Jong-In Park, Ph.D.

Assistant 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 using yeast as a model organism.  He was a postdoctoral fellow at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins from 2000 to 2005 where he investigated tumor suppressive mechanisms activated upon Ras/Raf activation.  Dr. Park joined the faculty of the Biochemistry Department at the Medical College of Wisconsin in 2006.

Contact Information

jipark@mcw.edu
Phone: (414) 456-4098
Fax: (414) 456-6510

Research Interests

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

The Ras and Raf families of oncogenes have been known for decades as transforming genes, and activation of the Ras/Raf/MEK/ERK pathway is a central feature of many epithelial cancers.  However, aberrant activation of Ras or its downstream effector Raf rather elicits cell cycle arrest and senescence in primary cultured normal cells, suggesting that this response is a primary defense against the Ras/Raf-induced oncogenesis.  Indeed, a number of in vivo data support this theory, as demonstrated during progression of melanoma, and in mouse models of lymphoma, lung adenocarcinoma and pancreatic cancer.  However, molecular mechanisms underlying the contradicting Ras/Raf signaling are yet unclear.

Interestingly, the terminal growth arrest response to Ras/Raf/MEK/ERK activation has also been observed in many tumor cell lines, suggesting that these types of tumor cells may still possess the natural defense systems against aberrant Ras/Raf activation.  Finding a way to mobilize the defense systems in these tumors may aid in designing novel therapeutic strategies.

Our overall goal is to understand the mechanistic difference of Ras/Raf-induced growth inhibition vs. proliferation at molecular levels.  Our research focuses on elucidating signaling networks specifically involved in Ras/Raf-induced growth inhibition, including cell-intrinsic as well as cell-extrinsic pathways.  We previously identified leukemia inhibitory factor (LIF) as an autocrine/paracrine factor that can mediate the cell-extrinsic growth inhibition of Ras/Raf.  We continue our effort on investigating the signaling pathways regulated by LIF in the context of Ras/Raf-induced tumor suppression.  Currently, we are analyzing molecular mechanisms of IFI16 upregulation and E2F1 downregulation at transcriptional and translational levels, which are essential for LIF-mediated growth inhibition.  Our effort also includes identification of additional soluble factors involved in the cell-extrinsic growth inhibitory signaling of Ras/Raf using techniques in protein purification and proteomics, and analysis of growth inhibition-specific signaling mechanisms of the MEK/ERK cascade using a variety of biochemical, molecular biological, and cell biological approaches.  

Selected Publications

"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-cAMP Signal Transduction Pathway."  J.-I. Park, C. M. Grant, P. V. Attfield, and I. W. Dawes. Applied and Environmental Microbiology, 63: 3818-3824 (1997)