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M. Alexander Monroy

 

M. Alexandra Monroy, PhD

 

Assistant Professor, Anatomy and Cell Biology

Assistant Professor, Surgery

Telephone:  215-707-1898

Fax:  215-707-8820

Email:  amonroy@temple.edu

 

Department of Anatomy and Cell Biology

Department of Surgery

 

Educational Background:

 

Rutgers University, Newark, NJ

BA, Biology, 1989

 

Boston University School of Medicine, Boston, MA

PhD, Pathology/Immunology, 1997

 

Department of Pathology, Washington University School of Medicine, St. Louis, MO

Postdoctoral fellowship, 1997-1999

 

Department of Pharmacology, St. Louis University School of Medicine, St. Louis, MO

Postdoctoral fellowship, 1999-2002

 

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Research Interests:

 

Dr. Monroy's overall research interest is to understand the signaling mechanisms involved in specific gene regulation.

 

Regulation of the Prostate Specific Antigen (PSA) Promoter by the cofactor SRCAP.

 

The expression of PSA is induced by androgens and regulated by the androgen receptor (AR) which is a nuclear receptor.  Recently many cofactors implicated in the transcriptional activation by nuclear receptors have been identified and include factors that alter chromatin structure.    Local alteration of chromatin structure is necessary to facilitate promoter accessibility.  Distinct multiprotein complexes exist that affect local chromatin structure through nucleosome interaction and modulation. The novel protein SRCAP (SNF2-related CBP Activator Protein) was identified by virtue of its interaction with the histone acetyl transferase, CBP (CREB Binding Protein).  SRCAP has an ATPase domain and is believed to be involved in chromatin remodeling.  It functions as a coactivator for various nuclear receptors including the androgen receptor. The goal of this project is to determine the role that SRCAP plays in PSA gene regulation induced by androgen.

 

Regulation of macrophage inflammatory marker expression by ligands of peroxisome proliferator-activated receptor- gamma (PPAR gamma ).

 

PPAR gamma is a ligand-activated transcription factor that belongs to the nuclear receptor superfamily.  It is required for adipocyte differentiation, and it regulates the expression of many genes involved in metabolism.  However, in macrophages it has been shown to trans-repress the expression of inflammatory genes such as TNFalpha, iNOS and COX-2 which are induced by lipopolysaccharide (LPS).  It is believed that PPAR gamma inhibits gene expression in a DNA-binding independent manner. It inhibits signaling pathways such as NF-kappaB and AP-1 which are required for inflammatory gene activation.  Recently it was shown that activation of PPAR gamma in macrophages retains corepressor complexes at the iNOS promoter and prevents expression of this gene in response to LPS.  Using chromatin immunoprecipitation (ChIP) assays we are examining histone modifications induced by PPAR gamma activation at various promoters.  The goal of this project is to determine the mechanisms by which PPAR gamma activation downregulates expression of inflammatory genes in splenic macrophages in a murine trauma model, and in human monocyte cell lines.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

21826405. Breslow JM, Monroy MA, Daly JM, Meissler JJ, Gaughan J, Adler MW, Eisenstein TK, Morphine, but not trauma, sensitizes to systemic Acinetobacter baumannii infection. J Neuroimmune Pharmacol 6:4(551-65)2011 Dec

21503878. Singh M, Del Carpio-Cano FE, Monroy MA, Popoff SN, Safadi FF, Homeodomain transcription factors regulate BMP-2-induced osteoactivin transcription in osteoblasts. J Cell Physiol 227:1(390-9)2012 Jan

20504359. Rough JJ, Monroy MA, Yerrum S, Daly JM, Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells. J Ovarian Res 3:(13)2010 May 26

20432434. Slupianek A, Yerrum S, Safadi FF, Monroy MA, The chromatin remodeling factor SRCAP modulates expression of prostate specific antigen and cellular proliferation in prostate cancer cells. J Cell Physiol 224:2(369-75)2010 Aug

19167980. Rough J, Engdahl R, Opperman K, Yerrum S, Monroy MA, Daly JM, beta2 Adrenoreceptor blockade attenuates the hyperinflammatory response induced by traumatic injury. Surgery 145:2(235-42)2009 Feb

17532302. Engdahl R, Monroy MA, Daly JM, 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) mediates repression of TNF-alpha by decreasing levels of acetylated histone H3 and H4 at its promoter. Biochem Biophys Res Commun 359:1(88-93)2007 Jul 20

17510607. Monroy MA, Opperman KK, Pucciarelli M, Yerrum S, Berg DA, Daly JM, THE PPARgamma ligand 15d-PGJ2 modulates macrophage activation after injury in a murine trauma model. Shock 28:2(186-91)2007 Aug

14500758. Monroy MA, Schott NM, Cox L, Chen JD, Ruh M, Chrivia JC, SNF2-related CBP activator protein (SRCAP) functions as a coactivator of steroid receptor-mediated transcription through synergistic interactions with CARM-1 and GRIP-1. Mol Endocrinol 17:12(2519-28)2003 Dec

11856642. Monroy MA, Ross FP, Teitelbaum SL, Sands MS, Abnormal osteoclast morphology and bone remodeling in a murine model of a lysosomal storage disease. Bone 30:2(352-9)2002 Feb

11581372. Xu X, Chackalaparampil I, Monroy MA, Cannella MT, Pesek E, Chrivia J, Yaciuk P, Adenovirus DNA binding protein interacts with the SNF2-related CBP activator protein (SrCap) and inhibits SrCap-mediated transcription. J Virol 75:21(10033-40)2001 Nov

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