Marsh Lab

Clay Marsh, MD Division of Pulmonary Department of Internal Medicine The Ohio State University 465/455 Davis HLRI 473 West 12th Avenue Columbus, Ohio 43210-1252 Phone: (614) 247-7662 E-mail: clay.marsh@osumc.edu
Interest and Subspecialty
Our laboratory focuses on the role of the growth factor macrophage colony-stimulating factor (M-CSF) and mononuclear phagocytes in health and disease. We are interested in understanding the native signaling pathways and proteins responsible for mononuclear phagocyte survival and differentiation and apply this information to understand how this is dysregulated in diseases, including lung disease, heart disease and cancer. We are also interested in the mechanisms of repair, remodeling and angiogenesis related to mononuclear phagocytes in pulmonary fibrosis. Translationally, we are interested in lung fibrosis, emphysema, and cancer. In addition, because of the important role of these cells in inflammation, we have been involved with studies in coronary artery disease and transplant vascular disease. Lastly, we found an important role for mononuclear phagocytes in the regulation of VEGF production and biological activity and are interested in how this may apply to cancer growth and spread.
We are also dedicated to growing translational research and personalized/predictive health care in the areas of critical care, respiratory disease, trauma, burn and wound healing and explore the influence of Stress/Depression on driving advanced lung and critical care disease. Our laboratory is divided into five modules related to monocyte/macrophage biology:
1) Signaling and cell survival/differentiation 2) Lung repair, remodeling and fibrosis 3) Angiogenesis 4) The role of stress/depression in lung disease and cancer 5) MicroRNA in lung and critical care disease
My goal is to help people in our program grow and become independent scientists/investigators. We hope to uncover basic mechanisms underlying mononuclear phagocyte-induced inflammation using a phenotype-based patient-centered approach and translate these findings to novel approaches to identifying, classifying, treating and preventing disease.
Publications
1. Tridandapani S, Wardrop R, Baran C, Wang Y, Opalek, JM, Caligiuri MA, Marsh CB. TFG-?1 Suppresses Myeloid Fc??Receptor Function by Regulating the Expression and Function of the Common ?-Subunit. 2003. Journal of Immunology 170: 4572-4577.
2. Eubank T, Galloway M, Montague CM, Waldman WJ, Marsh CB. M-CSF induces vascular endothelial growth factor production and angiogenic activity from human monocytes. 2003. The Journal of Immunology 171:2637-2643.
3. Baran CP, Tridandapani S, Helgason CD, Humphries RK, Krystal G, Marsh CB. The Inositol 5’-Phosphatase SHIP-1 and the Src Kinase Lyn Negatively Regulate Macrophage Colony-stimulating Factor-Induced Akt Activity. 2003. Journal of Biological Chemistry Oct 3; 278 (40):38628-38636.
4. Jin M, Opalek J, Marsh C, and Wu H. Proteome Comparison of Alveolar Macrophages with Monocytes Reveals Distinct Protein Characteristics. 2004. American Journal of Respiratory and Molecular Cell Biology. May 6 (Epub ahead of print). Sep;31(3):322-9.
5. Baran C, Graham MM, Tridandapani S, Marsh CB, The role of ROS and RNS in monocyte survival, Current Pharmaceutical Design 2004. 10:855-866.
6. Wang Y, Tridandapani S, Marsh CB. SHIP2 is Recruited to the Cell Membrane upon M-CSF Stimulation and Regulates M-CSF-Induced Signaling 2004. The Journal of Immunology, Dec 1;173(11):6820-30.
7. Eubank TD, Roberts R, Galloway M, Wang Y, Cohn DE, Marsh CB. GM-CSF induces expression of soluble VEGF receptor-1 from human monocytes and inhibits angiogenesis in mice. 2004. Immunity, Dec;21(6):831-42.
8. Wu HM, Jin M, Marsh CB. Towards functional proteomics of alveolar macrophages. 2005. American Journal of Physiology: Lung Cellular and Molecular Physiology. 2005. Apr;288(4):L585-95.
9. Jing A, Maturu A, Johnson W, Wang Y, Marsh CB and Tridandapani S. The Inositol Phosphatase SHIP-2 Downregulates Fc?R-Mediated Phagocytosis in Murine Macrophages Independently of SHIP-1. 2005. Blood September 22, 2005.
10. Ai J, Maturu A, Johnson W, Wang Y, Marsh CB, Tridandapani S. The inositol phosphatase SHIP-2 down-regulates Fc?R-mediated phagocytosis in murine macrophages independently of SHIP-1. Blood. 2006 Jan 15;107(2):813-20.
11. Bhatt N, Baran CP, Magro C, Allen JN, Marsh CB. Promising pharmacologic innovations in treating pulmonary fibrosis. Current Opinions in Pharmacology. 2006. Jun;6(3):284-92.
12. Magro C, Waldman J, Opalek J, Allen J, Marsh CB. Idiopathic pulmonary fibrosis: is it really a forme fruste of limited autoimmune disease related to anti-endothelial cell antibodies? A hypothesis. Human Immunology 2006, 67(4-5):284-97.
13. Montague CR, Hunter MG, Gavrilin MA, Philllips GS, Goldschmidt-Clermont PJ, Marsh CB. Activation of estrogen receptor-? reduces aortic smooth muscle cell differentiation. Circualtion Research. 2006, 1:99(5):477-84.
14. Wang Y, Ziegler MM, Lam GK, Hunter MG, Eubank TD, Khramtsov VV, Tridandapani S, Marsh CB. The Role of the NADPH Oxidase Complex, p38 MAPK, and Akt in Regulating Human Monocyte/Macrophage Survival. American Journal of Respiratory Cell and Molecular Biology. 2006, Jan;36(1):68-77. Epub 2006 Aug 24.
15. Jin M, Diaz PT, Bourgeois T, Eng C, Marsh CB, Wu H. Two-dimensional gel proteome reference map of blood monocytes. Proteome Science. 2006 Sep 1;4:16.
16. Yang EV, Sood AK, Chen M, Li Y, Eubank TD, Marsh CB, Jewell S, Flavahan NA, Morrison C, Yeh PE, Lemeshow S, Glaser R. Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells. Cancer Research. 2006 Nov 1;66(21):10357-64.
17. Baran CP, Opalek JM, McMaken S, Newland CA, O’Brien Jr JM, Hunter MG, Bringardner BD, Monick MM, Brigstock DR, Stromberg PC, Hunninghake GW and Marsh CB. Important roles for M-CSF, CCL2 and mononuclear phagocytes in the pathogenesis of pulmonary fiborsis. Am J Respir Crit Care Med. 2007 Apr 12 (Epub ahead of print).
18. Opalek JM, Ali NA, Lobb JM, Hunter MG, Marsh CB. Alveolar Macrophages Lack CCR2 Expression and do not Migrate to CCL2. Journal of Inflammation. 4(1):19, 2007.
19. Bringardner BD, Baran CP, Eubank TD, Marsh CB. The role of inflammation in the pathogenesis of idiopathic pulmonary fibrosis. Antioxid Redox Signal. 2008 Feb;10(2):287-302.
20. Hunter M, Wang Y, Eubank T, Baran C, Nana-Sinkam P, Marsh C. Survival of monocytes and macrophages and their role in health and disease. Invited review; Frontiers in Bioscience 2008, in press. 21. Crawford, M., Brawner, E., Batte, K., Yu, L., Hunter, MG, Otterson, GA, Nuovo, G., Marsh, CB, Nana-Sinkam, SP.MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines. Biochem Biophys Res Commun. 2008 Sep 5;373(4):607-12. 22. Nana-Sinkam, S.P., Hunter, M.G., Nuovo, G.J., Schmittgen, T.D., Gelinas, R., Galas, D., Marsh, C.B., Integrating the microRNome into the study of lung disease, American Journal of Respiratory and Critical Care Medicine, 2008, in press
23. Piper-Hunter M, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee M-L T, Schmittgen TD, Nana-Sinkam SP, Jarjoura D , Marsh CB. "Detection of microRNA Expression in Human Peripheral Blood Microvesicles." PLos One 2008, in press
24. Aguda B, Kim Y, Piper-Hunter M, Friedman A, Marsh CB. MicroRNA Regulation of a Cancer Network: Consequences of the Feedback Loops Involving miR-17-92, E2F, and Myc, PNAS 2008, in press.

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