Michael R Stallcup, PhD
Michael R Stallcup, PhD
Professor of Biochemistry & Molecular Medicine
NOR 6316 1441 Eastlake Avenue Health Sciences Campus Los Angeles
Michael R. Stallcup, Ph.D. received his B.A. at Yale University, his Ph.D. at the University of California at Berkeley, and did his postdoctoral training at the University of California at San Francisco. He began his career on the faculty at the University of South Carolina, joining USC in 1985 where he is a Professor in the Department of Biochemistry and Molecular Biology. He serves as co-leader with Dr. Peggy Farnham of the Epigenetics and Regulation Program. In his studies on transcriptional regulation by steroid hormone receptions, he is one of the leading researchers in discovering and characterizing transcriptional coregulators. Specifically his research focuses on coregulators that help steroid receptors alter chromatin structure and recruit RNA polymerase to the target genes that are regulated by steroid hormones and their receptors. His lab discovered the first histone methyltransferase and was the first to demonstrate a role for histone methylation in transcriptional regulation. His lab is currently exploring the molecular mechanisms of coregulator action and the physiological roles of specific coregulators in cancer and inflammatory diseases.

Current projects are examining the role of the homologous coregulators G9a (EHMT2) and GLP (EHMT1), which methylate histones and other proteins, in glucocorticoid-regulated transcription. His lab discovered that G9a and GLP can serve as coactivators for some genes and corepressors for other genes. They showed that the coactivator activity is controlled by adjacent methylation and phosphorylation modifications: self-methylation is required for coactivator activity, while phosphorylation by Aurora kinase B inhibits coactivator activity. His lab showed that G9a and GLP are required for glucocorticoid-induced expression of specific genes that lead to cell death in leukemia cells. Glucocorticoids are used as a standard part of therapy for leukemia and other hematologic malignancies, but many patients become resistant to this therapy. Based on the above molecular mechanism, Dr. Stallcup's lab has shown that Aurora kinase B inhibitors and demethylase inhibitors can enhance the coactivator activity of G9a, enhance glucocorticoid activation of the genes that promote cell death, and enhance glucocorticoid-induced cell death in leukemia cells, including cells from leukemia patients that are resistant to the standard therapy. Studies in mouse models are currently underway with an aim to generate preclinical data to support clinical trials conducted by clinical collaborators.

In other projects, Dr. Stallcup's lab is also exploring the roles of G9a and GLP and their post-translational modification in other physiological systems, including energy metabolism in liver, fat, and muscle tissues.

Research Interests: Regulation of transcription by steroid hormones; molecular and physiological roles of transcriptional coregulators

Disease Models: cancer, inflammatory diseases

National Institutes of Health: Chair, Molecular and Cellular Endocrinology Study Section, 2014-2016

University of Southern California: USC Mellon Award for Excellence in Faculty Mentoring, 2010

American Association for the Advancement of Science: Fellow, 2009

National Institutes of Health, NIDDK: MERIT Award, 2008-2017

Dept of Pathology, University of Southern California: Distinguished Service Award, 2006

Journal of Biological Chemistry: Editorial Board, 2004-2009

Keck School of Medicine, University of Southern California: Outstanding Gaduate Student Teaching Award, 2001

Molecular Endocrinology: Editorial Board, 1999-2002

American Cancer Society: Chair, Tumor Biochemistry and Endocrinology Study Section, 1997-1998

Molecular Endocrinology: Editorial Board, 1990-1994

Dept of Pathology, University of Southern California: R.S. Cleland Teaching Award (6 times), 1988-2003

National Institutes of Health: Research Career Development Award, 1983-1988

National Institutes of Health: National Research Service Award, 1977-1979

American Cancer Society: Postdoctoral Fellowship, 1974-1975

National Science Foundation: Graduate Traineeship, 1969-1972

Yale University: Graduated Magna Cum Laude, 1969

Yale University: Phi Beta Kappa, 1967

Relapse-associated AURKB blunts the glucocorticoid sensitivity of B cell acute lymphoblastic leukemia Proc Natl Acad Sci U S A. 2019 Feb 07. . View in PubMed

Aberrant expression of SETD1A promotes survival and migration of estrogen receptor a-positive breast cancer cells Int J Cancer. 2018 Dec 01; 143(11):2871-2883. . View in PubMed

Increasing G9a automethylation sensitizes B acute lymphoblastic leukemia cells to glucocorticoid-induced death Cell Death Dis. 2018 Oct 10; 9(10):1038. . View in PubMed

Aberrant expression of SETD1A promotes survival and migration of estrogen receptor a-positive breast cancer cells Int J Cancer. 2018 Sep 07. . View in PubMed

Different chromatin and DNA sequence characteristics define glucocorticoid receptor binding sites that are blocked or not blocked by coregulator Hic-5 PLoS One. 2018; 13(5):e0196965. . View in PubMed

A post-translational modification switch controls coactivator function of histone methyltransferases G9a and GLP EMBO Rep. 2017 08; 18(8):1442-1459. . View in PubMed

Glucocorticoid receptor binding to chromatin is selectively controlled by the coregulator Hic-5 and chromatin remodeling enzymes J Biol Chem. 2017 06 02; 292(22):9320-9334. . View in PubMed

Selective coregulator function and restriction of steroid receptor chromatin occupancy by Hic-5 Mol Endocrinol. 2015 May; 29(5):716-29. . View in PubMed

Identifying differential transcription factor binding in ChIP-seq Front Genet. 2015; 6:169. . View in PubMed

Glucocorticoid receptor binds half sites as a monomer and regulates specific target genes Genome Biol. 2014 Jul 31; 15(7):418. . View in PubMed

Coregulator cell cycle and apoptosis regulator 1 (CCAR1) positively regulates adipocyte differentiation through the glucocorticoid signaling pathway J Biol Chem. 2014 Jun 13; 289(24):17078-86. . View in PubMed

Hic-5 is a transcription coregulator that acts before and/or after glucocorticoid receptor genome occupancy in a gene-selective manner Proc Natl Acad Sci U S A. 2014 Mar 18; 111(11):4007-12. . View in PubMed

Establishment of active chromatin structure at enhancer elements by mixed-lineage leukemia 1 to initiate estrogen-dependent gene expression Nucleic Acids Res. 2014 Feb; 42(4):2245-56. . View in PubMed

Role of distinct surfaces of the G9a ankyrin repeat domain in histone and DNA methylation during embryonic stem cell self-renewal and differentiation Epigenetics Chromatin. 2014; 7:27. . View in PubMed

Distinct, genome-wide, gene-specific selectivity patterns of four glucocorticoid receptor coregulators Nucl Recept Signal. 2014; 12:e002. . View in PubMed

Aberrant BAF57 signaling facilitates prometastatic phenotypes Clin Cancer Res. 2013 May 15; 19(10):2657-67. . View in PubMed

cAMP response element-binding protein interacts with and stimulates the proteasomal degradation of the nuclear receptor coactivator GRIP1 Endocrinology. 2013 Apr; 154(4):1513-27. . View in PubMed

G9a functions as a molecular scaffold for assembly of transcriptional coactivators on a subset of glucocorticoid receptor target genes Proc Natl Acad Sci U S A. 2012 Nov 27; 109(48):19673-8. . View in PubMed

Recruitment of coregulator G9a by Runx2 for selective enhancement or suppression of transcription J Cell Biochem. 2012 Jul; 113(7):2406-14. . View in PubMed

Gene-specific patterns of coregulator requirements by estrogen receptor-a in breast cancer cells Mol Endocrinol. 2012 Jun; 26(6):955-66. . View in PubMed

Selective roles for cAMP response element-binding protein binding protein and p300 protein as coregulators for androgen-regulated gene expression in advanced prostate cancer cells J Biol Chem. 2012 Feb 03; 287(6):4000-13. . View in PubMed

Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cells Epigenetics Chromatin. 2012 Jan 27; 5(1):3. . View in PubMed

A distinct mechanism for coactivator versus corepressor function by histone methyltransferase G9a in transcriptional regulation J Biol Chem. 2011 Dec 09; 286(49):41963-71. . View in PubMed

Recognition of enhancer element-specific histone methylation by TIP60 in transcriptional activation Nat Struct Mol Biol. 2011 Nov 13; 18(12):1358-65. . View in PubMed

Reciprocal roles of DBC1 and SIRT1 in regulating estrogen receptor a activity and co-activator synergy Nucleic Acids Res. 2011 Sep 01; 39(16):6932-43. . View in PubMed

Roles of protein arginine methylation in DNA damage signaling pathways is CARM1 a life-or-death decision point? Cell Cycle. 2011 May 01; 10(9):1343-4.. View in PubMed

A coactivator role of CARM1 in the dysregulation of ß-catenin activity in colorectal cancer cell growth and gene expression Mol Cancer Res. 2011 May; 9(5):660-70. . View in PubMed

Regulated recruitment of tumor suppressor BRCA1 to the p21 gene by coactivator methylation Genes Dev. 2011 Jan 15; 25(2):176-88. . View in PubMed

A chloroacetamidine-based inactivator of protein arginine methyltransferase 1: design, synthesis, and in vitro and in vivo evaluation Chembiochem. 2010 Jun 14; 11(9):1219-23. . View in PubMed

Recruitment of the SWI/SNF chromatin remodeling complex to steroid hormone-regulated promoters by nuclear receptor coactivator flightless-I J Biol Chem. 2009 Oct 23; 284(43):29298-309. . View in PubMed

Requirement of cell cycle and apoptosis regulator 1 for target gene activation by Wnt and beta-catenin and for anchorage-independent growth of human colon carcinoma cells J Biol Chem. 2009 Jul 31; 284(31):20629-37. . View in PubMed

Minireview: protein arginine methylation of nonhistone proteins in transcriptional regulation Mol Endocrinol. 2009 Apr; 23(4):425-33. . View in PubMed

Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort BMC Cancer. 2009 Jan 30; 9:43. . View in PubMed

Modulation of Runx2 activity by estrogen receptor-alpha: implications for osteoporosis and breast cancer Endocrinology. 2008 Dec; 149(12):5984-95. . View in PubMed

CCAR1, a key regulator of mediator complex recruitment to nuclear receptor transcription complexes Mol Cell. 2008 Aug 22; 31(4):510-9. . View in PubMed

Inhibition of cyclin D1 gene transcription by Brg-1 Cell Cycle. 2008 Mar 01; 7(5):647-55. . View in PubMed

The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules Nat Struct Mol Biol. 2008 Mar; 15(3):245-50. . View in PubMed

Differential regulation of the two transcriptional activation domains of the coiled-coil coactivator CoCoA by sumoylation BMC Mol Biol. 2008 Jan 25; 9:12. . View in PubMed

Surface-scanning mutational analysis of protein arginine methyltransferase 1: roles of specific amino acids in methyltransferase substrate specificity, oligomerization, and coactivator function Mol Endocrinol. 2007 Jun; 21(6):1381-93. . View in PubMed

Role of GAC63 in transcriptional activation mediated by beta-catenin Nucleic Acids Res. 2007; 35(6):2084-92. . View in PubMed

Role of the N-terminal activation domain of the coiled-coil coactivator in mediating transcriptional activation by beta-catenin Mol Endocrinol. 2006 Dec; 20(12):3251-62. . View in PubMed

Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization Biochemistry. 2006 Oct 03; 45(39):11727-36. . View in PubMed

Transcriptional intermediary factor 1alpha mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor-interacting protein 1 nuclear receptor coactivators Mol Endocrinol. 2006 Jun; 20(6):1276-86. . View in PubMed

Role of GAC63 in transcriptional activation mediated by the aryl hydrocarbon receptor J Biol Chem. 2006 May 05; 281(18):12242-7. . View in PubMed

Histone H3 lysine 9 methyltransferase G9a is a transcriptional coactivator for nuclear receptors J Biol Chem. 2006 Mar 31; 281(13):8476-85. . View in PubMed

Differential use of functional domains by coiled-coil coactivator in its synergistic coactivator function with beta-catenin or GRIP1 J Biol Chem. 2006 Feb 10; 281(6):3389-97. . View in PubMed

A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation J Am Chem Soc. 2006 Feb 01; 128(4):1092-3. . View in PubMed

Downstream signaling mechanism of the C-terminal activation domain of transcriptional coactivator CoCoA Nucleic Acids Res. 2006; 34(9):2736-50. . View in PubMed

Interplay of Fli-I and FLAP1 for regulation of beta-catenin dependent transcription Nucleic Acids Res. 2006; 34(18):5052-9. . View in PubMed

Role of aspartate 351 in transactivation and active conformation of estrogen receptor alpha J Mol Endocrinol. 2005 Dec; 35(3):449-64. . View in PubMed

Molecular pathogenesis of chronic wounds: the role of beta-catenin and c-myc in the inhibition of epithelialization and wound healing Am J Pathol. 2005 Jul; 167(1):59-69. . View in PubMed

GAC63, a GRIP1-dependent nuclear receptor coactivator Mol Cell Biol. 2005 Jul; 25(14):5965-72. . View in PubMed

Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation Genes Dev. 2005 Jun 15; 19(12):1466-73. . View in PubMed

Role of protein methylation in regulation of transcription Endocr Rev. 2005 Apr; 26(2):147-70. . View in PubMed

Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination Proc Natl Acad Sci U S A. 2005 Mar 08; 102(10):3611-6. . View in PubMed

Hepatitis delta virus antigen is methylated at arginine residues, and methylation regulates subcellular localization and RNA replication J Virol. 2004 Dec; 78(23):13325-34. . View in PubMed

Role of the coiled-coil coactivator (CoCoA) in aryl hydrocarbon receptor-mediated transcription J Biol Chem. 2004 Nov 26; 279(48):49842-8. . View in PubMed

Human PAD4 regulates histone arginine methylation levels via demethylimination Science. 2004 Oct 08; 306(5694):279-83. . View in PubMed

Distinct LIM domains of Hic-5/ARA55 are required for nuclear matrix targeting and glucocorticoid receptor binding and coactivation J Cell Biochem. 2004 Jul 01; 92(4):810-9. . View in PubMed

Developmentally essential protein flightless I is a nuclear receptor coactivator with actin binding activity Mol Cell Biol. 2004 Mar; 24(5):2103-17. . View in PubMed

Synergistic effects of coactivators GRIP1 and beta-catenin on gene activation: cross-talk between androgen receptor and Wnt signaling pathways J Biol Chem. 2004 Feb 06; 279(6):4212-20. . View in PubMed

CoCoA, a nuclear receptor coactivator which acts through an N-terminal activation domain of p160 coactivators Mol Cell. 2003 Dec; 12(6):1537-49. . View in PubMed

The roles of protein-protein interactions and protein methylation in transcriptional activation by nuclear receptors and their coactivators J Steroid Biochem Mol Biol. 2003 Jun; 85(2-5):139-45. . View in PubMed

Study of nuclear receptor-induced transcription complex assembly and histone modification by chromatin immunoprecipitation assays Methods Enzymol. 2003; 364:284-96. . View in PubMed

Requirement for multiple domains of the protein arginine methyltransferase CARM1 in its transcriptional coactivator function J Biol Chem. 2002 Nov 29; 277(48):46066-72. . View in PubMed

Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1Coactivator-associated arginine methyltransferase. J Biol Chem. 2002 Nov 22; 277(47):44623-30. . View in PubMed

Synergistic coactivator function by coactivator-associated arginine methyltransferase (CARM) 1 and beta-catenin with two different classes of DNA-binding transcriptional activators J Biol Chem. 2002 Jul 19; 277(29):26031-5. . View in PubMed

Synergy among nuclear receptor coactivators: selective requirement for protein methyltransferase and acetyltransferase activities Mol Cell Biol. 2002 Jun; 22(11):3621-32. . View in PubMed

Effect of reproductive hormones on ovarian epithelial tumors: IEffect on cell cycle activity. Cancer Biol Ther. 2002 May-Jun; 1(3):300-6. . View in PubMed

The coactivator-associated arginine methyltransferase is necessary for muscle differentiation: CARM1 coactivates myocyte enhancer factor-2 J Biol Chem. 2002 Feb 08; 277(6):4324-33. . View in PubMed

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