Jung-whan (Jay) Kim, DVM, PhD
Assistant Professor Molecular & Cell Biology
DVM, Konkuk University, Korea – Veterinary Medicine
PhD, Johns Hopkins Medical School – Cancer Metabolism and Hypoxia
Postdoctoral Training, UCSD (Randall Johnson Lab) / Salk Institute (Reuben Shaw Lab)
Our research group is focused on understanding the role of hypoxic response in the regulation of tumor microenvironmental remodeling and metabolic reprograming in cancers. Another major focus of our research is to understand the role of stromal cells including fibroblasts, adipocytes and inflammatory cells in cancer progression.
Stromal Fibroblasts within the Tumor Microenvironment
Tumor-associated stromal alterations are integral components of the tumor microenvironment that contribute to tumor growth and progression. Among many cellular populations, stromal fibroblasts are prominent cell populations of the tumor microenvironment and have been implicated in the development of various cancers including breast and pancreatic cancers. my laboratory is interested in the mechanisms underlying the effects of stromal hypoxic signaling in tumorigenesis, angiogenesis and remodeling of the tumor microenvironment. The remodeling response to hypoxia is controlled primarily by hypoxia-inducible transcription factors (HIFs). We employ transgenic animal models in which the hypoxic response has been genetically ablated via deletion of HIFs in various stromal components including fibroblasts in various tumor models to better understand the relationship of tumor-associated stromal cells to tumor progression in the context of the hypoxic tumor microenvironment.
Adipocyte hypoxic response in mammary tumor progression
Mammary gland is a unique organ that is embedded in connective tissue composed mainly of adipocytes. Dynamic mammary epithelial cell/adipocyte interaction is an essential component of normal mammary gland homeostasis. In the context of mammary tumor progression, however, tumor-associated adipocytes promote tumor cell proliferation, invasion, and metastatic progression. Obesity correlates with poor prognosis and aggressiveness of breast cancer, suggesting that disrupted adipose tissue homeostasis exacerbates malignancy, but the mechanisms of adipocyte-mediate increases in mammary tumor progression are largely unknown. Adipose tissue in obesity is hypoxic due to adipocyte hypertrophy and hyperplasia, which leads to insufficient blood perfusion suggesting that HIF signaling is critical in obese adipose tissue remodeling and may play a pivotal role in mammary tumor microenvironment
We are currently utilizing adipocyte specific HIFs-null mice in conjunction with the PyMT mammary tumor model or orthotropic mammary tumor model to (i) determine the mechanisms of adipocyte/tumor cell interaction; (ii) investigate mechanisms of adipocyte-mediated pro-tumorigenic action; and (iii) explore the link between obesity and breast cancer risk and progression.
Role of HIFs in Non-Small Cell Lung Cancers
Recent studies have shown that HIF-1α signaling is significantly elevated in LKB1-deficient lung cancers. Utilizing a panel of human non-small cell lung cancer cell lines and mouse model of human lung cancer with lung specific recombination of oncogenic Kras and deletion of LKB1 and HIFs, which lead to spontaneous lung cancer formation in these mice, we are seeking to address whether the activation of HIF-1 or HIF-2 signaling in the LKB1-deficient non-small cell lung cancer plays a critical pro-tumorigenic role.
- Jonathan Chou, Jeffrey Lin, Audrey Brenot, Jung-whan Kim, Sylvain Provot and Zena Werb. GATA3 Suppresses Metastasis and Modulates the Tumor Microenvironment by Regulating miR-29b Expression. Nature Cell Biology, 15:201-213(2013)
- Jung-whan Kim, Colin Evans, Alexander Weidemann, Norihiko Takeda, Yun Sok Lee, Christian Stockmann, Cristina Branco-Price, Filip Branberg, Gustavo Leone, Michael Ostrowski and Randall Johnson. Loss of Fibroblast HIF-1a Accelerates Tumorigenesis. Cancer Research, 72:3187-95 (2012)
- Norihiko Takeda, Ellen L. O’Dea, Andrew Doedens, Jung-whan Kim, Alexander Weidemann, Christian Stockmann, Masataka Asagiri, M. Selete Simon, Alexander Hoffmann and Randall S. Johnson. Differential activation and antagonistic function of HIF-a isoforms in macrophages are essential for NO homeostasis. Genes and Development 24:491-501 (2010)
- Jung-whan Kim, Ping Gao, Yen-Chun Liu, Gregg L. Semenza and Chi V. Dang. HIF-1 and dysregulated c-Myc cooperatively induce VEGF and metabolic switches, HK2 and PDK1. Mol. Cell. Biol. 27:7381-7393 (2007)
- Ryo Fukuda, Huafeng Zhang, Jung-whan Kim, Larissa Shimoda, Chi V. Dang, and Gregg L. Semenza. HIF-1 regulates cytochrome oxidase subunit composition to optimize the efficiency of respiration of hypoxic cells. Cell 129:111-122 (2007)
- Jung-whan Kim, Irina Tchernyshyov, Gregg L. Semenza, and Chi V. Dang. HIF-1-mediated expression of PDK: a metabolic switch required for cellular adaptation to hypoxia. Cell Metabolism, 3:177-185 (2006) *Featured Cover Article (Mar 2006)
- Feng Li, Diane Wonsey, Young Ko, Kathryn O’Donnell, Karen Zeller, Jung-whan Kim, Jason Yustein, Linda Lee and Chi Dang. Myc stimulates mitochondrial biogenesis and nuclear encoded mitochondrial genes, Mol. Cell. Biol. 25: 6225-6234 (2005)
- Jung-whan Kim, Karen I. Zeller, Yunyue Wang, Anil G. Jegga, Bruce J. Aronow, Kathryn A. O’Donnell, and Chi V. Dang. Evaluation of Myc E-Box Phylogenetic Footprints in Glycolytic Genes by Chromatin Immunoprecipitation Assays. Mol. Cell. Biol. 24:5923-5936 (2004)
- Updated: April 16, 2013