Jong-In Park, PhD
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 studied cancer biology. Dr. Park joined the faculty of the Biochemistry Department at the Medical College of Wisconsin in 2006.
Dr. Park’s research on cancer is currently supported by NIH-National Cancer Institute and the American Cancer Society (ACS). Dr. Park is currently an ACS Research Scholar and a member of the ACS MEN2 Thyroid Cancer Consortium. Dr. Park also participates in the NCI-MATCH trial as the Translational Chair of the Dabrafenib & Trametinib combination therapy arm, which targets BRAF-driven cancer.
Phone: (414) 955-4098
Fax: (414) 955-6510
Proliferative programs of normal mammalian cells are interfaced with a variety of innate tumor-suppressive mechanisms that can trigger growth arrest or cell death in response to aberrant cell proliferation signals. Therefore, for carcinogenesis to occur, these mechanisms must be inactivated (A model is depicted at right).
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 different types of tumor cells in which the pathway signaling is not aberrant, suggesting that certain tumor types still possess the natural defense systems against aberrant activation of the pathway. The overall goal of our research is to understand the mechanisms by which 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 current 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. Investigating the role of mortalin/GRP75/HSPA9 for Raf/MEK/ERK-mediated growth inhibition. We recently demonstrated, using a tandem affinity purification procedure to identify proteins interacting with MEK or ERK, that mortalin is a negative regulator of Raf/MEK/ERK acting at MEK level. We also demonstrated that targeting mortalin in Raf/MEK/ERK-activated cancer can reactivate the pathway-mediated tumor suppressive signaling. Current study focuses on identifying the molecular mechanisms by which mortalin regulates Raf/MEK/ERK signaling.
3. Investigating Raf/MEK/ERK-mediated tumor suppressive signaling in thyroid cancer. 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. We recently demonstrated that recombinant LIF has therapeutic efficacy in human tumor xenograft models in mice. Current focus is on evaluating therapeutic potential of LIF in combination with other therapeutic agents. Further, we study the potential of targeting mitochondrial metabolism in designing a therapeutic strategy for thyroid cancer.