Office Address:
2525 West End - Suite 800, Nashville, TN 37232-2765

Research Associate Professor of Medicine

Relevant Links

Clinical Interest

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 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 oste

Publications

Huang Yuejiao, Cheng Chun, Zhang Chong, Zhang Yonghui, Chen Miaomiao, Strand Douglas W., Jiang Ming. Advances in prostate cancer research models: From transgenic mice to tumor xenografting models. Asian Journal of Urology. 2016 Mar 3/2/2016; 1-11. Available from: http://www.sciencedirect.com/science/article/pii/S2214388216300029., 2016.

Zhai W, Sun Y, Jiang M, Gasiewicz T A., Zheng J, Chang C. Differential regulation of LncRNA-SARCC suppresses VHL-mutant RCC cell proliferation yet promotes VHL-normal RCC cell proliferation via modulating androgen receptor/HIF-2a/C-MYC axis under hypoxia. Oncogene. 2016 Mar 3/14/2016; Available from: http://www.nature.com.proxy.library.vanderbilt.edu/onc/journal/vaop/ncurrent/full/onc201619a.html., 2016.

Tao L, Qiu J, Jiang M, Song W, Yeh S, Yu H, Zang L, Xia S, Chang C. Infiltrated T cells promote bladder cancer progression via increasing IL-1¿androgen receptor (AR)¿HIF-1a¿VEGFa signals. Mol. Cancer Ther [print-electronic]. 2016 May 5/11/2016; PMID: 27196763, PII: 1535-7163.MCT-15-0306, DOI: 10.1158/1535-7163.MCT-15-0306, ISSN: 1538-8514. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27196763., 2016.

Yang S, Jiang M, Grabowska MM, Li J, Connelly ZM, Zhang J, Hayward SW, Cates JM, Han G, Yu X. Androgen receptor differentially regulates the proliferation of prostatic epithelial cells in vitro and in vivo. Oncotarget [print-electronic]. 2016 Sep 9/7/2016; PMID: 27611945, PII: 11879, DOI: 10.18632/oncotarget.11879, ISSN: 1949-2553. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27611945., 2016.

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. 2015; 15: 179. PMID: 25886164, PMCID: PMC4404582, PII: 10.1186/s12885-015-1102-7, DOI: 10.1186/s12885-015-1102-7, ISSN: 1471-2407. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25886164., 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. 2015; 2(2): 142-50. PMID: 25859557, PMCID: PMC4381707, ISSN: 2331-4737. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25859557., 2015.

Ren P, Zhang Y, Huang Y, Yang Y, Jiang M.. Functions of Peroxisome Proliferator-Activated Receptor Gamma (PPARg) in Gynecologic Disorders. Clin Med Insights Oncol. 2015 Apr 4/27/2015; 27(9): 43-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=DetailsSearch&Term=25987855%5Buid%5D., 2015.

Zhu X, Shrubsole MJ, Ness RM, Hibler EA, Cai Q, Long J, Chen Z, Li G, Jiang M, Hou L, Kabagambe EK, Zhang B, Smalley WE, Edwards TL, Giovannucci EL, Zheng W, Dai Q. Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study. Mol. Carcinog [print-electronic]. 2015 Aug 8/31/2015; PMID: 26333203, DOI: 10.1002/mc.22387, ISSN: 1098-2744. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26333203., 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 Nov; 17(6): 942-7. PMID: 25851655, PII: 150253, DOI: 10.4103/1008-682X.150253, ISSN: 1745-7262. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25851655., 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-ß-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res [print-electronic]. 2014 Mar 3/1/2014; 74(5): 1404-15. PMID: 24385212, PMCID: PMC4149913, PII: 0008-5472.CAN-13-1296, DOI: 10.1158/0008-5472.CAN-13-1296, ISSN: 1538-7445. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24385212., 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 [print-electronic]. 2013 Feb; 182(2): 449-59. PMID: 23219716, PMCID: PMC3562729, PII: S0002-9440(12)00801-2, DOI: 10.1016/j.ajpath.2012.10.007, ISSN: 1525-2191. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23219716., 2013.

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 [print-electronic]. 2013 Apr; 73(5): 476-88. PMID: 22996917, PMCID: PMC3594371, DOI: 10.1002/pros.22589, ISSN: 1097-0045. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22996917., 2013.

Jiang Ming, Williams Karin, Hayward Simon W.. Stem Cells Handbook: "Chapter 16. Glandular Stem Cells (GSCs): Stem Cells in Glandular Organs (pp. 223-233)". Stewart Sell. [place unknown]: Springer New York; 2013 Jul 7/3/2013. Available from: http://link.springer.com/chapter/10.1007/978-1-4614-7696-2_16., 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 [print-electronic]. 2013 Dec; 7(6): 1019-30. PMID: 23916135, PMCID: PMC3838491, PII: S1574-7891(13)00105-1, DOI: 10.1016/j.molonc.2013.07.008, ISSN: 1878-0261. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23916135., 2013.

Strand DW, Jiang M, Murphy TA, Yi Y, Konvinse KC, Franco OE, Wang Y, Young JD, Hayward SW. PPAR¿ isoforms differentially regulate metabolic networks to mediate mouse prostatic epithelial differentiation. Cell Death Dis. 2012; 3: e361. PMID: 22874998, PMCID: PMC3434663, PII: cddis201299, DOI: 10.1038/cddis.2012.99, ISSN: 2041-4889. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22874998., 2012.

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 [print-electronic]. 2012 May; 213(2): 173-82. PMID: 22393245, PII: JOE-11-0474, DOI: 10.1530/JOE-11-0474, ISSN: 1479-6805. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22393245., 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 [print-electronic]. 2012 Aug; 32(16): 3190-202. PMID: 22665497, PMCID: PMC3434546, PII: MCB.00159-12, DOI: 10.1128/MCB.00159-12, ISSN: 1098-5549. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22665497., 2012.

Franco OE, Jiang M, Strand DW, Peacock J, Fernandez S, Jackson RS, Revelo MP, Bhowmick NA, Hayward SW. Altered TGF-ß signaling in a subpopulation of human stromal cells promotes prostatic carcinogenesis. Cancer Res [print-electronic]. 2011 Feb 2/15/2011; 71(4): 1272-81. PMID: 21303979, PMCID: PMC3076790, PII: 0008-5472.CAN-10-3142, DOI: 10.1158/0008-5472.CAN-10-3142, ISSN: 1538-7445. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21303979., 2011.

Jiang M. Interplay between autophagy and metabolism in Ras mutation-induced tumorigenesis. Asian J. Androl [print-electronic]. 2011 Jul; 13(4): 610-1. PMID: 21499280, PMCID: PMC3739627, PII: aja201131, DOI: 10.1038/aja.2011.31, ISSN: 1745-7262. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21499280., 2011.

Jiang M, Strand DW, Franco OE, Clark PE, Hayward SW. PPAR¿: a molecular link between systemic metabolic disease and benign prostate hyperplasia. Differentiation [print-electronic]. 2011 Nov; 82(4-5): 220-36. PMID: 21645960, PMCID: PMC3174339, PII: S0301-4681(11)00098-3, DOI: 10.1016/j.diff.2011.05.008, ISSN: 1432-0436. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21645960., 2011.

Jiang M, Jerome WG, Hayward SW. Autophagy in nuclear receptor PPARgamma-deficient mouse prostatic carcinogenesis. Autophagy [print-electronic]. 2010 Jan; 6(1): 175-6. PMID: 20009560, PII: 10700, ISSN: 1554-8635. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20009560., 2010.

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