Ming Jiang, M.D., Ph.D.

Research Associate Professor


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Faculty Appointments
Research Associate Professor of Medicine
Ph.D., Fudan University, Shanghai, ChinaM.S., Nantong Medical College, Jiangsu, ChinaM.D., Nantong Medical College, Jiangsu, China
Office Address
Division of Epidemiology, Suite 334
2525 West End Avenue, Nashville, TN
Nashville, TN 37203-1738
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
Research Keywords
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.
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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. 2010 Oct 10/26/2010; 2(5): 114-20. PMID: 21607128, PMCID: PMC3097930, DOI: 10.4252/wjsc.v2.i5.114, ISSN: 1948-0210.

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 [print-electronic]. 2010 Mar; 17(3): 469-81. PMID: 19834493, PMCID: PMC2821953, PII: cdd2009148, DOI: 10.1038/cdd.2009.148, ISSN: 1476-5403.

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. 2010 Feb; 28(2): 344-56. PMID: 20020426, PMCID: PMC2962907, DOI: 10.1002/stem.284, ISSN: 1549-4918.

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.

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. 2009 Feb 2/15/2009; 69(3): 249-62. PMID: 18991257, PMCID: PMC4437562, DOI: 10.1002/pros.20877, ISSN: 1097-0045.

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. 2009; 568: 85-138. PMID: 19582423, DOI: 10.1007/978-1-59745-280-9_7, ISSN: 1064-3745.

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 [print-electronic]. 2008 Oct 10/10/2008; 283(41): 27957-72. PMID: 18662989, PMCID: PMC2562067, PII: M803467200, DOI: 10.1074/jbc.M803467200, ISSN: 0021-9258.

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 [print-electronic]. 2008 Feb 2/19/2008; 105(7): 2521-6. PMID: 18268330, PMCID: PMC2268169, PII: 0712021105, DOI: 10.1073/pnas.0712021105, ISSN: 1091-6490.

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. 2007 Sep 9/1/2007; 67(17): 8188-97. PMID: 17804732, PII: 67/17/8188, DOI: 10.1158/0008-5472.CAN-07-0418, ISSN: 0008-5472.

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 [print-electronic]. 2007 May; 127(5): 1250-60. PMID: 17301838, PII: 5700672, DOI: 10.1038/sj.jid.5700672, ISSN: 1523-1747.

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 [print-electronic]. 2005 Aug; 132(15): 3431-43. PMID: 15987773, PII: dev.01917, DOI: 10.1242/dev.01917, ISSN: 0950-1991.

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. 2005 Jul; 73(1): 51-8. PMID: 15936932, PII: S0952-3278(05)00059-1, DOI: 10.1016/j.plefa.2005.04.007, ISSN: 0952-3278.

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. 2004 Feb 2/15/2004; 91(3): 513-27. PMID: 14755682, DOI: 10.1002/jcb.10770, ISSN: 0730-2312.

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. 2003 Aug; 11(8): 490-2. PMID: 12939185, ISSN: 1007-3418.

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 [print-electronic]. 2003 Feb; 129(2): 100-6. PMID: 12669234, DOI: 10.1007/s00432-002-0410-x, ISSN: 0171-5216.

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 [print-electronic]. 2001 Apr 4/10/2001; 98(8): 4581-6. PMID: 11287642, PMCID: PMC31877, PII: 071056098, DOI: 10.1073/pnas.071056098, ISSN: 0027-8424.

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. 2001 Jan 1/2/2001; 98(1): 224-8. PMID: 11134524, PMCID: PMC14572, PII: 011528898, DOI: 10.1073/pnas.011528898, ISSN: 0027-8424.

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. 1999 Mar; 79(9-10): 1572-8. PMID: 10188908, PMCID: PMC2362719, DOI: 10.1038/sj.bjc.6690250, ISSN: 0007-0920.

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. 1998 May; 20(3): 181-4. PMID: 10921001, ISSN: 0253-3766.

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. 1997 Dec; 26(6): 327-30. PMID: 10374318, ISSN: 0529-5807.

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. 1997 Oct 10/21/1997; 74(5): 529-34. PMID: 9355976, PII: 10.1002/(SICI)1097-0215(19971021)74:5<529::AID-IJC9>3.0.CO;2-5, ISSN: 0020-7136.

Shao Z, Jiang M, Yu L, Han Q, Shen Z. P53 independent G1 arrest and apoptosis induced by adriamycin. Chin. Med. Sci. J. 1997 Jun; 12(2): 71-5. PMID: 11324502, ISSN: 1001-9294.

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. 1997 Mar; 12(1): 11-4. PMID: 11243092, ISSN: 1001-9294.

Wu J, Shao Z, Jiang M. [In situ DNA labeling apoptosis in breast cancer as related to prognosis]. Zhonghua Zhong Liu Za Zhi. 1997 Mar; 19(2): 100-2. PMID: 10743070, ISSN: 0253-3766.

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. 1996 Dec; 11(4): 200-3. PMID: 9387382, ISSN: 1001-9294.