Prof. James Y. Yang,  BS in Microbiology (1982), Xiamen University; PhD in Biochemistry/Molecular Biology (1994), University of Houston, Texas; 1982 -1988, Assistant Engineer, Guangzhou Institute of Microbiology; 1996-1998; NIH Postdoctoral Fellow/Associate Research Scientist (1994-1998), Department of Biochemistry/Ophthalmology, Columbia University, New York; 1998-2005, Research Assistant Professor/Research Officer , Institute of Molecular Biology/Department of Physiology, The University of Hong Kong; 2006 – present, Professor, Xiamen University.

 主要研究领域(Research interests)

AKR 超家族是在细胞代谢、免疫/炎症应答、渗透调控、细胞解毒、激素合成、生殖发育与代谢调控等生命活动中扮演着重要角色的一大组蛋白酶。研究已表明该家族的多个成员与糖尿病和糖尿病并发症, 肥胖和代谢综合征以及心血管病、肝癌/肝炎、前列腺癌等人类重大疾病的发生或演进密切相关。本课题组通过对细胞模型和转基因/基因剔除基因工程动物模型的研究, 来试图阐释AKR家族成员及相关基因在代谢疾病和癌症的发生与发展中的作用及其分子细胞机制, 探讨可能的预防与治疗的方法与手段。目前研究的重点包括醛糖还原酶(AR, AKR1B1)、醛糖还原酶类似酶-1 (ARL-1, AKR1B10)、黄曲霉毒素醛还原酶 (AKR7A)、渗透调控转录因子NFAT5/TonEBP/OREB、血清-糖皮质激素诱导激酶 (SGK)等。我们最近发现, AR可通过调节ERK-MAPK信号转导来改变肝代谢性核受体PPARa 的磷酸化程度和活性,进而影响细胞糖脂内稳定。醛糖还原酶介导的这一PPARa调控的新机制的发现对糖尿病与糖尿病并发症的病理发生机制的进一步阐明有着重要的意义, 它同时为相关代谢疾病的预防与治疗提供了新的理论基础和思路。

The aldo-keto reductase (AKR) superfamily consists of a large group of enzymes that play important roles in cellular metabolism, inflammatory responses, osmoregulation, endobiotic and xenobiotic detoxification, hormone synthesis and action, metabolic regulation and reproduction etc. Many of the AKR superfamily members have been shown to contribute to the development and progression of important human diseases including diabetes and diabetic complications, obesity, metabolic syndrome, cardiovascular disease, hepatitis, liver cancer and prostate cancer. Utilizing both cell cultures and genetically-manipulated mouse models, research in this lab is focused on the elucidation of the roles of AKR members and related proteins in the pathogenesis of relevant human diseases, with the long-term goals of better-understanding the underlying molecular and cellular mechanisms and the development of novel therapeutic strategies for related diseases.

科研基金 (Research funding)

1.)      国家自然科学基金, 项目号30770490, 多元醇糖代谢支路在糖尿病肾病发生发展中的作用, 主持, ¥350,000, Jan, 2008-Dec. 2010

2.)      厦门大学985计划项目经费, 代谢性疾病的分子细胞机理研究平台建设, 主持, ¥3,000,000, Mar. 2006 –  Mar. 2009

3.)      Pfizer Global Research and Development grant (主持), The polyol pathway in diabetic nephropathy. HK$ 273,000, May 2004 – April 2005

4.)      Hong Kong Research Grant Council grant (主持), The polyol pathway as a thrifty pathway promoting energy storage. HK$1,387,800, Sept. 2003 – Aug. 2006

5.)      Hong Kong Research Grant Council grant (主持), The role of osmotic response element binding protein in osmoregulation. HK$800,400, Sep 2000 -Aug 2003

6.)      RGC Direct Allocation (主持), The polyol pathway in agouti-induced lipogenesis and obesity. HK$120,000, Aug. 2002 – Sept. 2003

近期论文与奖项(Publications and awards, *Corresponding) 

1.      Guo,Z.S., Li,Q., Bartlett,D.L., Yang,J.Y., and Fang,B.L. 2008. Gene transfer: the challenge of regulated gene expression. Trends Mol.Med. (In press).

2.      Qiu,L., Wu,X., Chau,J.F., Szeto,I.Y.Y., Tam,W.Y., Guo,Z.S, Chung,S.K., Oates,P.J., Chung,S.S.M., and Yang,J.Y. * 2008. Aldose reductase regulates hepatic peroxisome proliferator-activated receptor a phosphorylation  and activity to impact lipid homeostasis. J.Biol.Chem. 283:17175-17183.

3.      Yang,J.Y. *, Gao,D.M., and Guo,Z.S. 2008. [A few aspects of the biology of Agouti and Agouti-related proteins]. Chinese J.Zoology (In press).

4.      Yang,J.Y. *, Tam,W.Y., Tam,S., Guo,H., Wu,X., Li,G., Chau,J.F., Klein,J.D., Chung,S.K., Sands,J.M. et al. 2006. Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism. Am.J.Physiol Renal Physiol 291:F186-F195.

5.      Wang,Y., Ko,B.C., Yang,J.Y*., Lam,T.T., Jiang,Z., Zhang,J., Chung,S.K., and Chung,S.S. 2005. Transgenic mice expressing dominant-negative osmotic-response element-binding protein (OREBP) in lens exhibit fiber cell elongation defect associated with increased DNA breaks. J.Biol.Chem. 280:19986-19991.

6.      Lam,A.K.M., Ko,B.C.B., Tam,S., Morris,R., Yang,J.Y., Chung,S.K., and Chung,S.S.M. 2004. Osmotic response element binding protein (OREBP) is an essential regulator of urine concentrating mechanism. J.Biol.Chem. 279:48048-48054.

7.      Kuang,K., Li,Y., Wen,Q., Wang,Z., Li,J., Yang,Y., Iserovich,P., Reinach,P.S., Sparrow,J., Diecke,F.P. et al. 2001. Corneal endothelial NKCC: molecular identification, location, and contribution to fluid transport. Am.J.Physiol Cell Physiol 280:C491-C499.

8.      Kelz,M.B., Kuszak,J.R., Yang,Y., Ma,W., Steffen,C., Al Ghoul,K., Zhang,Y.J., Chen,J., Nestler,E.J., and Spector,A. 2000. DeltaFosB-induced cataract. Invest Ophthalmol.Vis.Sci. 41:3523-3538.

9.      Ko,B.C., Turck,C.W., Lee,K.W., Yang,Y., and Chung,S.S. 2000. Purification, identification, and characterization of an osmotic response element binding protein. Biochem.Biophys.Res.Commun. 270:52-61.

10.  第三届世界肾科学大会APSN最佳论文奖, 新加坡, 2005(APSN Best Abstract Award, 3^rd World Congress on Nephrology, Singapore, 2005) Tam, W.Y., J.Y. Yang*, G.H. Li, X.C. Wu, F.L. Chau, S. Tam, J. D. Klein, S.K. Chung, J. M. Sands and S.S.M. Chung (2005) Aldose reductase protects renal collecting tubule epithelial cells from hyperosmolarity-induced DNA damage.

11.  国际肾科学学会2004肾病防治大会最佳论文奖, 香港,2004 (ISN Best Abstract Award, the International Society of Nephrology 2004 Conference on Prevention of Progression of Renal Disease. Hong Kong). Yang, J.Y. *, H. Guo, X.C. Wu, F.L. Chau, S. Tam, S.K. Chung and S.S.M. Chung (2004) Kidney local deficiency of aldose reductase is sufficient to cause polyuria and polydipsia in mice.

实验室成员 (Lab members)

v      郭宗圣博士, 闽江学者讲座教授

v      邱龙新副教授 (龙岩学院, 在职博士生)

v      纪慈数, 实验师 (XMULAC)

v      刘俊, 硕士, 助理实验师 (XMULAC)

v      于水舟, 硕士, 助理实验师 (XMULAC)

联系方式

    电邮：jamesyang@xmu.edu.cn

   电话和传真：86592-2187230