Vanderbilt University School of Medicine

Jiang, Ming , M.D., Ph.D.
Research Associate Professor of Medicine

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Phone Number: 615-343-0797/615-936-0222


Jiang, Ming's picture

Office Address   Mailing Address

2525 West End Avenue, Suite 334D / B 2120, MCN

Division of Epidemiology, Suite 334 37203-1738

Research Keywords
Prostate Carcinogenesis; Prostate Cancer Metastasis; BPH; Nuclear Receptors; PPARgamma; PTEN; Cancer Metabolism; Autophagy; Arachidonic Acid Metabolism; COXs and LOXs; Lipotoxicity; Cellular Immortalization; Prostate Stem and Progenitor Cells; Inducible Conditional Gene Knockout Mouse Model; Tissue Recombination-Xenografting Mouse Model.

Research Specialty
Prostate pathogenesis; Stem and progenitor cells; Nuclear receptor and cell metabolism; PPARgamma and PTEN; Cell differentiation and autophagy; Establishment of a paired prostate epithelial and stromal cell lines NHPrE1, BHPrE1 and BHPrS1; Human endothelial cell line iHDME1; In vivo functional reconstructive human prostatic glandular tissues in a mouse model; PSA-Cre-ERT2, an inducible conditional gene knockout mouse model in prostate.

Research Description
Dr. Ming Jiang's research interests are focused on three main topics:
1. Cross-talk of the Arachidonic Acid/COXs/LOXs/PPARgamma signaling pathway during prostatic pathogenesis:
Epidemiological studies and animal experiments suggested a close link between dietary fat intake and the risk of prostate cancer. Omega-6 fatty acid, such as linoleic acid (LA), arachidonic acid (AA) and the AA metabolite prostaglandin E2 (PGE2) have been found to stimulate tumor growth. In contrast, oleic acid (OA) and omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited tumor growth. Eicosanoid synthesis involves the release of AA from cell membrane phospholipids by an enzyme called phospholipase A2 (PLA2). AA then undergoes metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs). Peroxisome proliferator-activated receptors (PPARs) are the ligand activated transcription factors belonging to the nuclear receptor superfamily. The PPAR family is composed of PPARalpha, PPARbeta/delta and PPARgamma. PPARgamma can be activated by docosahexanoic acid, certain nature prostaglandin metabolite 15-deoxy-delta 12, 15-prostaglandin J2 (15dPGJ2), 15-hydroxyeicosatetraenoic acid (15-HETE), polyunsaturated fatty acid (PUFA), nonsteroidal anti-inflammatory drugs (NSAID), and members of the thiazolinedione family. We are interested in understanding the roles played by changes in arachidonic acid metabolism and gene regulation in the pathogenesis of benign prostatic hyperplasia (BPH) and prostatic intraepithelial neoplasia (PIN), the presumptive precursor to prostate cancer. Changes in arachidonic acid metabolism and specifically a loss of 15-LOX-2 activity (the enzyme which generates the PPARgamma ligand 15-HETE in the human prostate) are a common early feature of prostate cancer. These changes are proposed to result in a reduction or loss of PPARgamma signaling early in the prostatic disease process. COX-2 expression is down-regulated by a negative feedback loop mediated through PPARgamma which has tissue-specific distribution and links the control of cellular fatty acid metabolism, peroxisomal and lysosomal maturation and differentiation. We have used PB-Cre4 and PPARgamma-floxed mice to generate male mice in which the PPARgamma gene (coding for both the PPARgamma1 and gamma2 isoforms) is excised in the prostatic luminal epithelium. These mice developed mouse prostatic intraepithelial neoplasia (mPIN) lesions as early as 3 months of age. A similar phenotype was also seen in a tissue recombination model in which shRNA was used to remove specifically the PPARgamma2 isoform in wild-type mouse prostatic epithelial cells (mPrE). These experiments confirm that loss of epithelial PPARgamma signaling is sufficient to give rise to premalignant lesions in the prostate due to increased oxidative stress and active autophagy.

2. Functional remodeling of human normal/benign prostatic glandular tissues in a mouse model:
We have established a number of spontaneously immortalized human prostate epithelial progenitor (HPrE) and stromal (HPrS) cell lines from normal and benign samples. Tissue recombinants made using HPrE cells and rat fetal urogenital sinus mesenchyme (UGM) showed functional well-differentiated prostatic glandular formation when grafted under the renal capsule of immunodeficient SCID mice for three months. Interestingly they also showed expression of the prostatic biomarkers, PSA, 15-LOX-2, AR and p63 proteins expression in the reconstituted epithelial luminal or basal cell layer. We are exploring gene functions using the genetic modification targeted at the human prostate cells in vitro and then investigating resultant phenotypes in a tissue recombination model in vivo.

3. Establishment of a spontaneous human prostate cancer-mouse multi-organ including bone metastasis model:
We have established a novel intraductal mouse anterior prostate (AP)-orthotopic xenografting model of prostate cancer metastasis. Following grafting to the AP, both osteoblastic and osteolytic pathogenesis induced by PC-3 cells was observed in the spine and femur of immunodeficient SCID mice. Cancer cell invasion and metastasis were initiated at the mouse primary periprostatic microvessels and spread to the distant vertebral microvessels and bone tissues in a stepwise and time-dependent progression. The intravasation and extravasation of cancer cells depend on their invasive abilities and the properties of host endothelial cell barrier. We are interested in targeting angiogenic growth-related factors by using newly developed inhibitors to enhance endothelial barrier function, preventing vascular permeability and angiogenesis and promoting vascular regression to inhibit prostate cancer bone metastasis. This model is not only amenable to testing agents which may have effects on cancer cells intravasation, metastasis, and extravasation, but also intended for examining the biology of prostate cancer metastases at the bone site.

Lehmann, BD, Ding, Y, Viox, DJ, Jiang, M, Zheng, Y, Liao, W, Chen, X, Xiang, W, Yi, Y. Evaluation of public cancer datasets and signatures identifies TP53 mutant signatures with robust prognostic and predictive value. BMC Cancer, 15(1), 179, 2015.

Lin, SJ, Yang, DR, Wang, N, Jiang, M, Miyamoto, H, Li, G, Chang, C. TR4 nuclear receptor enhances prostate cancer initiation via altering the stem cell population and EMT signals in the PPARG-deleted prostate cells. Oncoscience, 2(2), 142-50, 2015.

Liu, LL, Xian, H, Cao, JC, Zhang, C, Zhang, YH, Chen, MM, Qian, Y, Jiang, M. Peroxisome proliferator-activated receptor gamma signaling in human sperm physiology. Asian J Androl, , , 2015.

Ren P, Zhang Y, Huang Y, Yang Y, Jiang M.. Functions of Peroxisome Proliferator-Activated Receptor Gamma (PPAR??) in Gynecologic Disorders.. Clin Med Insights Oncol., 9, 43-49, 2015.

Hansen, AG, Arnold, SA, Jiang, M, Palmer, TD, Ketova, T, Merkel, A, Pickup, M, Samaras, S, Shyr, Y, Moses, HL, Hayward, SW, Sterling, JA, Zijlstra, A. ALCAM/CD166 is a TGF-??-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res, 74(5), 1404-15, 2014.

Strand, DW, DeGraff, DJ, Jiang, M, Sameni, M, Franco, OE, Love, HD, Hayward, WJ, Lin-Tsai, O, Wang, AY, Cates, JM, Sloane, BF, Matusik, RJ, Hayward, SW. Deficiency in metabolic regulators PPAR?? and PTEN cooperates to drive keratinizing squamous metaplasia in novel models of human tissue regeneration. Am J Pathol, 182(2), 449-59, 2013.

Xiang, Y, Qiu, Q, Jiang, M, Jin, R, Lehmann, BD, Strand, DW, Jovanovic, B, DeGraff, DJ, Zheng, Y, Yousif, DA, Simmons, CQ, Case, TC, Yi, J, Cates, JM, Virostko, J, He, X, Jin, X, Hayward, SW, Matusik, RJ, George, AL, Yi, Y. SPARCL1 suppresses metastasis in prostate cancer. Mol Oncol, 7(6), 1019-30, 2013.

Lee, SO, Tian, J, Huang, CK, Ma, Z, Lai, KP, Hsiao, H, Jiang, M, Yeh, S, Chang, C. Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells. J Endocrinol, 213(2), 173-82, 2012. PMCID:3335843

Pruitt, FL, He, Y, Franco, OE, Jiang, M, Cates, JM, Hayward, SW. Cathepsin D acts as an essential mediator to promote malignancy of benign prostatic epithelium. Prostate, , , 2012.

Strand, DW, Jiang, M, Murphy, TA, Yi, Y, Konvinse, KC, Franco, OE, Wang, Y, Young, JD, Hayward, SW. PPARI? isoforms differentially regulate metabolic networks to mediate mouse prostatic epithelial differentiation. Cell Death Dis, 3, e361, 2012.

Wang, H, Jiang, M, Cui, H, Chen, M, Buttyan, R, Hayward, SW, Hai, T, Wang, Z, Yan, C. The Stress Response Mediator ATF3 Represses Androgen Signaling by Binding the Androgen Receptor. Mol Cell Biol, 32(16), 3190-202, 2012.

Franco, OE, Jiang, M, Strand, DW, Peacock, J, Fernandez, S, Jackson, RS, Revelo, MP, Bhowmick, NA, Hayward, SW. Altered TGF-I? signaling in a subpopulation of human stromal cells promotes prostatic carcinogenesis. Cancer Res, 71(4), 1272-81, 2011. PMCID:3076790

Jiang, M. Interplay between autophagy and metabolism in Ras mutation-induced tumorigenesis. Asian J Androl, 13(4), 610-1, 2011.

Jiang, M, Strand, DW, Franco, OE, Clark, PE, Hayward, SW. PPARI?: a molecular link between systemic metabolic disease and benign prostate hyperplasia. Differentiation, 82(4-5), 220-36, 2011.

Jiang, M, Fernandez, S, Jerome, WG, He, Y, Yu, X, Cai, H, Boone, B, Yi, Y, Magnuson, MA, Roy-Burman, P, Matusik, RJ, Shappell, SB, Hayward, SW. Disruption of PPARgamma signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy. Cell Death Differ, 17(3), 469-81, 2010. PMCID:2821953

Jiang, M, Jerome, WG, Hayward, SW. Autophagy in nuclear receptor PPARgamma-deficient mouse prostatic carcinogenesis. Autophagy, 6(1), 175-6, 2010.

Jiang, M, Min, Y, Debusk, L, Fernandez, S, Strand, DW, Hayward, SW, Lin, PC. Spontaneous immortalization of human dermal microvascular endothelial cells. World J Stem Cells, 2(5), 114-20, 2010. PMCID:3097930

Jiang, M, Strand, DW, Fernandez, S, He, Y, Yi, Y, Birbach, A, Qiu, Q, Schmid, J, Tang, DG, Hayward, SW. Functional Remodeling of Benign Human Prostatic Tissues In Vivo by Spontaneously Immortalized Progenitor and Intermediate Cells. Stem Cells, 28(2), 344-356, 2010.

Li, H, Jiang, M, Honorio, S, Patrawala, L, Jeter, CR, Calhoun-Davis, T, Hayward, SW, Tang, DG. Methodologies in assaying prostate cancer stem cells. Methods Mol Biol, 568, 85-138, 2009.

Yu, X, Wang, Y, Jiang, M, Bierie, B, Roy-Burman, P, Shen, MM, Taketo, MM, Wills, M, Matusik, RJ. Activation of beta-Catenin in mouse prostate causes HGPIN and continuous prostate growth after castration. Prostate, 69(3), 249-62, 2009.

Bhatia, B, Jiang, M, Suraneni, M, Patrawala, L, Badeaux, M, Schneider-Broussard, R, Multani, AS, Jeter, CR, Calhoun-Davis, T, Hu, L, Hu, J, Tsavachidis, S, Zhang, W, Chang, S, Hayward, SW, Tang, DG. Critical and distinct roles of p16 and telomerase in regulating the proliferative life span of normal human prostate epithelial progenitor cells. J Biol Chem, 283(41), 27957-72, 2008. PMCID:2562067

Ratnacaram, CK, Teletin, M, Jiang, M, Meng, X, Chambon, P, Metzger, D. Temporally controlled ablation of PTEN in adult mouse prostate epithelium generates a model of invasive prostatic adenocarcinoma. Proc Natl Acad Sci U S A, 105(7), 2521-6, 2008. PMCID:2268169

He, Y, Franco, OE, Jiang, M, Williams, K, Love, HD, Coleman, IM, Nelson, PS, Hayward, SW. Tissue-specific consequences of cyclin D1 overexpression in prostate cancer progression. Cancer Res, 67(17), 8188-97, 2007.

Indra, AK, Castaneda, E, Antal, MC, Jiang, M, Messaddeq, N, Meng, X, Loehr, CV, Gariglio, P, Kato, S, Wahli, W, Desvergne, B, Metzger, D, Chambon, P. Malignant transformation of DMBA/TPA-induced papillomas and nevi in the skin of mice selectively lacking retinoid-X-receptor alpha in epidermal keratinocytes. J Invest Dermatol, 127(5), 1250-60, 2007.

Gao, N, Ishii, K, Mirosevich, J, Kuwajima, S, Oppenheimer, SR, Roberts, RL, Jiang, M, Yu, X, Shappell, SB, Caprioli, RM, Stoffel, M, Hayward, SW, Matusik, RJ. Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation. Development, 132(15), 3431-43, 2005.

Metzger, D, Imai, T, Jiang, M, Takukawa, R, Desvergne, B, Wahli, W, Chambon, P. Functional role of RXRs and PPARgamma in mature adipocytes. Prostaglandins Leukot Essent Fatty Acids, 73(1), 51-8, 2005.

Jiang, M, Shappell, SB, Hayward, SW. Approaches to understanding the importance and clinical implications of peroxisome proliferator-activated receptor gamma (PPARgamma) signaling in prostate cancer. J Cell Biochem, 91(3), 513-27, 2004.

Wan, XW, Jiang, M, Cao, HF, He, YQ, Liu, SQ, Qiu, XH, Wu, MC, Wang, HY. The alteration of PTEN tumor suppressor expression and its association with the histopathological features of human primary hepatocellular carcinoma. J Cancer Res Clin Oncol, 129(2), 100-6, 2003.

Wan, XW, Wang, HY, Jiang, M, He, YQ, Liu, SQ, Cao, HF, Qiu, XH, Tang, L, Wu, MC. [PTEN expression and its significance in human primary hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi, 11(8), 490-2, 2003.

Imai, T, Jiang, M, Chambon, P, Metzger, D. Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes. Proc Natl Acad Sci U S A, 98(1), 224-8, 2001. PMCID:14572

Imai, T, Jiang, M, Kastner, P, Chambon, P, Metzger, D. Selective ablation of retinoid X receptor alpha in hepatocytes impairs their lifespan and regenerative capacity. Proc Natl Acad Sci U S A, 98(8), 4581-6, 2001. PMCID:31877

Wu, J, Shen, ZZ, Lu, JS, Jiang, M, Han, QX, Fontana, JA, Barsky, SH, Shao, ZM. Prognostic role of p27Kip1 and apoptosis in human breast cancer. Br J Cancer, 79(9-10), 1572-8, 1999. PMCID:2362719

Jiang, M, Shao, Z, Wu, J. [WAF1/CIP1/p21 gene in wild type p53 and mutant p53 human breast cancer cell lines in relation to its cytobiological features. Zhonghua Zhong Liu Za Zhi, 20(3), 181-4, 1998.

Jiang, M, Shao, Z, Zhang, Y. [Study on p53, mdm-2 and p21WAF1 protein expression in ER-positive and ER-negative human breast cancer cell lines and its relation to biological features. Zhonghua Bing Li Xue Za Zhi, 26(6), 327-30, 1997.

Jiang, M, Shao, ZM, Wu, J, Lu, JS, Yu, LM, Yuan, JD, Han, QX, Shen, ZZ, Fontana, JA. p21/waf1/cip1 and mdm-2 expression in breast carcinoma patients as related to prognosis. Int J Cancer, 74(5), 529-34, 1997.

Shao, Z, Jiang, M, Yu, L, Han, Q, Shen, Z. Estrogen receptor-negative breast cancer cells transfected with estrogen receptor exhibit decreased tumour progression and sensitivity to growth inhibition by estrogen. Chin Med Sci J, 12(1), 11-4, 1997.

Shao, Z, Jiang, M, Yu, L, Han, Q, Shen, Z. p53 independent G1 arrest and apoptosis induced by adriamycin. Chin Med Sci J, 12(2), 71-5, 1997.

Wu, J, Shao, Z, Jiang, M. [In situ DNA labeling apoptosis in breast cancer as related to prognosis. Zhonghua Zhong Liu Za Zhi, 19(2), 100-2, 1997.

Shao, Z, Jiang, M, Wu, J, Yu, L, Han, Q, Zhang, T, Shen, Z. Inhibition of spontaneous apoptosis in human breast cancer. Chin Med Sci J, 11(4), 200-3, 1996.

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