Johns Hopkins University, Ph.D.
Seoul National University, M.D.
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The ultimate goal of biomedicine is to help people live longer and healthier. Preventing death and repairing the aged/diseased organs are essential to achieve this goal. Cancer is the most common cause of death, and organ failure is the most common feature of aging-related diseases. Therefore, regenerative medicine and cancer precision medicine are key areas of convergence biomedical research to prolong human life in the era of 4th industrial revolution.
Our mission is to make innovative and ground-breaking, convergence stem cell and cancer research and translate our research discoveries for the improvement of health and the cure of diseases. The core values of our research group include highest level of professionalism, creativity, innovation, integrity, motivation, resilience, mutual care and team-work. With this mission and core values in mind, we study these three inter-connected and synergizing research areas of (1) stem cell biology & regenerative medicine, (2) cancer biology & precision medicine, (3) aging & anti-aging medicine.
Stem cells and cancers are tightly inter-related. Stem cells are oftentimes are the cell of origin for cancers. Also cancers have a subpopulation of cells, so called cancer stem cells (CSCs, a.k.a. tumor-initiating cells), which have stem cell-like characteristics and are considered the source of cancer recurrence. On the other hand, cancer is one of major aging diseases, and stem cells and stem-cell derived organs are the potential sources for anti-aging medicine. Therefore, stem cell research and cancer research are cross-connected and mutually applicable.
Our detailed research focuses include, but are not limited to,
I. Identification of tissue stem cells and their self-renewal mechanisms
– Still many tissue stem cells have not been identified. Furthermore, stem cell self-renewal and expansion are invaluable for regenerative medicine. We have extensive experience and expertise in these areas and will continue to achieve original and more significant research findings to identify and expand stem cells for regenerative medicine.
– The ultimate goal of stem cell biology and regenerative medicine is to generate micro-, mini-, and macro-organ to be used for organ transplantation. Although some researchers including our group succeeded in generating epithelial organoids and some of micro-organs derived from ESCs or iPSCs, the destination is still far to reach. We have built up strong experiences and expertise in epithelial stem cell biology and gear up toward organogenesis.
III. Development of targeted therapies for cancers
– Individualized precision medicine will ultimately refine and maximize the cancer treatment effect and minimize the side effects. We have shown that mutations in Keap1-Nrf2 anti-oxidant pathway promote the pathogenesis of lung squamous cell carcinoma by deregulating airway stem cell self-renewal. We further demonstrated that KEAP1/NRF2 mutations confer lung cancers therapeutic resistance and that genetic pre-screening of the mutation status of lung cancers could help us predict cancer recurrence. Now we aim to develop novel therapies precisely targeting KEAP1/NRF2 mutant cancers and cancers with other mutations.
IV. Targeting cancer stem cells (CSCs)
You have to remove the root if you want to get rid of weeds. Likewise, CSC theory suggests that we need to eliminate CSCs to cure cancers. CSCs are a subpopulation of cancer cells with the stem cell-like characteristics and are more resistant to chemotherapy and radiation therapy. We are particularly interested in identifying and targeting CSCs in head and neck and lung cancers.
V. Stem cell therapy in lung fibrosis
Idiopathic pulmonary fibrosis (IPF) is one of the representative aging diseases. IPF is a progressive, restrictive lung disease. In IPF, lung epithelium becomes thickened and scarred, impairing gas exchange. However, the role of lung stem cells and their niche in IPF pathogenesis has not been well understood. Thus, we aim to further elucidate the role of lung stem cells in IPF pathogenesis and treatment.
- Jeong Y, Hoang NT, Lovejoy A, Stehr H, Newman AM, Gentles AJ, Kong W, Truong D, Martin S, Chaudhuri A, Heiser D, Zhou L, Say C, Carter JN, Hiniker SM, Loo BW Jr, West RB, Beachy P, Alizadeh AA, Diehn M. Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance. Cancer Discov. 2017 Jan;7(1):86-101. doi: 10.1158/2159-8290. PMID: 27663899
- Jeong Y, Rhee H, Martin S, Klass D, Lin Y, Nguyen le XT, Feng W, Diehn M. Identification and genetic manipulation of human and mouse oesophageal stem cells. Gut. 2016 Jul;65(7):1077-86. doi: 10.1136/gutjnl-2014-308491. PMID: 25897018
- Jeong Y, Swami S, Krishnan AV, Williams JD, Martin S, Horst RL, Albertelli MA, Feldman BJ, Feldman D, Diehn M. Inhibition of Mouse Breast Tumor-Initiating Cells by Calcitriol and Dietary Vitamin D. Mol Cancer Ther. 2015 Aug;14(8):1951-61. doi: 10.1158/1535-7163.MCT-15-0066. PMID: 25934710
- Zhou B, Damrauer JS, Bailey ST, Hadzic T, Jeong Y, Clark K, Fan C, Murphy L, Lee CY, Troester MA, Miller CR, Jin J, Darr D, Perou CM, Levine RL, Diehn M, Kim WY. Erythropoietin promotes breast tumorigenesis through tumor-initiating cell self-renewal. J Clin Invest. 2014 Feb;124(2):553-63. doi: 10.1172/JCI69804. PMID: 24435044
- Jeong Y, Chaupin DF, Matsushita K, Yamakuchi M, Cameron SJ, Morrell CN, Lowenstein CJ. Aldosterone activates endothelial exocytosis. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3782-7. doi: 10.1073/pnas.0804037106. Epub 2009 Feb 17. PMID: 19223584