James Michael Shipley, Ph.D.

Assistant Professor of Medicine and Cell Biology & Physiology

EDUCATION/TRAINING

Southern Illinois University at Edwardsville, B.S. 1986 Biology
St. Louis University, St. Louis MO, Ph.D. 1992 Biochemistry and Molecular Biology

EMPLOYMENT EXPERIENCE

1984 - 1986 Southern Illinois University at Edwardsville
(Studied the effect of 5-azacytidine on fetal hemoglobin expression in K562 cells under the direction of Dr. Paul Wanda). 1985 Summer internship at McDonnell Douglas in the "Electrophoresis Operations in Space" program.
1987 - 1992 Ph.D. Dissertation research under the direction of Dr. William S. Sly, St. Louis University School of Medicine
1992 - 1996 Postdoctoral Fellow under the direction of Dr. Robert M. Senior, Washington University School of Medicine at Barnes-Jewish Hospital
1996 - 1999 Research Instructor of Medicine, Division of Pulmonary and Critical Medicine, Washington University School of Medicine
1999 - present Assistant Professor of Medicine, Division of Pulmonary and Critical Medicine, Washington University School of Medicine
2001 - present Assistant Professor of Cell Biology and Physiology, Washington University School of Medicine

HONORS

Presidential Scholars Program - Southern Illinois Univ. at Edwardsville 1982 Ð 1986
Phi Beta Kappa - 1992
March of Dimes Predoctoral Fellowship recipient - 1992
American Lung Association, Research Training Fellowship 1994-1996
Parker B. Francis Fellowship, July 1996-1999
American Lung Association, Career Investigator Award, 2001-2004
LAM Foundation Established Investigator Award, 2002-2005

PUBLICATIONS

Miller, R.D., Hoffman, J.W., Powell, P.P., Kyle, J.W., Shipley, J.M., Bachinsky, D.R., and Sly, W.S. (1990) Cloning and characterization of the human b-glucuronidase gene. Genomics 7:280-283.
Shipley, J.M., Miller, R.D., Wu, B.M., Grubb, J.H., Christensen, S.G., Kyle, J.W., and Sly, W.S. (1991) Analysis of the 5Õ flanking region of the human b-glucuronidase gene. Genomics 10:1009-1018.
Shipley, J.M., Klinkerberg, M., Wu, B.M., Bachinsky, D.R., Grubb, J.H., and Sly, W.S. (1993) Mutational Analysis of a Patient with Mucopolysaccharidosis type VII and Identification of Pseudogenes. Am. J. Hum. Genet. 52:517-526.
Shipley, J.M., Grubb, J.H., and Sly, W.S. (1993) The Role of Glycosylation and Phosphorylation in the Expression of Active Human b-Glucuronidase. J. Biol. Chem. 268:12193-12198.
Baragi, V., Fliszar, C.J., Conroy, M.C., Ye, Q.-Z., Shipley, J.M., and Welgus, H.G. (1994) Contribution of the C-terminal Domain of Metalloproteinases to Binding by TIMP: C-terminal Truncated Stromelysin and Matrilysin Exhibit Equally Compromised Binding Affinities as Compared to Full-length Stromelysin. J. Biol. Chem. 269:12692-12697.
Belaaouaj, A., Shipley, J.M., Kobayashi, D.K., Popescu, N., Silverman, G., and Shapiro, S.D. (1995) Genomic organization, chromosomal location and tissue specific expression of human macrophage metalloelastase. J Biol Chem 270:14568-14575.
Shipley, J.M., Doyle, G.A.R., Fliszar, C.J., Ye, Q-Z., Johnson, L.L., Shapiro, S.D., Welgus, H.G., and Senior, R.M. (1996) The structural basis for the elastolytic activity of the 92 kDa and 72 kDa gelatinases: Role of the fibronectin type II-like repeats. J. Biol. Chem. 271:4335-4341.
Shipley, J.M., Wesselschmidt, R.L., Kobayashi, D.K., Ley, T.J., and Shapiro, S.D. (1996) Metalloelastase is required for macrophage mediated proteolysis and matrix invasion in mice. Proc. Natl. Acad. Sci. USA. 93:3942-3946.
Shipley, J.M., Shapiro, S.D., Rosenbloom, J., and Mecham, R.P. (1998) Latent TGF-b binding protein-2 is required for normal mouse development. Am. J. Respir. Crit. Care Med. 157:A246.
Vu, T.H., Shipley, J.M., Bergers, G., Berger, J.E., Helms, J.A., Hanahan, D., Shapiro, S.D., Senior, R.M., and Werb, Z. (1998) MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell. 93:411-422. 1998.
Liu, Z., Shipley, J.M., Vu, T.H., Zhou, X., Diaz, L.A., Werb, Z., and Senior, R.M.: Gelatinase B-deficient mice are resistant to experimental bullous pemphigoid. J. Exp. Med. 188, 475-482, 1998.
Betsayaku, T., Shipley, J.M., Liu, Z., and Senior, R.M. Gelatinase B does not protect against lipopolysaccharide-induced acute lung injury. Chest 116: 17S-18S, 1999.
Heymans, S., Luttun, A., Nuyens, D., Theilmeier, G., Creemers, E., Moons, L., Dyspersin, G.D., Cleutjens, J.P.M., Shipley, J.M., Angellilo, A., Levi, M., Nube, O., Baker, A., Keshet, E., Lupu, F., Herbert, J-M., Smits, J.F.M., Shapiro, S.D., Baes, M., Borgers, M., Collen, D., Daemen, M.J.A.P., and Carmeliet, P.: Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nature Medicine 5: 1135-1142, 1999.
Betsuyaku, T., Shipley, J.M., Liu, Z., and Senior, R.M.: Neutrophil emigration in the lungs, peritoneum, and skin does not require gelatinase B. Am. J. Respir. Cell Mol. Biol. 20:1303-1309, 1999.
Frankfater, C., Maus, E., Gaal, K., Segade, F., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., and Shipley, J.M. (1999) Organization of the mouse microfibril-associated glycoprotein-2 (MAGP-2) gene. Mammalian Genome 11:191-195, 2000.
Pyo, R., Lee, J.K., Shipley, J.M., Curci, J.A., Mao, D., Ziporin, S.J., Ennis, T.L., Shapiro, S.D., Senior, R.M. and Thompson, R.W.: Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms. J. Clin. Invest. 105:1641-1649, 2000.
Shipley, J.M., Mecham, R.P., Maus, E., Bonadio, J., Rosenbloom, J., McCarthy, R.T., Baumann, M.L., Frankfater, C., Segade, F., and Shapiro, S.D. Developmental expression of latent TGFb binding protein-2 (LTBP-2) and itÕs requirement early in mouse development. Mol. Cell. Biol. 20:4879-4887, 2000.
Andrews, K.L., Betsuyaku, T., Rogers, S., Shipley, J.M., Senior, R.M. and Miner, J.H.: Gelatinase B (MMP-9) is not essential in the normal kidney and does not influence progression of renal disease in a mouse model of Alport syndrome. Am. J. Pathol. 157:303-311, 2000.
Betsuyaku, T., Fukuda, Y., Parks, W.C., Shipley, J.M., and Senior, R.M.: Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin. Am. J. Pathol. 157:525-535, 2000.
Liu, Z., Zhou, X., Shapiro, S.D., Shipley, J.M., Twining, S.S., Diaz, L.A., Senior, R.M., and Werb, Z.: The serpin a1-proteinase inhibitor is the critical substrate for gelatinase B/MMP-9 in vivo. Cell 102:647-655, 2000.
Pierce, R.A. and Shipley, J.M. Retinoid-enhanced alveolization: Identifying relevant downstream targets. Am. J. Respir. Cell Mol. Biol. 23:137-141, 2000.
Lee, C.G., Homer, R.J., Zhu, H.Z, Lanone, S., Wang, X., Koteliansky, V., Shipley, J.M., Gotwals, P., Noble, P., Chen, Q., Senior, R.M., and Elias, J.A.: Interleukin-13 induces tissue fibrosis by selectively stimulating and activating TGF-b1. J. Exp. Med. 194:809-821, 2001.
Mohan, R., Chintala, S.K., Jung, J.C., Villar, W.v.L., McCabe, F., Russo, L.A., Lee, Y., McCarthy, B.E., Wollenberg, K.R., Jester, J.V., Wang, M., Welgus, H.G., Shipley, J.M., Senior, R.M., and Fini, M.E.: Matrix metalloproteinase Gelatinase B (MMP-9) coordinates and effects epithelial regeneration. J. Biol. Chem. 277:2065-2072, 2002.
Allport , J.R., Lim, Y.-C., Shipley, J.M., Senior, R.M., Shapiro, S.D., Matsuyoshi, N., Vestweber, D., and Luscinskas, F.W.: Neutrophil elastase or MMP-9 are not essential for murine neutrophil transendothelial migration in vitro. J. Leuk. Biol. In press, 2002.
Ratzinger, G., Stoitzner, P., Ebner, S., Lutz, M., Layton, GT, Rainer, C., Senior, RM., Shipley, JM, Fritsch, P., Schuler, G., and Romani, N.: Matrix metalloproteinases 9 and 2 are necessary for the migration of langerhans cells and dermal dendritic cells from human and murine skin. MMPs and migration of skin dendritic cells. J. Immunol. In press, 2002.

RESEARCH PROJECTS ONGOING OR COMPLETED DURING THE LAST 3 YEARS

"Role of Elastolytic Matrix Metalloproteinases in the Pathogenesis of Pulmonary Emphysema"
Agency: Parker B. Francis Foundation
Type: Parker B. Francis Fellowship Period: 07/01/96 Ð 06/30/99
The major goals of this project are to identify domains within the 92 kDa gelatinase and macrophage elastase which confer elastolytic activity, and to evaluate the role of these enzymes in a murine model of cigarette smoke induced emphysema through gene knockouts.
Role: Principal Investigator: J. Michael Shipley

"The Role of Microfibril-associated Glycoprotein-2 in Elastic Fiber Assembly"
Agency: Barnes-Jewish Hospital Foundation
Type: BJHF Grant Period: 01/01/99 Ð 12/31/00
The goals of this project are to clone the mouse MAGP-2 gene and generate knockout mice, to characterize both forms of MAGP-2 mRNA, to characterize the developmental expression of MAGP-2, and to identify regions of MAGP-2 and the fibrillin involved in the MAGP-2/fibrillin interaction.
Role: Principal Investigator: J. Michael Shipley

"LTBP-2: Structural and Regulatory Functions"
Agency: NIH, NHLBI HL60647
Type: RO1 Period: 8/7/98 Ð 7/31/03
The goals are to characterize LTBP-2 expression as it relates to TGF-b and elastic fibers, and to determine the basis for the embryonic lethal phenotype of the LTBP-2 knockout mouse.
Role: Principal Investigator: J. Michael Shipley

"Defining the Role of MAGP-2 in Microfibril Assembly"
Agency: NIH, NHLBI HL67353
Type: RO1 Period: 4/1/01 Ð 3/31/06
The goals of this project are to characterize the interaction between MAGP-2 and fibrillin and MAGP-1, the temporal and spatial expression of MAGP-2 in the developing mouse, and to generate and analyze MAGP-2 deficient mice.
Role: Principal Investigator: J. Michael Shipley

"Defining the role of MFAP-4 in microfibril assembly"
Agency: American Heart Association, Heartland Affiliate
Type: Beginning Grant-in-Aid Period: 7/1/2001 Ð 6/30/2003
The goals are to characterize the temporal and spatial expression of MFAP-4 in the developing mouse, generate and analyze MFAP-4 deficient mice, and identify other microfibrillar proteins that interact with MFAP-4.
Role: Principal Investigator: James Michael Shipley

"Generation of a mouse model of Lymphangioleiomyomatosis"
Agency: Barnes-Jewish Hospital
Type: BJHF Grant Period: 1/1/2002 Ð 12/31/2002
The goal of this study is to disrupt the function or expression of TSC2 in the adult mouse to mimic LAM, which would provide a vital reagent for future studies.
Role: Principal Investigator: J. Michael Shipley, Ph.D.

"Inducible Targeting of the TSC Genes in Adult Smooth Muscle"
Agency: The LAM Foundation
Type: Established Investigator Award Period: 1/15/2002 Ð 1/14/2005
The goal of this study is to disrupt the function or expression of TSC2 in the adult mouse to mimic LAM, which would provide a vital reagent for future studies.
Role: Principal Investigator: J. Michael Shipley

"Microfibril-associated glycoprotein-2 in elastogenesis"
Agency: American Lung Association
Type: Career Investigator Award Period: 7/1/2001 Ð 6/30/2004
The goals of this study are to characterize the MAGP-2/fibrillin interaction, the temporal and spatial expression of MAGP-2 in the developing mouse, and to generate and analyze MAGP-2 deficient mice.
Principal Investigator: J. Michael Shipley

Division of Pulmonary and Critical Care Medicine
Department of Medicine
Washington University School of Medicine