Faculty

Michael R Stallcup, PhD
Michael R Stallcup, PhD
Professor of Biochemistry & Molecular Medicine
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

Relapse-associated AURKB blunts the glucocorticoid sensitivity of B cell acute lymphoblastic leukemia Proc Natl Acad Sci U S A. 2019 02 19; 116(8):3052-3061. . 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

Aberrant expression of SETD1A promotes survival and migration of estrogen receptor a-positive breast cancer cells Int J Cancer. 2018 12 01; 143(11):2871-2883. . 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

Positive regulation of ß-catenin-PROX1 signaling axis by DBC1 in colon cancer progression Oncogene. 2016 06 30; 35(26):3410-8. . 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

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

Functional interplay between p53 acetylation and H12 phosphorylation in p53-regulated transcription. Oncogene. 2012 Sep 27; 31(39):4290-301. . 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

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

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

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

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

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

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

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

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

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

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

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

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

Hormone-dependent, CARM1-directed, arginine-specific methylation of histone H3 on a steroid-regulated promoter Curr Biol. 2001 Dec 11; 11(24):1981-5. . View in PubMed

Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1 Curr Biol. 2001 Jun 26; 11(12):996-1000. . View in PubMed

Growth factors signal to steroid receptors through mitogen-activated protein kinase regulation of p160 coactivator activity J Biol Chem. 2001 Jun 22; 276(25):22177-82. . View in PubMed

Methylation of histone H3 by coactivator-associated arginine methyltransferase 1 Biochemistry. 2001 May 15; 40(19):5747-56. . View in PubMed

Enhancement of p53-dependent gene activation by the transcriptional coactivator Zac1 Oncogene. 2001 Apr 19; 20(17):2134-43. . View in PubMed

Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor Cancer Res. 2000 Nov 01; 60(21):5946-9. . View in PubMed

Interaction of the tau2 transcriptional activation domain of glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5, which localizes to both focal adhesions and the nuclear matrix Mol Biol Cell. 2000 Jun; 11(6):2007-18. . View in PubMed

Mouse Zac1, a transcriptional coactivator and repressor for nuclear receptors Mol Cell Biol. 2000 Mar; 20(5):1855-67. . View in PubMed

Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length Hum Mol Genet. 2000 Jan 22; 9(2):267-74. . View in PubMed

Co-operation between protein-acetylating and protein-methylating co-activators in transcriptional activation Biochem Soc Trans. 2000; 28(4):415-8. . View in PubMed

Constitutive activation of transcription and binding of coactivator by estrogen-related receptors 1 and 2 Mol Endocrinol. 1999 Dec; 13(12):2151-62. . View in PubMed

Modulation of transcriptional activation and coactivator interaction by a splicing variation in the F domain of nuclear receptor hepatocyte nuclear factor 4alpha1 Mol Cell Biol. 1999 Oct; 19(10):6509-22. . View in PubMed

Multiple signal input and output domains of the 160-kilodalton nuclear receptor coactivator proteins Mol Cell Biol. 1999 Sep; 19(9):6164-73. . View in PubMed

Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3 J Biol Chem. 1999 Aug 06; 274(32):22618-26. . View in PubMed

Regulation of transcription by a protein methyltransferase Science. 1999 Jun 25; 284(5423):2174-7. . View in PubMed

An additional region of coactivator GRIP1 required for interaction with the hormone-binding domains of a subset of nuclear receptors J Biol Chem. 1999 Feb 05; 274(6):3496-502. . View in PubMed

Estrogen receptor activation function 1 works by binding p160 coactivator proteins Mol Endocrinol. 1998 Oct; 12(10):1605-18. . View in PubMed

Enhancement of estrogen receptor transcriptional activity by the coactivator GRIP-1 highlights the role of activation function 2 in determining estrogen receptor pharmacology J Biol Chem. 1998 Mar 20; 273(12):6679-88. . View in PubMed

Nuclear receptor-binding sites of coactivators glucocorticoid receptor interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1): multiple motifs with different binding specificities Mol Endocrinol. 1998 Feb; 12(2):302-13. . View in PubMed

Identification of amino acids in the tau 2-region of the mouse glucocorticoid receptor that contribute to hormone binding and transcriptional activation Mol Endocrinol. 1997 Nov; 11(12):1795-805. . View in PubMed

Localization of the mouse glucocorticoid receptor-interacting protein 1 gene (Grip1) to proximal chromosome 1 by linkage analysis Mamm Genome. 1997 Aug; 8(8):620-1. . View in PubMed

Expression of a defective mouse mammary tumor virus envelope glycoprotein precursor which binds stably to GRP78 within the lumen of the endoplasmic reticulum is associated with decreased glucocorticoid-induced apoptosis in mouse lymphoma cells Cell Death Differ. 1997 May; 4(4):283-8. . View in PubMed

GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors Mol Cell Biol. 1997 May; 17(5):2735-44. . View in PubMed

A functional MRI study of mental image generation Neuropsychologia. 1997 May; 35(5):725-30. . View in PubMed

GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors Proc Natl Acad Sci U S A. 1996 May 14; 93(10):4948-52. . View in PubMed

A somatic cell genetic method for identification of untargeted mutations in the glucocorticoid receptor that cause hormone binding deficiencies Mol Endocrinol. 1995 Jul; 9(7):826-37. . View in PubMed

Growth inhibition of androgen-insensitive human prostate carcinoma cells by a 19-norsteroid derivative agent, mifepristone Prostate. 1995 Apr; 26(4):194-204. . View in PubMed

Genetic analysis of the N-terminal end of the glucocorticoid receptor hormone binding domain J Steroid Biochem Mol Biol. 1994 Oct; 51(1-2):11-9. . View in PubMed

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Phenylalanine-780 near the C-terminus of the mouse glucocorticoid receptor is important for ligand binding affinity and specificity Mol Endocrinol. 1994 Apr; 8(4):422-30. . View in PubMed

Relationship between defective mouse mammary tumor virus envelope glycoprotein synthesis and GRP78 synthesis in glucocorticoid-treated mouse lymphoma cellsEvidence for translational control of GRP78 synthesis. J Biol Chem. 1993 Apr 05; 268(10):7482-8. . View in PubMed

Maturation of mouse mammary tumor virus envelope protein is blocked by a specific point mutation Virology. 1992 Jul; 189(1):393-6. . View in PubMed

A novel intermediate in processing of murine leukemia virus envelope glycoproteinsProteolytic cleavage in the late Golgi region. J Biol Chem. 1992 Apr 05; 267(10):7060-5. . View in PubMed

Cellular and viral components that mediate glucocorticoid-regulated processing of retroviral envelope proteins Cell Biophys. 1991 Oct-Dec; 19(1-3):93-108. . View in PubMed

Characterization of oligosaccharide chains on mouse mammary tumor virus envelope proteins and the implications for the mechanism of their glucocorticoid regulated processing Mol Endocrinol. 1990 May; 4(5):749-57. . View in PubMed

Glucocorticoid-dependent maturation of mouse mammary tumor virus glycoproteins in mouse lymphoma cells: isolation of variants with constitutive viral protein maturation and normal glucocorticoid receptor function Mol Endocrinol. 1990 Feb; 4(2):341-8. . View in PubMed

A role for divalent cations in specifying the start site for transcription from chromatin templates in vitro J Biol Chem. 1988 Jul 05; 263(19):9550-6. . View in PubMed

Optimized reaction conditions and specific inhibitors for initiation of transcription by RNA polymerase II in nuclei from cultured mammalian cells J Biol Chem. 1988 Mar 05; 263(7):3513-20. . View in PubMed

Glucocorticoid-resistant lymphoma cell variants that contain functional glucocorticoid receptors Mol Cell Biol. 1987 Dec; 7(12):4211-7. . View in PubMed

Mouse lymphoma cell variants with genetically dominant alterations in the maturation of viral glycoproteins Mol Endocrinol. 1987 Jul; 1(7):491-9. . View in PubMed

Glucocorticoid-dependent maturation of viral proteins in mouse lymphoma cells: isolation of defective and hormone-independent cell variants Somat Cell Mol Genet. 1987 Mar; 13(2):131-43. . View in PubMed

Hormonal regulation of transcription of rDNA: use of nucleoside thiotriphosphates to measure initiation in isolated nuclei Nucleic Acids Res. 1984 Nov 12; 12(21):8115-28. . View in PubMed

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Isolation of recombinant bacteriophage containing male-specific mouse DNA Mol Gen Genet. 1983; 190(1):80-4. . View in PubMed

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