Michael Ostrowski

Focus

Regulation of transcriptional networks

Research interests

The Ostrowski lab has a long-standing interest in understanding how signaling pathways elicit selective, persistent changes in gene transcription in mammalian cells. We have three ongoing projects funded by NIH ( 5R01CA053271-13, 2R01AR044719-05A1; 1P01CA097189, see: http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen).  One project is centered on the ras/Erk/ets signaling pathway in cancer cells (abnormal signaling project) and one on the rac/p38 MAP kinase/microphthalmia transcription factor pathway during normal bone development and bone remodeling that occurs throughout life (normal signaling project), and a new project studies the role of the ras/ets pathway in the breast tumor microenvironment.

1. Abnormal Signaling: Persistent Activation of Gene Expression by the ras/ets Signaling Pathway in Inflammation and Tumorigenesis

2. Normal Signaling: The Role of the microphthalmia Transcription Factor in Osteoclast Differentiation

3. Genetic Analysis of the Tumor Microenvironment in Breast Cancer Progression.

As part of a multidisciplinary collaboration that includes faculty members in 4 colleges and 7 departments at OSU, we are taking a genetic approach to study the effect of gene action from the tumor microenvironment on breast cancer progression.  Collaborators on these projects include Gustavo Leone, Charis, Eng, Tom Rosol, Aki Otoshi, Stan Lemeshow, Soledad Fernandez, Lei Shen and Fred Cope.  This work was recently funded as a new Program Project Grant by NCI.

4. Analysis of Redundant Roles of ets-1 and ets-2 During Mouse Development

This project is a collaboration with Bob Oshima (Burnham Insitutute, LaJolla).

Publications

• Svensson S, Jirstrom K, Ryden L, Roos G, Emdin S, Ostrowski MC, Landberg G. ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis. Oncogene. 2005 Jun 23;24(27):4370-9.
• Ganesan LP, Wei G, Pengal RA, Moldovan L, Moldovan N, Ostrowski MC, Tridandapani S. The serine/threonine kinase Akt Promotes Fc gamma receptor-mediated phagocytosis in murine macrophages through the activation of p70S6 kinase. J Biol Chem. 2004 Dec 24;279(52):54416-25. Epub 2004 Oct 12.
• Sankar U, Patel K, Rosol TJ, Ostrowski MC. RANKL Coordinates Cell Cycle Withdrawal and Differentiation in Osteoclasts Through the Cyclin-Dependent Kinase Inhibitors p27KIP1 and p21CIP1. J Bone Miner Res. 2004 Aug;19(8):1339-48.
• Wei G, Guo J, Doseff AI, Kusewitt DF, Man AK, Oshima RG, Ostrowski MC. Activated Ets2 is required for persistent inflammatory responses in the motheaten viable model. J Immunol. 2004 Jul 15;173(2):1374-9.
• Cao X, Wei G, Fang H, Guo J, Weinstein M, Marsh CB, Ostrowski MC, Tridandapani S. The inositol 3-phosphatase PTEN negatively regulates Fc gamma receptor signaling, but supports Toll-like receptor 4 signaling in murine peritoneal macrophages. J Immunol. 2004 Apr 15;172(8):4851-7.
• Petrovic N, Bhagwat SV, Ratzan WJ, Ostrowski MC, Shapiro LH. CD13/APN transcription is induced by Ras/MapK mediated phosphorylation of Ets-2 in activated endothelial cells. J Biol Chem. 2003 Dec 5;278(49):49358-68. Epub 2003 Sep 24.
• Cassady AI, Luchin A, Ostrowski MC, Hume DA Regulation of the murine TRACP gene promoter. J Bone Miner Res. 2003 Oct;18(10):1901-4.
• Wei G, Schaffner AE, Baker KM, Mansky KC, Ostrowski MC. Ets-2 interacts with co-repressor BS69 to repress target gene expression. Anticancer Res. 2003 May-Jun;23(3A):2173-8.
• So H, Rho J, Jeong D, Park R, Fisher DE, Ostrowski MC, Choi Y, Kim N. Microphthalmia transcription factor and PU.1 synergistically induce the leukocyte receptor OSCAR gene expression. J Biol Chem. 2003 Jun 27;278(26):24209-16. Epub 2003 Apr 13.
• Baker KM, Wei G, Schaffner AE, Ostrowski MC. Ets-2 and components of mammalian SWI/SNF form a repressor complex that negatively regulates the BRCA1 promoter. J Biol Chem. 2003 May 16;278(20):17876-84. Epub 2003 Mar 10.
• Wu L, de Bruin A, Saavedra HI, Starovic M, Trimboli A, Yang Y, Opavska J, Wilson P, Thompson JC, Ostrowski MC, Rosol TJ, Woollett LA, Weinstein M, Cross JC, Robinson ML, Leone G. Extra-embryonic function of Rb is essential for embryonic development and viability. Nature. 2003 Feb 27;421(6926):942-7.
• Ghosh D, Ezashi T, Ostrowski MC, Roberts RM. A Central Role for Ets-2 in the Transcriptional Regulation and Cyclic Adenosine 5'-Monophosphate Responsiveness of the Human Chorionic Gonadotropin-beta Subunit Gene. Mol Endocrinol. 2003 Jan;17(1):11-26.
• Sasmono RT, Oceandy D, Pollard JW, Tong W, Pavli P, Wainwright BJ, Ostrowski MC, Himes SR, Hume DA. A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse. Blood. 2003 Feb 1;101(3):1155-63.
• Weng LP, Brown JL, Baker KM, Ostrowski MC, Eng C. PTEN blocks insulin-mediated ETS-2 phosphorylation through MAP kinase, independently of the phosphoinositide 3-kinase pathway. Hum Mol Genet. 2002 Jul 15;11(15):1687-96.
• Mansky KC, Sulzbacher S, Purdom G, Nelsen L, Hume DA, Rehli M, Ostrowski MC. The microphthalmia transcription factor and the related helix-loop-helix zipper factors TFE-3 and TFE-C collaborate to activate the tartrate-resistant acid phosphatase promoter. J Leukoc Biol. 2002 Feb;71(2):304-10.
• Mansky KC, Marfatia K, Purdom GH, Luchin A, Hume DA, Ostrowski MC. The microphthalmia transcription factor (MITF) contains two N-terminal domains required for transactivation of osteoclast target promoters and rescue of mi mutant osteoclasts. J Leukoc Biol. 2002 Feb;71(2):295-303.
• Mansky KC, Sankar U, Han J, Ostrowski MC. Microphthalmia transcription factor (MITF) is a target of the p38 MAPK pathway in response to Receptor Activator of NF-KB ligand signaling. J. Biol Chem. 2002 Mar 29;277(13):11077-83.
• Luchin A, Suchting S, Merson T, Rosol TJ, Hume DA, Cassady AI, Ostrowski MC. Genetic and physical interactions between microphthalmia transcription factor and PU.1 are necessary for osteoclast gene expression and differentiation. J Biol Chem. 2001 Sep 28;276(39):36703-10.
• Angel NZ, Walsh N, Forwood MR, Ostrowski MC, Cassady AI, Hume DA. Transgenic mice overexpressing tartrate-resistant acid phosphatase exhibit an increased rate of bone turnover. J Bone Miner Res. 2000 Jan;15(1):103-10.
• Luchin A, Purdom G, Murphy K, Clark MY, Angel N, Cassady AI, Hume DA, Ostrowski MC. The microphthalmia transcription factor regulates expression of the tartrate-resistant acid phosphatase gene during terminal differentiation of osteoclasts. J Bone Miner Res. 2000 Mar;15(3):451-60.
• Smith JL, Schaffner AE, Hofmeister JK, Hartman M, Wei G, Forsthoefel D, Hume DA, Ostrowski MC. ets-2 is a target for an akt (Protein kinase B)/jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice. Mol Cell Biol. 2000 Nov;20(21):8026-34.
• Kelley TW, Graham MM, Doseff AI, Pomerantz RW, Lau SM, Ostrowski MC, Franke TF, Marsh CB. Macrophage colony-stimulating factor promotes cell survival through Akt/protein kinase B. J Biol Chem. 1999 Sep 10;274(37):26393-8.
• Lichanska AM, Browne CM, Henkel GW, Murphy KM, Ostrowski MC, McKercher SR, Maki RA, Hume DA. Differentiation of the mononuclear phagocyte system during mouse embryogenesis: the role of transcription factor PU.1. Blood. 1999 Jul 1;94(1):127-38.
• Rehli M, Lichanska A, Cassady AI, Ostrowski MC, Hume DA. TFEC is a macrophage-restricted member of the microphthalmia-TFE subfamily of basic helix-loop-helix leucine zipper transcription factors. J Immunol. 1999 Feb 1;162(3):1559-65.
• Rehli M, Den Elzen N, Cassady AI, Ostrowski MC, Hume DA. Cloning and characterization of the murine genes for bHLH-ZIP transcription factors TFEC and TFEB reveal a common gene organization for all MiT subfamily members. Genomics. 1999 Feb 15;56(1):111-20.