Jianping Ye, M.D.

Professor of Molecular Biology
Chief, Antioxidant and Gene Regulation Lab

Antioxidant and Gene Regulation Lab
(225) 763-3163
(225) 763-2525
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M.D., Beijing Medical University, Beijing, PR China, 1989, Medicine


1. IKK/NF-kB Signalling Pathway: I have been studying IKK/NF-kB signalling pathway since 1993. In the early studies, the research was focused on tumor immunity, such as NF-kB activities in tumor-baring mice, in the regulation of interferon gamma transcription, and in response to oxidative stress. Then, I conducted a systematic study of NF-kB in response to environmental factors including vanadium (1), glass fiber (2), silica (3), asbestos (4) and glucan (5). These studies suggest that NF-kB is the major transcription factor mediating the transcriptional activation of TNF-a and inflammatory genes in cellular response to the environmental factors. In order to control IKK/NF-kB activity, I explored variety of approaches including chemical antioxidants (1, 2, 6), herbal extract (7), tea extract (8), antisense oligonucleotide (9), and synthetic peptide (10) to inhibit NF-kB activity. In addition to IKK/NF-kB pathway, I also studied mitogen-activated proteins kinase (MAPK). The focus was on the role of MAPK pathway in the regulation of cytokine transcription and carcinogenesis (11-14).

2. Inflammation in obesity: In 2001, I joined the faculty of Pennington Biomedical Research Center and started investigation into inflamamtion in obesity. The research has two subjects: a) how inflammation leads to insulin resistance; b) why inflammation occurs in obesity. My group first demonstrated that that: (a) NF-kB is activated in adipose tissue by hypoxia in obesity; (b) IKK was able to phosphorylate IRS-1 directly or indirectly by activating S6K1; (c) aspirin was able to inhibit multiple IRS-1 serine kinases including IKK, JNK, Akt, and mTOR in the regulation of insulin sensitivity; (d) NF-kB inhibits the transcriptional activity of PPARg through exchange of nuclear corepressor. These observations suggest that IKK contributes to insulin resistance by targeting IRS-1 and PPARg.

We were among the first to report that FFAs and hypoxia were able to activate IKK/NF-kB in adipsoe tissue in obesity. These observations lead to a hypothesis that FFAs and adipose tissue hypoxia contribute to chronic inflammation in obesity through activation of IKK/NF-kB pathway. Regarding how hypoxia reguglates adipose tissue function, we reported that hypoxia may act directly on adipocyets to induce lipolysis, apoptosis and necrosis.

3. Botanical study: My study in botanicals began in 1989 when I worked on the immune suppression effect of Chinese herbal medicine in the Beijing University. Then, I made an effort investigating the cancer prevention by herbs and tea extracts. The results suggest that herbal tetrandrine or tea extract (epigallocatechin-3-gallate, EGCG) are able to inhibit activation of nuclear factors NF-kB and AP-1. Additionally, my study suggests that mushroom extract (arenediazonium ions) is able to activate MAPKs including ERK, JNK and p38. Now, we are studying herbs and its extracts in the regulation of glucose and lipid metabolism. The herbs include berberine, ginger and Shilanhua.

For updated information, please visit my lab webpage at http://labs.pbrc.edu/generegulation/


Following are selected from >110 total peer-reviewed publications. For detail information, please visit my lab webpage: http://labs.pbrc.edu/generegulation/

Ye J, McGuinness OP: Inflammation during obesity is not all bad: Evidence from animal and human studies. Am J Physiol Endocrinol Metab 304:E466-E477, 2013

Hao Z, Zhao Z, Berthoud H-R, and Ye J. Development and Verification of a Mouse Model for Roux-en-Y Gastric Bypass Surgery with a Small Gastric Pouch. PLoS One 8:e52922, 2013.

Li H, Gao Z, Zhang J, Ye X, Xu A, Ye J, Jia W: Sodium Butyrate Stimulates Expression of Fibroblast Growth Factor 21 in Liver by Inhibition of Histone Deacetylase 3. Diabetes 61:797-806, 2012.

Xu F, Burk D, Gao Z, Yin J, Zhang X, Weng J, Ye J: Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1-/- Mice. Endocrinology 153:1706-1716, 2012.

Zhang J, Henagan TM, Gao Z, Ye J: Inhibition of glyceroneogenesis by Histone Deacetylase 3 Contributes to Lipodystrophy in Mice with Adipose Tissue Inflammation. Endocrinology 152 1829-1838, 2011.

Tang T, Zhang J, Yin J, Staszkiewicz J, Gawronska-Kozak B, Mynatt R, Martin RJ, Keenan M, Gao Z, Ye J: Uncoupling of Inflammation and Insulin Resistance by NF-kB in Transgenic Mice through Induction of Energy Expenditure. J Biol Chem 285:4637-4644, 2010

Xu F, Gao Z, Zhang J, Rivera CA, Yin J, Weng J, Ye J: Lack of SIRT1 (mammalian sirtuin 1) Activity Leads to Liver Steatosis in the SIRT1+/- Mice: A Role of Lipid Mobilization and Inflammation. Endocrinology 151 2504-2514, 2010

Gao Z, Yin J, J. Z, He Q, McGuinness OP, Ye J: Inactivation of NF-kB P50 Leads to Insulin Sensitization in liver through Post-Translational Inhibition of p70S6K. J. Biol. Chem. 284:18368-18376 2009

Yin J, Zuberi A, Gao Z, Liu D, Liu Z, Ye J: Shilianhua extract inhibits GSK-3{beta} and promotes glucose metabolism. Am J Physiol Endocrinol Metab 296:E1275-E1280, 2009

Gao Z, Yin J, Zhang J, Pope CR, Martin RJ, Cefalu WT, Ye J: Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice. Diabetes 58:1509-1517 2009

Ye J: Emerging Role of Adipose Tissue Hypoxia in Obesity and Insulin Resistance. International Journal of Obesity 33:54-66, 2009. (Review article)

Jun Yin, Zhanguo Gao, Qing He, and Jianping Ye. Potential role of hypoxia in obesity-induced disorder of glucose and lipid metabolism in adipose tissue. American Journal of Physiology-Endocrinology & Metabolism 296:E333-E342, 2009.

Zhang J, Gao Z, Yin J, Quon M, and Ye J: S6K Directly Phosphorylates IRS-1 on Ser270 to Promote Insulin Resistance in Response to TNF-a Signaling Through IKK2. Journal of Biological Chemistry 283:35375-35382, 2008.

Can Pang, Zhanguo Gao, Jun Yin, Jin Zhang, Weiping Jia and Jianping Ye: Macrophage Infiltration into Adipose Tissue May Promote Angiogenesis for Adipose Tissue Remodeling in Obesity. American Journal of Physiology-Endocrinology & Metabolism 295:313-322, 2008.

Jun Yin, Hanjie Zhang and Jianping Ye. Traditional Chinese Medicine in Treatment of Metabolic Syndrome. Endocrine, Metabolic and Immune Disorders-Drug Targets 8:99-111, 2008. (Review article)

Jun Yin, Zhanguo Gao, Dong Liu, Zhijun Liu and Ye J: Berberine Improves Glucose Metabolism through Induction of Glycolysis. American Journal of Physiology-Endocrinology & Metabolism. 294:E148-156, 2008.

Ye J, Gao Z, Yin J and He Q: Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. American Journal of Physiology-Endocrinology & Metabolism. 293:E1118-E1128, 2007.

Yan J, Gao Z, Yu G, Weng? J and Ye J: Nuclear Corepressor is Required for Phosphoenolpyruvate Carboxykinase Inhibition by TNF-a. Molecular Endocrinology 21:1630-1641, 2007.

Jianping Ye: Role of Insulin in the Pathogenesis of Free Fatty Acid-Induced Insulin Resistance in Skeletal Muscle. Endocrine, Metabolic and Immune Disorders-Drug Targets. 7:65-74, 2007. (review article)

Gao Z, Wang Z, Zhang X, Butler A, Zuberi A, Gawronska-Kozak B, Lefevre M, York D, Ravussin E, Berthoud HR, Cefalu WC and Ye J: Inactivation of PKCtheta Leads to Increased Susceptibility to Dietary Insulin Resistance in Mice. American Journal of Physiology-Endocrinology & Metabolism 292:E84-E91, 2007.

Gao Z, He Q, Peng B, Chiao P and Ye J: Regulation of Nuclear Translocation of HDAC3 by IkBalpha Involves in TNF-inhibition of PPARgamma Function. Journal of Biological Chemistry 281:4540-4547, 2006.

Gao Z, Chiao P, Zhang X, Zhang XH, Lazar MA, Seto E, Young HA and Ye J: Coactivators and Corepressors of NF-kB in IkB alpha Gene Promoter. Journal of Biological Chemistry 280:21091-21098, 2005.

Gao Z, Zhang X, Zuberi A, Hwang D, Quon MJ, Lefevre M, Ye J. Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes. Mol Endocrinol. 2004 Aug;18(8):2024-34. Epub 2004 May 13

Gao Z, Zuberi A, Quon MJ, Dong Z, Ye J. Aspirin inhibits serine phosphorylation of insulin receptor substrate 1 in tumor necrosis factor-treated cells through targeting multiple serine kinases. J Biol Chem. 2003 Jul 4;278(27):24944-50. Epub 2003 Apr 24

Lee JY, Ye J, Gao Z, Youn HS, Lee WH, Zhao L, Sizemore N, Hwang DH. Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids. J Biol Chem. 2003 Sep 26;278(39):37041-51. Epub 2003 Jul 15 ^ top