Jayoung Kim, Ph.D.
Staff Scientist, Children's Hospital Boston
Instructor, Harvard Medical School

John F. Enders Research Laboratories
Room 1152
300 Longwood Avenue
Boston, MA 02115
617-919-2639 (office)
617-730-0238 (fax)
ja.kim@childrens.harvard.edu

I joined the Freeman Lab in May, 2000. My research goal is to evaluate the mechanism of urological disease including prostate cancer. I was trained as a cell biologist during my Ph.D. studies, when I focused on signaling through the PI3-kinase/PKB/Akt pathway, and on crosstalk with other pathways such as Erk/MAPK and p38 MAPK. This training helped to establish my current interests in cellular signaling and resulted in publications in the Journal of Biological Chemistry, Archives of Biochemistry and Biophysics, and Biochemical and Biophysical Research Communications.

I recently made the observation that heparin-binding EGF-like growth factor (HB-EGF), an EGF receptor activating protein studied extensively in the Freeman Lab, is capable of stimulating neuroendocrine differentiation of LNCaP prostate cancer cells. I studied the molecular basis for this effect and was able to show that the mechanism was quite different than previously-described signaling pathways controlling this phenomenon--largely studies in which IL-6 was used as the differentiation agonist. I was able to demonstrate that, although neuroendocrine differentiation can be elicited by this growth factor, this phenotypic change does not necessarily require withdrawal from the cell cycle as previously thought. Neuroendocrine-like cancer cells are typically aggressive. Consequently, although my experiments were all in vitro, they are consistent with pre-existing clinical literature. They also suggest that the prostatic stroma, where HB-EGF is synthesized, might be able to promote tumor progression via a paracrine mechanism. These studies were published in Cancer Research, 2002. A separate paper, in which some of the ideas originating from my HB-EGF study were tested and validated in an in vivo model, is published in Endocrinology, 2002. In addition to these studies, I undertook and completed a third study. This involved the first demonstration that differentiation effects of doxorubicin are mediated in human breast cancer cells by the JNK/SAPK pathway. A manuscript describing these findings was published this year (2003) in Breast Cancer Research and Treatment. Recently, I have been testing the hypothesis that signal transduction through lipid raft microdomains plays an important role in cell survival signaling and tumor progression in prostate cancer. In 2003 I received a Research Scholar Fellowship from the American Foundation for Urological Disease on this topic.

Honors, Awards, and Service

Selected Publications

Kim, J., Jahng, W.J., Vizio, D.D., Lee, J., Rubin, M.A., Shisheva, A., and Freeman, M.R. (2007) The phosphoinositide kinase PIKfyve is a mediator of the nuclear EGF receptor transcription function. Cancer Research (In press).

Kim, J., Keay, S.K., Dimitrakov, J.D., and Freeman, M.R. (2007) p53 modulates the interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of urothelial cells. FEBS letters (In press).

Adam, R.M., Mukhopadhyay, N.K., Kim, J. Di Vizio, D., Cinar, B., Boucher, K., Solomon, K.R., and Freeman, M.R. (2007) Cholesterol sensitivity of endogenous and myristoylated Akt. Cancer Research 67(13):6238-6246.

Mukhopadhyay, N.K., Cinar, B., Mukhopadhyay, L., Lutchman M., Ferdinand, A.S., Kim, J., Chung L.W.K., Adam, R.M., Ray S.K., Leiter A.B., Richie, J.P., Liu, B.C.S., Freeman M.R. (2007) The zinc finger protein RREB-1 is a co-regulator of the androgen receptor: implication s for the role of the Ras pathway in enhancing androgenic signaling in prostate cancer. Molecular Endocrinology Epub ahead of print, Jun 5.

Park, Y.S., Kim, J., Misonou, Y, Takamiya, R., Takahashi, M., Freeman M.R. and Taniguchi, N. (2007) Acrolein induces cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells: roles of p38 MAP kinase and protein kinase Cd. Arteriosclerosis, Thrombosis, and Vascular Biology. 27:1319-1325; Epub ahead of print, Mar 15.

Freeman, M.R., Cinar, B., Kim, J., Mukhopadhyay, N.K., Vizio, D.D., Adam, R.M., and Solomon, K.R. (2007) Transit of Hormonal and EGF receptor-dependent Signals Through Cholesterol-rich Membranes. Steroids. 72:210-217

Kim, J., Adam, R.M., and Freeman, M.R. (2005) Trafficking of nuclear HB-EGF into an epidermal growth factor receptor-dependent autocrine loop in response to oxidative stress. Cancer Res. 65:8242-8249.

Zhuang, L.,* Kim, J.,* Adam, R.M., Solomon, K.R., and Freeman, M.R. (2005) Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. Journal of Clinical Investigation 115:959-968. *Co-first authors.

Kim, J., Lin, J., Adam, R.M., Lamb, C., Shively, S.B., and Freeman, M.R. (2005) An oxidative stress mechanism mediates chelerythrine-induced heparin-binding EGF-like growth factor ectodomain shedding. Journal of Cellular Biochemistry 94(1):39-49.

Kim, J., Adam, R.M., Solomon, K.R. and Freeman, M.R. (2004) Involvement of cholesterol-rich lipid rafts in interleukin-6-induced neuroendocrine differentiation of LNCaP prostate cancer cells. Endocrinology 145(2):613-619.

Kim, J., and Freeman, M.R. (2003) JNK/SAPK mediates doxorubicin-induced differentiation and apoptosis of MCF-7 breast cancer cells. Breast Cancer Res. and Treatment 79:321-328.

Adam, R.M., Kim, J.Y., Freeman, M.R. (2002) Heparin-binding EGF-like growth factor stimulates androgen-independent prostate tumor growth and antagonizes androgen receptor function. Endocrinology 143: 4599-4608.

Kim, J., Adam, R.M., and Freeman, M.R. (2002) Activation of the Erk mitogen-activated protein kinase pathway stimulates neuroendocrine differentiation in LNCaP cells independently of cell cycle withdrawal and STAT3 phosphorylation. Cancer Research 62: 1549-1554.

Chen, Y.K., Kim, J.Y., Woo, H.J., Oh, S.M., Kang, I.S., Ha, J., Kim, S.S. (2000) No significant correlation exists between core promoter mutations, viral replication, and liver damage in chronic hepatitis B infection. Hepatology 32(5): 1154-1162.

Chen, Y.K., Kim, J.Y., and Kim, S.S. (2000) Phosphatidylinositol 3-kinase stimulates muscle differentiation by activating p38 mitogen-activated protein kinase. Biochemical and Biophysical Research Communications 276: 502-507.

Kim, B.C., Lee, M.N., Kim, J.Y., Chang, J.D., Kim, S.S., Lee, S.Y., and Kim, J.H. (1999) Role of PI3-kinase and Rac in the nuclear signaling by tumor necrosis factors-alpha in Rat-2 fibroblasts. Journal of Biological Chemistry 274: 24372-24377.

Kim, J.M., Yoon, M., Kim, J.Y., Kim, S.S., Kang, I., Ha, J., and Kim, S.S. (1999) Phosphatidylinositol 3-kinase regulated differentiation of H9c2 cardiomyoblasts mainly through the protein kinase B/ Akt- independent pathway. Archives of Biochemistry and Biophysics 367: 67-73.

Park, C.E., Kim, S.M., Kim, J.M., Yoon, M., Kim, J.Y., Kang, I., Kim, S.S. and Ha, J. (1998) Rapid increase of cytosolic contents of acetyl-Co A carboxylase isoforms in H9c2 cells by short term treatment with insulin and okadaic acid. Experimental and Molecular Medicine 30: 73-79.

Keum, W.K., Kim, J.Y., Chi, S.G., Woo, H.J., Kim, S.S., Ha, J., and Kang, I. (1998) Heterogeneous HBV mutants coexist in Korean hepatitis B patients. Experimental and Molecular Medicine 30: 115-122.\

Khil, L.Y., Kim, J.Y., Yoon, J.B., Kim, J.M., Keum, W.K., Kim, T., Yoon, Y., Yoon, M., Moon, C., Lee, J., Ha, J., Kim, S.S. and Kang, I.S. (1997) Insulin Has a Limited Effect on the Cell Cycle Progression in 3T3 L1 Fibroblasts. Molecules and Cells 7: 742-748.