School of Medicine

Wayne State University School of Medicine

Profile

Hyeong-Reh Kim, Ph.D.
Professor
Department of Pathology
Scott Hall, Room 9271
540 East Canfield Avenue
Detroit, MI 48201
313-577-2407
Areas
Growth factor signaling, extracelluar matrix signaling, metastasis, tumor-stromal interactions, and apoptosis
Research Interests

The long term objective of Dr. Kimís research is to unveil the molecular and cellular mechanisms by which proteolytic and growth factor signaling networks contribute to tumor progression.  Dr. Kimís laboratory has investigated platelet-derived growth factor (PDGF) isoform-specific signal transduction pathways and their roles in prostate and breast cancer progression.   Recently, Dr. Kimís laboratory showed that tumor-produced PDGF C and D undergo proteolytic activation by the serine proteases uPA and matriptase and mediate stromal reactions, critical for tumor cell invasion and metastasis.  The laboratory of Dr. Kim has also investigated the pleiotropic activity of tissue inhibitor of metalloproteinases (TIMP)-1 during cancer progression.  Dr. Kimís recent study identified the tetraspanin member CD63 as the first TIMP-1 binding cell surface protein, which mediates the integrin β1 survival pathway as well as phenotypic changes resembling an epithelial mesenchymal transition (EMT).
 

Education

Ph.D. (1989): Northwestern University, Evanston, IL, USA

Postdoctoral Fellowship

1990-1991, Northwestern University Cancer Center, Chicago, IL, USA
1991-1992, Washington University, St. Louis, MO, USA
 

Publications

1.† Yu, J-H., Deuel, T., and Kim, H-R. C.† Platelet-derived growth factor (PDGF) receptor-alpha activates JNK-1 and antagonizes PDGF receptor-beta-induced phenotypic transformation. J. Biol. Chem. 275: 19076-19882, 2000.†

2.† Liu, X-W, Bernardo, M.M., Fridman, R. and Kim, H.-R. C.† Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Protects Human Breast Epithelial Cells against Intrinsic Apoptotic Cell Death via the FAK/PI 3-kinase and MAPK Signaling Pathway Independent of Matrix Metalloproteinase Inhibition. †J. Biol. Chem. 278: 40364-40372, 2003††

3.† Yu, J. Liu, X-W, and† Kim, H.-R. C.† Platelet-Derived Growth Factor (PDGF) Receptor-alpha-activated c-Jun NH2-terminal Kinase-1 is critical for PDGF-induced p21WAF1/CIP1 promoter activity independent of p53.† †J. Biol. Chem. 278: 49582-49588, 2003

4.† Ustach, C. V., Taube, M. E.,† Hurst, N., Bagat, S., Bonfil, D., Cher, M., Schuger, L and Kim, H.-R. C.† A†potential oncogenic activity of PDGF D in prostate cancer progression.† Cancer Research, 64: 1722-1729, 2004† † † ††

5.† Liu, X-W., Taube, M.E., Jung, K-K., Zhong, D.,Lee, Y. J., Roshy, S., Sloane, S., Fridman, R and Kim, H.-R. C. Tissue Inhibitor of Metalloproteinase-1 protects human breast epithelial cells from extrinsic cell death:† A potential oncogenic activity of TIMP-1.† Cancer Research, 65: 898-906, 2005

6.† Ustach C. and Kim, H.-R. C.† Platelet-Derived Growth Factor D is activated by Urokinase Plasminogen Activator in Prostate Carcinoma Cells.† Mol. Cell. Biol ,25(14):6279-6288, 2005

7. †Taube, M.E., Liu, X-W, Fridman, R. and Kim, H.-R. C. TIMP-1 regulation of cell cycle in human breast epithelial cells via stabilization of p27KIP1 protein.† Oncogene 25: 3041-3048, 2006

8.† Jung, K-K., Liu, X-W., Chirco, R., Fridman, R., and Kim, H.-R. C.† Identification of CD63 as a Tissue Inhibitor of Metalloproteinase-1† interacting cell surface protein.† The EMBO J., 25:3934-3942, 2006

9.† Ustach, C.V., Huang, W., Conley-LaComb, M.K., Lin, C-Y., Che, M., Abrams, J. and Kim, H.-R. C. †A novel signaling axis of matriptase/PDGF D/?-PDGFR in human prostate cancer. Cancer Research, 70: 9631-40, 2010

10. Hurst, N.J., Najy, A., Ustach, C.V., Movilla, L., Huang, W., and Kim, H.-R. C.† Platelet-derived growth factor-C (PDGF-C) activation by serine proteases:† Implications for breast cancer progression.† Biochemical J.† 441: 909-918, 2012

11. Huang, W., Fridman, Y., Bonfil, R.D., Ustach, C.V., Conley-LaComb1,M.K., Wiesner, C., Saliganan, A., Cher, M.L., and Kim, H.-R. C. A novel function for platelet-derived growth factor D:† Induction of osteoclastogenesis for intraosseous tumor growth.† Oncogene, In press, 2012

12. Conley-LaComb, M.K., Huang, W., Wang, S., Shi, D., Jung, Y.S., Najy, A., Fridman, R., Bonfil, R.D., Cher, M., Chen, Y.Q., and Kim, H.-R. C.† PTEN regulates PDGF ligand switch for beta-PDGFR signaling in prostate cancer.† Am. J. Pathology, 180: 1017-1027, 2012

13. Jung, Y.S, Liu, X-W., Chirco, R., Warner, R.B., Rafael Fridman, R. and Kim, H.-R. C. TIMP-1 induces an EMT-like phenotypic conversion in MDCK cells independent of its MMP-inhibitory domain.† PLoS One, 7(6):e38773, 2012

14. Najy, A., Won, J.J., Lisa S. Movilla, L.S., and Kim, H.-R. C.† Differential Tumorigenic Potential and Matriptase Activation between PDGF B vs. PDGF D in Prostate Cancer.† Mol Cancer Research 10(8):1087,97, 2012