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

Profile

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. 

Publications

The following timeline graph is generated from all co-authored publications.

1. ALCAM/CD166 is a TGF-β-responsive marker and functional regulator of prostate cancer metastasis to bone. 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 (2014) Cancer Res 74(5): 1404-15
   › Primary publication · 24385212 (PubMed) · PMC4149913 (PubMed Central)
2. SPARCL1 suppresses metastasis in prostate cancer. 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 (2013) Mol Oncol 7(6): 1019-30
   › Primary publication · 23916135 (PubMed) · PMC3838491 (PubMed Central)
3. Deficiency in metabolic regulators PPARγ and PTEN cooperates to drive keratinizing squamous metaplasia in novel models of human tissue regeneration. 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 (2013) Am J Pathol 182(2): 449-59
   › Primary publication · 23219716 (PubMed) · PMC3562729 (PubMed Central)
4. Cathepsin D acts as an essential mediator to promote malignancy of benign prostatic epithelium. Pruitt FL, He Y, Franco OE, Jiang M, Cates JM, Hayward SW (2013) Prostate 73(5): 476-88
   › Primary publication · 22996917 (PubMed) · PMC3594371 (PubMed Central)
5. PPARγ isoforms differentially regulate metabolic networks to mediate mouse prostatic epithelial differentiation. Strand DW, Jiang M, Murphy TA, Yi Y, Konvinse KC, Franco OE, Wang Y, Young JD, Hayward SW (2012) Cell Death Dis : e361
   › Primary publication · 22874998 (PubMed) · PMC3434663 (PubMed Central)
6. The stress response mediator ATF3 represses androgen signaling by binding the androgen receptor. Wang H, Jiang M, Cui H, Chen M, Buttyan R, Hayward SW, Hai T, Wang Z, Yan C (2012) Mol Cell Biol 32(16): 3190-202
   › Primary publication · 22665497 (PubMed) · PMC3434546 (PubMed Central)
7. Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells. Lee SO, Tian J, Huang CK, Ma Z, Lai KP, Hsiao H, Jiang M, Yeh S, Chang C (2012) J Endocrinol 213(2): 173-82
   › Primary publication · 22393245 (PubMed)
8. PPARγ: a molecular link between systemic metabolic disease and benign prostate hyperplasia. Jiang M, Strand DW, Franco OE, Clark PE, Hayward SW (2011) Differentiation 82(4-5): 220-36
   › Primary publication · 21645960 (PubMed) · PMC3174339 (PubMed Central)
9. Spontaneous immortalization of human dermal microvascular endothelial cells. Jiang M, Min Y, Debusk L, Fernandez S, Strand DW, Hayward SW, Lin PC (2010) World J Stem Cells 2(5): 114-20
   › Primary publication · 21607128 (PubMed) · PMC3097930 (PubMed Central)
10. Interplay between autophagy and metabolism in Ras mutation-induced tumorigenesis. Jiang M (2011) Asian J Androl 13(4): 610-1
    › Primary publication · 21499280 (PubMed) · PMC3739627 (PubMed Central)
11. Altered TGF-β signaling in a subpopulation of human stromal cells promotes prostatic carcinogenesis. Franco OE, Jiang M, Strand DW, Peacock J, Fernandez S, Jackson RS, Revelo MP, Bhowmick NA, Hayward SW (2011) Cancer Res 71(4): 1272-81
    › Primary publication · 21303979 (PubMed) · PMC3076790 (PubMed Central)
12. Functional remodeling of benign human prostatic tissues in vivo by spontaneously immortalized progenitor and intermediate cells. Jiang M, Strand DW, Fernandez S, He Y, Yi Y, Birbach A, Qiu Q, Schmid J, Tang DG, Hayward SW (2010) Stem Cells 28(2): 344-56
    › Primary publication · 20020426 (PubMed) · PMC2962907 (PubMed Central)
13. Autophagy in nuclear receptor PPARgamma-deficient mouse prostatic carcinogenesis. Jiang M, Jerome WG, Hayward SW (2010) Autophagy 6(1): 175-6
    › Primary publication · 20009560 (PubMed)
14. Disruption of PPARgamma signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy. 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 (2010) Cell Death Differ 17(3): 469-81
    › Primary publication · 19834493 (PubMed) · PMC2821953 (PubMed Central)
15. Methodologies in assaying prostate cancer stem cells. Li H, Jiang M, Honorio S, Patrawala L, Jeter CR, Calhoun-Davis T, Hayward SW, Tang DG (2009) Methods Mol Biol : 85-138
    › Primary publication · 19582423 (PubMed)
16. Activation of beta-Catenin in mouse prostate causes HGPIN and continuous prostate growth after castration. Yu X, Wang Y, Jiang M, Bierie B, Roy-Burman P, Shen MM, Taketo MM, Wills M, Matusik RJ (2009) Prostate 69(3): 249-62
    › Primary publication · 18991257 (PubMed) · PMC4437562 (PubMed Central)
17. Critical and distinct roles of p16 and telomerase in regulating the proliferative life span of normal human prostate epithelial progenitor cells. 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 (2008) J Biol Chem 283(41): 27957-27972
    › Primary publication · 18662989 (PubMed) · PMC2562067 (PubMed Central)
18. Temporally controlled ablation of PTEN in adult mouse prostate epithelium generates a model of invasive prostatic adenocarcinoma. Ratnacaram CK, Teletin M, Jiang M, Meng X, Chambon P, Metzger D (2008) Proc Natl Acad Sci U S A 105(7): 2521-6
    › Primary publication · 18268330 (PubMed) · PMC2268169 (PubMed Central)
19. Tissue-specific consequences of cyclin D1 overexpression in prostate cancer progression. He Y, Franco OE, Jiang M, Williams K, Love HD, Coleman IM, Nelson PS, Hayward SW (2007) Cancer Res 67(17): 8188-97
    › Primary publication · 17804732 (PubMed)
20. Malignant transformation of DMBA/TPA-induced papillomas and nevi in the skin of mice selectively lacking retinoid-X-receptor alpha in epidermal keratinocytes. 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 (2007) J Invest Dermatol 127(5): 1250-60
    › Primary publication · 17301838 (PubMed)
21. Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation. 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 (2005) Development 132(15): 3431-43
    › Primary publication · 15987773 (PubMed)
22. Functional role of RXRs and PPARgamma in mature adipocytes. Metzger D, Imai T, Jiang M, Takukawa R, Desvergne B, Wahli W, Chambon P (2005) Prostaglandins Leukot Essent Fatty Acids 73(1): 51-8
    › Primary publication · 15936932 (PubMed)
23. Approaches to understanding the importance and clinical implications of peroxisome proliferator-activated receptor gamma (PPARgamma) signaling in prostate cancer. Jiang M, Shappell SB, Hayward SW (2004) J Cell Biochem 91(3): 513-27
    › Primary publication · 14755682 (PubMed)
24. [PTEN expression and its significance in human primary hepatocellular carcinoma]. Wan XW, Wang HY, Jiang M, He YQ, Liu SQ, Cao HF, Qiu XH, Tang L, Wu MC (2003) Zhonghua Gan Zang Bing Za Zhi 11(8): 490-2
    › Primary publication · 12939185 (PubMed)
25. The alteration of PTEN tumor suppressor expression and its association with the histopathological features of human primary hepatocellular carcinoma. Wan XW, Jiang M, Cao HF, He YQ, Liu SQ, Qiu XH, Wu MC, Wang HY (2003) J Cancer Res Clin Oncol 129(2): 100-6
    › Primary publication · 12669234 (PubMed)
26. p53 independent G1 arrest and apoptosis induced by adriamycin. Shao Z, Jiang M, Yu L, Han Q, Shen Z (1997) Chin Med Sci J 12(2): 71-5
    › Primary publication · 11324502 (PubMed)
27. Selective ablation of retinoid X receptor alpha in hepatocytes impairs their lifespan and regenerative capacity. Imai T, Jiang M, Kastner P, Chambon P, Metzger D (2001) Proc Natl Acad Sci U S A 98(8): 4581-6
    › Primary publication · 11287642 (PubMed) · PMC31877 (PubMed Central)
28. Estrogen receptor-negative breast cancer cells transfected with estrogen receptor exhibit decreased tumour progression and sensitivity to growth inhibition by estrogen. Shao Z, Jiang M, Yu L, Han Q, Shen Z (1997) Chin Med Sci J 12(1): 11-4
    › Primary publication · 11243092 (PubMed)
29. 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. Imai T, Jiang M, Chambon P, Metzger D (2001) Proc Natl Acad Sci U S A 98(1): 224-8
    › Primary publication · 11134524 (PubMed) · PMC14572 (PubMed Central)
30. [WAF1/CIP1/p21 gene in wild type p53 and mutant p53 human breast cancer cell lines in relation to its cytobiological features]. Jiang M, Shao Z, Wu J (1998) Zhonghua Zhong Liu Za Zhi 20(3): 181-4
    › Primary publication · 10921001 (PubMed)
31. [In situ DNA labeling apoptosis in breast cancer as related to prognosis]. Wu J, Shao Z, Jiang M (1997) Zhonghua Zhong Liu Za Zhi 19(2): 100-2
    › Primary publication · 10743070 (PubMed)
32. [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]. Jiang M, Shao Z, Zhang Y (1997) Zhonghua Bing Li Xue Za Zhi 26(6): 327-30
    › Primary publication · 10374318 (PubMed)
33. Prognostic role of p27Kip1 and apoptosis in human breast cancer. Wu J, Shen ZZ, Lu JS, Jiang M, Han QX, Fontana JA, Barsky SH, Shao ZM (1999) Br J Cancer 79(9-10): 1572-8
    › Primary publication · 10188908 (PubMed) · PMC2362719 (PubMed Central)
34. Inhibition of spontaneous apoptosis in human breast cancer. Shao Z, Jiang M, Wu J, Yu L, Han Q, Zhang T, Shen Z (1996) Chin Med Sci J 11(4): 200-3
    › Primary publication · 9387382 (PubMed)
35. p21/waf1/cip1 and mdm-2 expression in breast carcinoma patients as related to prognosis. Jiang M, Shao ZM, Wu J, Lu JS, Yu LM, Yuan JD, Han QX, Shen ZZ, Fontana JA (1997) Int J Cancer 74(5): 529-34
    › Primary publication · 9355976 (PubMed)

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