Leland W. K. Chung, Ph.D.
Professor
& Director
Molecular Urology and Therapeutics Program
Department of Urology
Contact Information
Department of Urology
Emory University School of Medicine
Clinic B, Suite 5101
1365 Clifton Road, N.E.
Atlanta, GA 30322
Phone: 404-778-3672
Fax: 404-778-3965
Email: lwchung@emory.edu
Education
BS, National Taiwan University,
1962, Agricultural Chemistry
MS, Oregon State University, 1965, Biochemistry
PhD, University of Oregon Medical School, 1969, Pharmacology
Research Interests
Dr. Leland W. K. Chung serves as the Program Director for delineating tumor-microenvironment interaction with particular emphasis on extracellular matrix (ECM) integrin signaling that affects tumor growth, migration invasion and metastasis. Studies are focused on characterizing integrin usage as prostate cancer proceeds from androgen-dependent to its androgen-independent state, using a cell model of prostate carcinogenesis. Tissue-specific and tumor-restrictive promoters are identified and cloned through cDNA microarray, using lineage-related human prostate cancer cell lines, and relevant genes will be cloned, characterized, and validated in clinical specimens. Efforts are made to co-target tumor and its microenvironment using adenoviral vectors and anti-angiogenic modifiers. To improve the understanding of prostate cancer bone metastasis and efficacy of molecular targeting, we are developing novel 3-D and transgenic models by delivering growth factor and extracellular matrices as chemoattractins for prostate cancer bone metastasis. Furthermore, various approaches are developed to image prostate cancer at both primary and distant metastatic sites using non-invasive imaging techniques.
Selected Publications
Camps JL, Chang SM, Hsu TC, Freeman MR, Hong SJ, Zhau HYE, von Eschenbach AC, and Chung LWK. Fibroblast-mediated acceleration of human epithelial tumor growth in vivo. Proc. Natl. Acad. Sci. 87(1):75-79, 1990.
Gleave ME, Hsieh JT, Gao C, von Eschenbach AC, and Chung LWK. Acceleration of human prostate cancer growth in vivo by prostate and bone fibroblasts. Cancer Res. 51:3753-3761, 1991.
Hsieh JT, Zhau HYE, Wang XH, Liew CC, and Chung LWK. Regulation of basal- and luminal-specific cytokeratin expression in rat accessory sex organs: Evidence for a new class of androgen-repressed genes and insight into their pairwise control. J. Biol. Chem. 267:2303-2310, 1992.
Gleave ME, Hsieh JT, Wu HC, von Eschenbach AC, and Chung LWK. Serum prostate specific antigen levels in mice bearing human prostate LNCaP tumors are determined by tumor volume and endocrine and growth factors. Cancer Res. 52:1598-1605, 1992.
Chung LWK, Li W, Gleave M, Hsieh JT, Wu HC, Sikes RA, Zhau HYE, Bandyk M, Logothetis C, Rubin JS, and von Eschenbach AC. Human Prostate Cancer Model: Roles of Growth Factors
and Extracellular Matrices. J. of Cell. Biochem. 16H:99-105, 1992.
Hsieh JT, Wu HC, Gleave ME, von Eschenbach AC, and Chung LWK. Autoregulation of prostate-specific antigen and prostatic-specific antigen in human prostate cancer. Cancer Res. 53:2852-2857, 1993.
Thalmann GN, Anezinis PE, Chang S-M, Zhau HYE, Kim E, Hopwood VL, Pathak S, von Eschenbach AE, and Chung LWK. Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res. 54:2577-2581, 1994.
Chung LWK. The role of stromal-epithelial interaction in normal and malignant growth. Cancer Surv., 23: 33-42, 1995.
Zhau HYE, Chang S-M, Chen B-Q, Wang Y, Zhang H, Kao C, Sang QA, Pathak SJ, and Chung LWK. Androgen-repressed phenotype in human prostate cancer. Proc. Natl. Acad. Sci. 93:15152-15157, 1996.
Ko S-C, Cheon J, Kao C, Gotoh A, Shirakawa T, Sikes RA, Karsenty G, and Chung LWK. Osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma in experimental models. Cancer Res. 56:4614-4619, 1996.
Zhau HYE, Goodwin TJ, Chang S-M, Baker TL, and Chung LWK. Establishment of a 3-dimensional human prostate organoid co-culture under microgravity-simulated conditions: Evaluation of androgen-induced growth and PSA expression. In Vitro Cell Dev. Biol. 33:375-380, 1997.
Cleutjens KB, van der Korput HA, Ehren-van Eekelen CC, Sikes RA, Fasciana C, Chung LWK, and Trapman J. A 6-kb promoter fragment mimics in transgenic mice the prostate-specific and androgen-regulated expression of the endogenous prostate-specific antigen gene in humans. Mol. Endocrinol. 11:1256-1265, 1997.
Wu TT, Sikes RA, Cui Q, Thalmann GN, Kao C, Murphy CF, Yang H, Zhau HYE, Balian G and Chung LWK. Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines. Int. J. Cancer 77: 887-894, 1998.
Sokoloff, M. H. and Chung, LWK Targeting angiogenic pathways involving tumor-stromal interaction to treat advanced human prostate cancer. Cancer Metastasis Rev. 17: 307-315, 1998.
Gotoh, A., Ko, S. C., Shirakawa, T., Cheon, J., Kao, C., Miyamoto, T., Gardner, T. A., Ho, L. J., Cleutjens, C. B., Trapman, J., Graham, F. L., and Chung, LWK. Development of prostate-specific antigen promoter-based gene therapy for androgen-independent human prostate cancer. J. Urol. 160: 220-229, 1998.
Thalmann GN, Sikes RA, Devoll RE, Kiefer JA, Markwalder R, Klima I, Farach-Carson CM, Studer UE, Chung LWK. Osteopontin: possible role in prostate cancer progression. Clinical Cancer Res. 5(8): 2271-7, 1999.
Koeneman K, Yeung F, and Chung LWK. Osteomimetic properties of prostate cancer cells: A hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment. The Prostate 39(4):246-261, 1999.
Degeorges A, Wang F, Frierson HF, Jr, Seth A, Chung LWK, and Sikes RA. Human prostate cancer expresses the low affinity insulin-like growth factor binding protein IGFBP-rP1. Cancer Res. 59(12):2787-90, 1999.
Yeung F, Li X, Ellett J, Trapmand J, Kao C and Chung LWK. Regions of prostate-specific antigen (PSA) promoter confer androgen-independent expression of PSA in prostate cancer cells. J. Biol. Chem. 275:40846-55, 2000.
Thalmann GN, Sikes RA, Wu TT., Degeorges A, Chang SM, Ozen M, Pathak S, and Chung LWK. LNCaP progression model of human prostate cancer: androgen-independence and osseous metastasis. Prostate 44:91-103, 2000.
Edlund M, Miyamoto T, Sikes RA, Ogle R, Laurie GW, Farach-Carson MC, Otey CA, Zhau HE and Chung LWK. Integrin expression and usage by prostate cancer cell lines on laminin substrata. Cell Growth & Different. 12:99-107, 2001.
Matsubara S, Wada Y, Gardner TA, Egawa M. Park MS, Hsieh CL, Zhau HE, Kao C, Kamidono S, Gillenwater JY and Chung LWK. A conditional replication-competent adenoviral vector, Ad-OC-E1a, to cotarget prostate cancer and bone stroma in an experimental model of androgen-independent prostate cancer bone metastasis. Cancer Res. 61(16):6012-9, 2001.
Rhee HW, Zhau HE, Pathak S. Multani As, Pennanen S, Visakorpi T, Chung LWK Permanent phenotypic and genotypic changes of prostate cancer cell cultured in a three-dimensional rotating-wall vessel. In Vitro Cellular & Developmental Biology Animal 37(3):127-40, 2001.
Yeung F, Law WK, Yeh CH, Westendorf JJ, Zhang Y, Wang R, Kao C, Chung LWK. Regulation of human osteocalcin promoter in hormone-independent human prostate cancer cells. J. Biol. Chem. 277: 2468-2476, 2002.
Tang S, Bhatia B, Maldonado CJ, Yang P, Newman RA, Liu J, Chandra D, Traag J, Klein RD, Fischer SM, Chopra D, Shen J, Zhau HE, Chung LWK, Tang DG. “Evidence that arachidonate 15-lipoxygenase 2 is a negative cell cycle regulator in normal prostate epithelial cells”. J. Biol. Chem. 277:18 16189-1620, 2002.
Sung S-Y, Chung LWK. Prostate Carcinoma-Stroma Interaction: Molecular Mechanisms and Opportunities for Therapeutic Targeting. Differentiation 70:506-521, 2002.
Chung LWK. Prostate carcinoma bone-stroma interaction and its biologic and therapeutic implications. Cancer 97:772-778, 2003.
Kubo H, Gardner TA, Wada Y, Koeneman KS, Gotoh A, Yang L, Kao C, Lim SD, Amin MB, Yang H, Black ME, Matsubara S, Nakagawa M, Gillenwater JY, Zhau HYE, Chung LWK. Phase I Dose-Escalation Clinical Trial of Osteocalcin Promoter-Driven Herpes Simplex Virus Thymidine Kinase Adenovirus in Localized and Metastatic Hormone Refractory Prostate Cancer. Human Gene Ther. J. 14:227-241, 2003.
Cinar B, Yeung F, Konaka H, Mayo MW, Freeman MR, Zhau HYE and Chung LWK. Identification of a negative regulatory cis-element in the enhancer core region of the Prostate Specific Antigen (PSA) promoter: Implications for intersection of androgen receptor and NP-kappaB signaling in prostate cancer cells. Biochem. J. 379:421-31, 2004
Wang RX, Xu JC, Saramäki O, Visakorpi T, Sutherland WM, Zhou JG, Sen B, Lim SD, Mabjeesh N, Amin M, Dong J-T, Petros JA, Nelson PS, Marshall FF, Zhau HYE and Chung LWK. PrLZ, a novel prostate-specific and androgen-responsive gene of the TPD52 family, amplified in chromosome 8q21.1 and over-expressed in human prostate cancer. Cancer Res. 64:1589-1594, 2004.
Edlund M, Sung, S-Y and Chung LWK. Modulation of prostate cancer growth in bone microenvironments. J. Cell. Biochem. 91:686-705, 2004.
Gao X, Cui YY, Levenson
RM, Chung LWK and Nie S. In vivo cancer targeting and imaging with semiconductor
quantum dots. Nature Biotech. 22:969-976, 2004.
Chung LWK, Baseman A, Assikis V and Zhau HYE. Molecular insights into
prostate cancer progression: The missing link of tumor microenvironment.
J. Urol. 173: 10-20. 2005.
Huang W-C, Xie Z, Konaka H, Sodek J, Zhau HYE, and Chung LWK. Identification and characterization of a CRE cis-element within human osteocalcin and bone sialoprotein promoters mediating osteomimicry of prostate cancer cells: role of cAMP-dependent PKA signaling pathway. Can. Res. 65(6):2303-2313, 2005.
Hsieh CL, Xie Z, Liu ZY, Green JE, Martin WD, Datta MW, Yeung F, Pan D, Chung LWK. A luciferase transgenic mouse model: visualization of prostate development and its androgen responsiveness in live animals. Mol Endocrinol. 35(2):293-304, 2005.
Jin F, Liu X, Zhou Z, Yue P, Lotan R, Khuri FR, Chung LWK, Sun SY. Activation of nuclear factor-kappaB contributes to induction of death receptors and apoptosis by the synthetic retinoid CD437 in DU145 human prostate cancer cells. Cancer Res. 65(14):6354-63, 2005.
Xu J, Wang R, Xie ZH, Odero-Marah V, Pathak S, Multani A, Chung LW, Zhau HE. Prostate cancer metastasis: Role of the host microenvironment in promoting epithelial to mesenchymal transition and increased bone and adrenal gland metastasis. Prostate. 66(15):1664-73, 2006.
Huang WC, Wu D, Xie Z, Zhau HE, Nomura T, Zayzafoon M, Pohl J, Hsieh CL, Weitzmann MN, Chung LW. ?2-Microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. Cancer Res. 66(18):9108-16, 2006.
Sung SY, Kubo H, Shigemura K, Arnold RS, Logani S, Wang R, Konaka H, Nakagawa M, Mousses S, Amin M, Anderson C, Johnstone P, Petros JA, Marshall FF, Zhau HE, Chung LW. Oxidative stress induces ADAM9 protein expression in human prostate cancer cells. Cancer Res. 66(19):9519-26, 2006.
Nomura T, Huang WC, Zhau HE, Wu D, Xie Z, Mimata H, Zayzafoon M, Young AN, Marshall FF, Weitzmann MN, Chung LW.Beta2-microglobulin promotes the growth of human renal cell carcinoma through the activation of the protein kinase A, cyclic AMP-responsive element-binding protein, and vascular endothelial growth factor axis. Clin Cancer Res. 12(24):7294-305, 2006.
Hsieh CL, Xie Z, Yu J, Martin WD, Datta MW, Wu GJ, Chung LW. (2007). Non-invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model. Prostate. 67(7):685-91.
Nomura T, Huang WC, Seo S, Zhau HE, Mimata H, Chung LW.Targeting beta2-microglobulin mediated signaling as a novel therapeutic approach for human renal cell carcinoma. J Urol. 178(1):292-300, 2007