My laboratory focuses on understanding the regulation of stem cells during normal development, aging, and in cancer.
Recent identification of a special subset of cancer cells provides a new opportunity for meeting the challenge of eradicating human cancers, including glioblastomas, the most aggressive form of brain cancer that is currently incurable. Recent studies indicate that not all cancer cells are equal, and that only a small subset of cancer cells (called cancer stem cells) have the unique properties of being able to initiate cancer, divide infinitely, and give rise to all other cell types in the original cancer. These are necessary characteristics of cancer cells that spread from the original tumor to other sites (metastasis) and also those that instigate tumor recurrence. Consistent with the idea that cancer stem cells lie at the root of these major challenges in cancer treatment, recent studies show that cancer stem cells are more resistant than other cancer cells to radiation- and chemo-therapies. Hence, it is hypothesized that killing cancer stem cells will have a significant impact in treating cancer. However, pursuing such a strategy requires an understanding of the molecules that endow these cells with their unique properties, but the identity of these molecules is currently largely unknown.
To address this need, we take two complementary approaches. One, we are analyzing the functions of known oncogenes and tumor suppressor genes during development to understand their role in normal stem cell regulation. In particular, we are interested in genes that regulate self-renewal of stem cells since this is a common cellular process that is critical to all stem cells, including cancer stem cells. Two, we have identified 45 candidate genes that are unquely expressed in cancer stem cells, compared to non-stem cancer cells and normal stem cells. We are currently testing the expression and function of these genes in human and mouse brain and breast cancer cells. By combining these two approaches, we hope to gain valuable insightst that contributes to manipulating stem cells for cell-based therapies involving normal neural stem cells and in eradicating cancer.
- Yun K, Tennent B. (2008) Cancer stem cells. Drug Discov Today: Disease Models 4:47-52.
- Harris, MA, Yang, H, Low, BE, Mukherje J, Guha A, Bronson RT, Shultz, LD, Israel, MA, Yun, K, (2008) Cancer stem cells are enriched in the side-population cells in a mouse model of glioma, Cancer Research (2008).
- Nam JS, Park E, Turcotte TJ, Palencia S, Zhan X, Lee J, Yun K, Funk WD, Yoon JK. (2007) Mouse R-spondin2 is required for apical ectodermal ridge maintenance in the hindlimb. Dev Biol 311:124-135
- Yun, K., Mantani, A., Garel, S., Rubenstein, J., and Israel, M.A. (2004) Id4 regulates neural progenitor proliferation and differentiation in vivo. Development 131:5441-5448.
- Yun, K., Garel, S., Fischman, S., and Rubenstein, J.L. (2003) Patterning of the lateral ganglionic eminence by the Gsh1 and Gsh2 homeobox genes regulates striatal and olfactory bulb histogenesis and the growth of axons through the basal ganglia. The Journal of Comparative Neurology 461:151-165.
- Andrews, G.L., Yun, K., Rubenstein, J.L., and Mastick, G.S. (2003) Dlx transcription factors regulate differentiation of dopaminergic neurons of the ventral thalamus. Molecular and Cellular Neurosciences 23:107-120.
- Yun, K., Fischman, S., Johnson, J., Hrabe de Angelis, M., Weinmaster, G., and Rubenstein, J.L. (2002) Modulation of the Notch signaling by Mash1 and Dlx1/2 regulates sequential specification and differentiation of progenitor cell types in the subcortical telencephalon. Development 129:5029-5040.
- Garel, S., Yun, K., Grosschedl, R., and Rubenstein, J.L. (2002) The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice. Development 129:5621-5634.
- Yun, K., Potter, S., and Rubenstein, J.L. (2001) Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon. Development 128:193-205.
- Anderson, S., Mione, M., Yun, K., and Rubenstein, J.L. (1999) Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis. Cereb Cortex 9:646-654.
- Yun, K., and Wold, B. (1996) Skeletal muscle determination and differentiation: story of a core regulatory network and its context. Current Opinion in Cell Biology 8:877-889.
GRANT REVIEW/STUDY SECTIONS
NCI, Review Committee for RFA: “Tumor Stem Cells in Cancer Biology,
Prevention, and Therapy (P01),” Nov 2008
INSTITUTIONAL COMMITTEES (The Jackson Laboratory)
Animal Care and Usage committee
Cancer Center Advisory committee
Human Subjects IRB
Institutional Biosafety Committee
Graduate Program Advisory committee
Senior Cancer Researcher Search Committee