. F. Ptashne, M. Green, M. R. GAL4 derivatives function alone and synergistically with mammalian activators in vitro.
Cell.
1988; 54( 5):
659-64.
Horikoshi, M. Carey, M. F. Kakidani, H. Roeder, R. G. Mechanism of action of a yeast activator: direct effect of GAL4 derivatives on mammalian TFIID-promoter interactions.
Cell.
1988; 54( 5):
665-9.
Carey, M. F. Gerrard, S. P. Cozzarelli, N. R. Analysis of RNA polymerase III transcription complexes by gel filtration.
J Biol Chem.
1986; 261( 9):
4309-17.
Carey, M. F. Singh, K. Botchan, M. Cozzarelli, N. R. Induction of specific transcription by RNA polymerase III in transformed cells.
Mol Cell Biol.
1986; 6( 9):
3068-76.
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