Jong-In Park, Ph.D.

Associate Professor

Dr. Park received his Bachelor’s and Master’s degrees in Biochemistry from Yonsei University, Seoul, Korea, and his Doctorate degree in Biochemistry and Molecular Genetics from the University of New South Wales, Sydney, Australia. The latter was awarded in 2000 for studies in Ras pathway-mediated stress responses. He was a postdoctoral fellow at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University from 2000 to 2005 where he investigated tumor suppressive mechanisms activated by aberrant Ras/Raf/MEK/ERK signaling. Dr. Park joined the faculty of the Biochemistry Department at the Medical College of Wisconsin in 2006. Dr. Park’s research is currently supported by NIH-National Cancer Institute. Dr. Park is also a Research Scholar of American Cancer Society and a Young Clinical Scientist of Flight Attendant Medical Research Institute.

Contact Information

Phone: (414) 955-4098
Fax: (414) 955-6510
Email: jipark@mcw.edu

Research Interests

Proliferative programs of normal mammalian cells are interfaced with a variety of innate tumor-suppressive mechanisms that can trigger cell death or senescence in response to aberrant cell proliferation. Therefore, for carcinogenesis to occur, these defensive mechanisms must be inactivated. 

The Ras and Raf families of oncogenes have been known for decades as transforming genes, and activation of the Raf/MEK/ERK pathway (the MAP kinase cascade of Ras) is a central signature of many epithelial cancers. However, paradoxically, aberrant activation of Ras or Raf elicits growth inhibitory effects, mainly characterized by cell cycle arrest and senescence, in primary cultured normal cells and in vivo. These responses are now appreciated as cellular innate defense mechanisms against Ras- and Raf-mediated tumorigenesis. Interestingly, the growth inhibitory effects of Ras/Raf/MEK/ERK activation are also observed in certain tumor cell lines in which the pathway signaling is not aberrant, suggesting that certain tumor cell types still possess the natural defense systems against aberrant activation of the pathway. Our overall goal is to understand by what mechanisms the Ras/Raf/MEK/ERK pathway mediates tumor suppressive signaling and to find a way to control the signaling, which may aid in designing novel therapeutic strategies.

Our research focuses include:

1. Investigating functional mechanisms of ERK required for mediating growth inhibition. We recently demonstrated, using molecular and cellular biological approaches, that ERK1/2 has a biochemical function other than its canonical kinase activity, which is utilized to mediate the Raf/MEK/ERK pathway-induced growth arrest. Current study focuses on identifying the mechanisms underlying this novel ERK signaling.

2. Identifying growth arrest specific regulators of MEK/ERK. We have developed a tandem affinity purification procedure to identify proteins interacting with MEK or ERK. Current study focuses on identifying MEK/ERK interacting proteins using this method and evaluating their involvement in the pathway-mediated growth inhibitory signaling.

3. Identifying cell-extrinsic growth inhibitory pathways of Ras/Raf/MEK/ERK. We previously identified, using column chromatography and proteomic mass spectrometry, leukemia inhibitory factor (LIF) as an autocrine/paracrine factor that can mediate cell-extrinsic growth inhibitory signaling of Ras/Raf/MEK/ERK in certain cancer types including medullary thyroid cancer and pheochromocytoma. Current focus is on evaluating therapeutic potential of LIF and identifying additional factors with therapeutic potential.  

Selected Publications

“The Raf/MEK/extracellular signal-regulated kinase ½ pathway can mediate growth inhibitory and differentiation signaling via androgen receptor downregulation in prostate cancer cells.” S. Hong, J. Kim, M. Lin, J.-I. Park, Experimental Cell Research, In Press (2011)

“Cooperative cross-talk between neuroblastoma subtypes confers resistance to Anaplastic Lymphoma Kinase inhibition.” X. Yan, C. Kennedy, S. Tilkens, O. Wiedemeier, H. Guan, J.-I. Park, A. Chan, Genes & Cancer, In Press (2011)

"Leukemia inhibitory factor can mediate Ras/Raf/MEK/ERK-induced growth inhibitory signaling in medullary thyroid cancer cells." D. Arthan, S. Hong, J.-I., Park. Cancer Letters In Press ( doi:10.1016/j.canlet.2010.04.021)

"Non-Catalytic Function of Extracellular Signal-Regulated Kinase ½ (ERK1/2) Can Promote Raf/MEK/ERK-Mediated Growth Arrest Signaling." S. Hong, S. Yoon, C. Moelling, D. Arthan, J.-I. Park. Journal of Biological Chemistry, 284: 33006-33018 (2009)

"Oxidative Stress Inhibits IGF-I Induction of Chondrocyte Proteoglycan Synthesis through Differential Regulation of PI-3 Kinase-Akt and MEK-ERK MAPK Signaling Pathways." W. Yin, J.-I. Park, R. Loeser. Journal of Biological Chemistry, 284: 31972-31981 (2009)

"Cyclin-Dependent Kinase 5 Activity Controls Cell Motility and Metastatic Potential of Prostate Cancer Cells." C. J. Strock, J.-I. Park, E. K. Nakakura, G. S. Bova, J. T. Isaacs, D. W. Ball, B. D. Nelkin. Cancer Research, 66: 7509-7515 (2006)

"Activity of Irinotecan and the Tyrosine Kinase Inhibitor CEP-751 in Medullary Thyroid Cancer." C. J. Strock, J.-I. Park, D. M. Rosen, B. Ruggeri, S. R. Denmeade, D. W. Ball, and B. D. Nelkin. Journal of Clinical Endocrinology and Metabolism, 91: 79-84 (2006)

"IFI16 Is an Essential Mediator of Growth Inhibition, but not Differentiation, Induced by the Leukemia Inhibitory Factor/JAK/STAT Pathway in Medullary Thyroid Carcinoma Cells." E.-J. Kim, J.-I. Park, and B. D. Nelkin. Journal of Biological Chemistry, 280: 4913-4920 (2005)

"Interleukin-1β Can Mediate Growth Arrest and Differentiation via the Leukemia Inhibitory Factor/JAK/STAT Pathway in Medullary Thyroid Carcinoma Cells." J.-I. Park, C. J. Strock, D. W. Ball, and B. D. Nelkin. Cytokine, 29: 125-134 (2005)

"GDNF-Induced Leukemia Inhibitory Factor Can Mediate Differentiation via the MEK/ERK Pathway in Pheochromocytoma Cells Derived from nf1 Knockout Mice." J.-I. Park, J. F. Powers, A. S. Tischler, C. J. Strock, D. W. Ball, and B. D. Nelkin. Experimental Cell Research, 303: 79-88 (2005)

"Rom2p, the Rho1 GTP/GDP Exchange Factor of Saccharomyces cerevisiae, Can Mediate Stress Responses via the Ras-cAMP Pathway." J.-I. Park, E. J. Collinson, C. M. Grant, and I. W. Dawes. Journal of Biological Chemistry, 280: 2529-2535 (2005)

"The High-affinity cAMP Phosphodiesterase of Saccharomyces cerevisiae Is the Major Determinant of cAMP Levels in Stationary Phase: Involvement of Different Branches of the Ras-cyclic AMP Pathway in Stress Responses." J.-I. Park, C. M. Grant, and I. W. Dawes. Biochemical and Biophysical Research Communications, 327: 311-319 (2005)

"Regulation and Function of Trefoil Factor Family 3 Expression in the Biliary Tree." I. Nozaki, J. G. Lunz 3rd, S. Specht, J.-I. Park, A. S. Giraud, N. Murase, and A. J. Demetris. American Journal of Pathology, 165: 1907-1920 (2004)

"CEP-701 and CEP-751 Inhibit Constitutively Activated RET Tyrosine Kinase Activity and Block Medullary Thyroid Carcinoma Cell Growth."  C. J. Strock, J.-I. Park, M. Rosen, C. Dionne, B. Ruggeri, S. Jones-Bolin, S. R. Denmeade, D. W. Ball, and B. D. Nelkin. Cancer Research, 63: 5559-5563 (2003)

"Epidermal Growth Factor Receptor-independent Constitutive Activation of STAT3 in Head and Neck Squamous Cell Carcinoma Is Mediated by the Autocrine/Paracrine Stimulation of the Interleukin 6/gp130 Cytokine System." V. Sriuranpong, J.-I. Park, P. Amornphimoltham, V. Patel, B. D. Nelkin, and J. S. Gutkind. Cancer Research, 63: 2948-2956 (2003)

"The Ras/Raf/MEK/ERK Pathway Induces Autocrine/Paracrine Growth Inhibition via the Leukemia Inhibitory Factor/JAK/STAT Pathway."  J.-I. Park, C. J. Strock, D. W. Ball, and B. D. Nelkin. Molecular and Cellular Biology, 23: 543-554 (2003)

"The Cytoplasmic Cu,Zn Superoxide Dismutase of Saccharomyces cerevisiae Is Required for Resistance to Freeze-Thaw Stress." J.-I. Park, C. M. Grant, M. J. Davis, and I. W. Dawes. Journal of Biological Chemistry, 273: 22921-22928 (1998)

"The Freeze-Thaw Stress Response of the Yeast Saccharomyces cerevisiae Is Growth-Phase Specific and Controlled by Nutritional State via the RAS-cyclic AMP Signal Transduction Pathway."  J.-I. Park, C. M. Grant, P. V. Attfield, and I. W. Dawes. Applied and Environmental Microbiology, 63: 3818-3824 (1997)