Home > Directory > Faculty Directory > Michael Ostrowski
Professor and Chair
Ph.D. - University of South Carolina
Post Doctoral - National Institutes of Health, Bethesda, MD
Our lab has a long-standing interest in understanding how signaling pathways elicit selective changes in gene transcription in mammalian cells. 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 pathways during normal bone development and bone remodeling that occurs throughout life (normal signaling projects). We use a combination of genetic mouse models, molecular genetics, biochemistry and cell biology to attack these problems.
Most recently, we have become interested in understanding interactions between signaling pathways locating in the different cell types involved in these complex biological processes of cancer cell progression and normal cellular differentiation. For example, a breast tumor is composed not only of the epithelial-cell derived tumor cell, but also stromal cells, endothelial cells, and immune cells including macrophages, B-cells and T-cells. It is the interaction of these cell types through complex signaling networks that are likely to be important for tumor cell progression and metastasis, and not just the action of individual signaling pathways within the epithelial tumor cell. Understanding and targeting such intercellular networks of communication holds great promise for new advances in the diagnosis and treatment of cancer.
Using mouse genetic techniques, we have begun removing gene of interest within specific cell compartments in breast tumor models, and are subsequently monitoring the effect of these mutations both on other cell types in the tumor microenvironment as well as on overall tumor growth and malignant progression. Eventually we will make mutations in different gene pathways within different cell compartments within the same tumor.
- Baran CP, Fischer SN, Nuovo GJ, Kabbout MN, Hitchcock CL, Bringardner BD, McMaken S, Newland CA, Cantemir-Stone CZ, Phillips GS, Ostrowski MC and Marsh CB (2011) "The Transcription Factor ets-2 Plays an Important Role in the Pathogenesis of Pulmonary Fibrosis" Am J Respir Cell Mol Biol. May 11. [Epub ahead of print]
- Wallace JA, Li F, Leone G and Ostrowski MC (2011) "Pten in the breast tumor microenvironment: modeling tumor-stroma coevolution" Cancer Res. 71(4):1203-7.
- Trikha P, Sharma N, Opavsky R, Reyes A, Pena C, Ostrowski MC, Roussel MF and Leone G (2010) "E2F1-3 Are Critical for Myeloid Development" J Biol Chem. 286(6):4783-95.
- Ostrowski MC (2010) "A new role for OPG: Putting RANKL in its place" J Bone Miner Res. 25(9):1905-6.
- Acharyya S, Sharma SM, Cheng AS, Ladner KJ, He W, Kline W, Wang H, Ostrowski MC, Huang TH, Guttridge DC (2010) "TNF inhibits Notch-1 in skeletal muscle cells by Ezh2 and DNA methylation mediated repression: implications in duchenne muscular dystrophy" PLoS One. 5(8):e12479.
- Godlewski J, Nowicki MO, Bronisz A, Nuovo G, Palatini J, De Lay M, Van Brocklyn J, Ostrowski MC, Chiocca EA and Lawler SE (2010) "MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells" Mol Cell. 37(5):620-32.
- Wang H, Karikomi M, Naidu S, Rajmohan R, Caserta E, Chen HZ, Rawahneh M, Moffitt J, Stephens JA, Fernandez SA, Weinstein M, Wang D, Sadee W, La Perle K, Stromberg P, Rosol TJ, Eng C, Ostrowski MC, Leone G (2010) "Allele-specific tumor spectrum in Pten knockin mice" Proc Natl Acad Sci U S A 107(11):5142-7.
- Zabuawala T, Taffany DA, Sharma SM, Merchant A, Adair B, Srinivasan R, Rosol TJ, Fernandez S, Huang K, Leone G, Ostrowski MC (2010) "An ets2-driven transcriptional program in tumor-associated macrophages promotes tumor metastasis" Cancer Res. 70(4):1323-33.
- Srinivasan R, Zabuawala T, Huang H, Zhang J, Gulati P, Fernandez S, Karlo JC, Landreth GE, Leone G and Ostrowski MC (2009) "Erk1 and Erk2 regulate endothelial cell proliferation and migration during mouse embryonic angiogenesis" PLoS One 4(12):e8283.
- Kim Y, Wallace J, Li F, Ostrowski M and Friedman A (2009) "Transformed epithelial cells and fibroblasts/myofibroblasts interaction in breast tumor: a mathematical model and experiments" J Math Biol. 61(3):401-21.
- Trimboli AJ, Cantemir-Stone CZ, Li F, Wallace JA, Merchant A, Creasap N, Thompson JC, Caserta E, Wang H, Chong JL, Naidu S, Wei G, Sharma SM, Stephens JA, Fernandez SA, Gurcan MN, Weinstein MB, Barsky SH, Yee L, Rosol TJ, Stromberg PC, Robinson ML, Pepin F, Hallett M, Park M, Ostrowski MC and Leone G (2009) "Pten in stromal fibroblasts suppresses mammary epithelial tumours" Nature 461(7267):1084-91.
- Eng C, Leone G, Orloff MS and Ostrowski MC (2009) "Genomic alterations in tumor stroma" Cancer Res. 69(17):6759-64.
- Pan F, Yu H, Dang EV, Barbi J, Pan X, Grosso JF, Jinasena D, Sharma SM, McCadden EM, Getnet D, Drake CG, Liu JO, Ostrowski MC and Pardoll DM (2009) "Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells" Science 325(5944):1142-6.
- Kampfrath T, Deiuliis JA, Moffatt-Bruce SD, Anderson J, Sun Q, Wood K, Ostrowski MC and Rajagopalan S (2009) "A mouse model of yellow fluorescent protein (YFP) expression in hematopoietic cells to assess leukocyte-endothelial interactions in the microcirculation" Microvasc Res. 78(3):294-300.
- Wei G, Srinivasan R, Cantemir-Stone CZ, Sharma SM, Santhanam R, Weinstein M, Muthusamy N, Man AK, Oshima RG, Leone G and Ostrowski MC (2009) "Ets1 and Ets2 are required for endothelial cell survival during embryonic angiogenesis" Blood 114(5):1123-30.
- Sharma SM, Sif S, Ostrowski MC and Sankar U (2009) "Defective co-activator recruitment in osteoclasts from microphthalmia-oak ridge mutant mice" J Cell Physiol. 220:(1)230-7.
- Sun Q, Yue P, Deiuliis JA, Lumeng CN, Kampfrath T, Mikolaj MB, Cai Y, Ostrowski MC, Lu B, Parthasarathy S, Brook RD, Moffatt-Bruce SD, Chen LC and Rajagopalan S (2009) "Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity" Circulation 119(4):538-46.
- Joshi T, Ganesan LP, Cheney C, Ostrowski MC, Muthusamy N, Byrd JC and Tridandapani S (2009) "The PtdIns 3-kinase/Akt pathway regulates macrophage-mediated ADCC against B cell lymphoma" PLoS ONE 4(1):e4208.
- Sun Y, Ishibashi M, Seimon T, Lee M, Sharma SM, Fitzgerald KA, Samokhin AO, Wang Y, Sayers S, Aikawa M, Jerome WG, Ostrowski MC, Bromme D, Libby P, Tabas IA, Welch CL and Tall AR (2009) "Free Cholesterol Accumulation in Macrophage Membranes Activates Toll-Like Receptors and p38 Mitogen-Activated Protein Kinase and Induces Cathepsin K" Circ Res. 104(4):455-65.
- Lin HJ, Zuo T, Lin CH, Kuo CT, Liyanarachchi S, Sun S, Shen R, Deatherage DE, Potter D, Asamoto L, Lin S, Yan PS, Cheng AL, Ostrowski MC and Huang TH (2008) "Breast cancer-associated fibroblasts confer AKT1-mediated epigenetic silencing of Cystatin M in epithelial cells" Cancer Res 68(24):10257-66.
- Aliprantis AO, Ueki Y, Sulyanto R, Park A, Sigrist KS, Sharma SM, Ostrowski MC, Olsen BR and Glimcher LH (2008) "NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism" J Clin Invest 118(11):377-89.
- Hou Y, Li F, Karin M and Ostrowski MC (2008) "Analysis of the IKKbeta/NF-kappaB signaling pathway during embryonic angiogenesis" Dev Dyn 237(10):2926-35.
- Mosaliganti K, Janoos F, Irfanoglu O, Ridgway R, Machiraju R, Huang K, Saltz J, Leone G and Ostrowski M (2008) "Tensor classification of N-point correlation function features for histology tissue segmentation" Med Image Anal 13(1):156-66.
- Hume DA, Sasmono R, Himes SR, Sharma SM, Bronisz A, Constantin M, Ostrowski MC and Ross IL (2008) "The Ewing sarcoma protein (EWS) binds directly to the proximal elements of the macrophage-specific promoter of the CSF-1 receptor (csf1r) gene" J Immunol 180(10):6733-42.
- Crotti TN, Sharma SM, Fleming JD, Flannery MR, Ostrowski MC, Goldring SR and McHugh KP (2008) "PU.1 and NFATc1 mediate osteoclastic induction of the mouse beta3 integrin promoter" J Cell Physiol 215(3):636-44.
- Trimboli AJ, Fukino K, deBruin A, Wei G, Shen L, Tanner SM, Creasap N, Rosol TJ, Robinson ML, Eng C, Ostrowski MC and Leone G (2008) "Direct evidence for epithelial-mesenchymal transitions in breast cancer" Cancer Res 68(3):937-45.
- Sussan TE, Yang A, Li F and Ostrowski MC (2008) "Trisomy represses Apc(Min)-mediated tumours in mouse models of Down's syndrome" Nature 451(7174):73-5.
- Opavsky R, Wang SH, Trikha P, Raval A, Huang Y, Wu YZ, Rodriguez B, Keller B, Liyanarachchi S, Wei G, Davuluri RV, Weinstein M, Felsher D, Ostrowski M, Leone G and Plass C (2007) "CpG island methylation in a mouse model of lymphoma is driven by the genetic configuration of tumor cells" PLoS Genet 3(9):1757-69.
- Hu R, Sharma SM, Bronisz A, Srinivasan R, Sankar U and Ostrowski MC (2007) "Eos, MITF, and PU.1 Recruit Corepressors to Osteoclast-Specific Genes in Committed Myeloid Progenitors" Mol Cell Biol 27(11):4018-27.
- Sharma SM, Bronisz A, Hu R, Patel K, Mansky KC, Sif S and Ostrowski MC (2007) "MITF and PU.1 recruit p38 MAPK and NFATc1 to target genes during osteoclast differentiation" J Biol Chem 282(3):1891-904.
- Meadows NA, Sharma SM, Faulkner GJ, Ostrowski MC, Hume DA and Cassady AI (2007) "The expression of Clcn7 and Ostm1 in osteoclasts is coregulated by microphthalmia transcription factor" J Biol Chem 282(3):1891-904.
- Sharma SM, Hu R, Bronisz A, Meadows N, Lusby T, Fletcher B, Hume DA, Cassady AI and Ostrowski MC (2006) "Genetics and genomics of osteoclast differentiation: integrating cell signaling pathways and gene networks. Crit Rev Eukaryot Gene Expr 16(3):253-77.
- Anghelina M, Moldovan L, Zabuawala T, Ostrowski MC and Moldovan NI (2006) "A subpopulation of peritoneal macrophages form capillarylike lumens and branching patterns in vitro" J Cell Mol Med 10(3):708-15.
- Bronisz A, Sharma SM, Hu R, Godlewski J, Tzivion G, Mansky KC and Ostrowski MC (2006) "MITF Interactions with 14-3-3 Modulate Differentiation of Committed Myeloid Precursors" Mol Biol Cell 17(9):3897-906.
- Pengal RA, Ganesan LP, Wei G, Fang H, Ostrowski MC and Tridandapani S (2006) "Lipopolysaccharide-induced production of interleukin-10 is promoted by the serine/threonine kinase Akt" Mol Immunol 43(10):1557-64.
- Svensson S, Jirstrom K, Ryden L, Roos G, Emdin S, Ostrowski MC and Landberg G (2005) "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 24(27):4370-9.
- Cao X, Wei G, Fang H, Guo J, Weinstein, M, Marsh, CB, Ostrowski MC and Tridandapani S (2004) "The Inositol 3-Phosphatase PTEN Negatively Regulates FcgR Signaling, but Supports TLR4 Signaling in Murine Peritoneal Macrophages" J Immunol 172(8):4851-7.
- Sankar U, Patel, K, Rosol TJ and Ostrowski MC (2004) "RANKL co-ordinates cell cycle withdrawal and differentiation in osteoclasts through the cyclin-dependent kinase inhibitors p27KIP1 and p21CIP1" J Bone Min Res 19(8):1339-48.