韓曉

韓曉，男，博士，特聘教授，博士生導師，江蘇省人類功能基因組學重點實驗室主任。1986年畢業於武漢同濟醫科大學六年制醫學本科，同年考取同濟醫科大學分子病毒學與免疫學專業碩士研究生，碩士畢業后留校任教。於1991年公派赴聯邦德國維爾茨堡大學攻讀生物免疫與病毒學博士學位，1994年獲博士學位后在德國明斯特大學分子醫學所從事細胞因子、金屬蛋白酶和糖尿病的博士后研究。1996年赴美國洛衫磯City of Hope National Medical Center糖尿病研究中心從事分子免疫學與糖尿病等的研究。曾獲美國國際青少年糖尿病研究基金會資助（JDRF），2003年元月回國定居，被南京醫科大學聘為教授、江蘇省人類功能基因組學重點實驗室學科帶頭人。

糖尿病發病機制。

利用先進的分子生物學和生物化學技術，發現花生四烯酸-前列腺素生成信號轉導途徑中，12-脂氧化酶的代謝產物12-HETE其有誘導前列腺素合成的關鍵酶--環加氧酶-2（COX-2）基因轉錄和表達的作用，而用12-脂氧化酶的抑製劑-咖啡酸類物質，可以抑制12-HETE的合成，從而減弱COX-2基因的轉錄和表達，進而減少前列腺素的合成。鑒於前列腺素有抑制β-細胞分泌胰島素的作用，所以，這一新的信號轉導通路的發現，有助於進一步揭示1、2型糖尿病對胰島β-細胞發生功能障礙的機理。發現了基質金屬蛋白酶組織抑制因子-1（TIMP-1）對胰島β-細胞的凋亡具有保護作用，並藉助分子生物學和細胞生物學技術，進一步研究了胰島β-細胞發生凋亡的機理，揭示了核轉錄因子NF-KB與β-細胞發生凋亡之間的關係，為轉基因胰島移植及1型糖尿病的基因治療提供了新的新的思路。已在多種國際著名學術期刊上發表學術論文，且在COX-2基因調控的信號轉導方面獲一項美國專利。

獲得一項美國專利和二項中國專利。獲江蘇省科技進步二等獎一項（排名第一）；江蘇省有突出貢獻中青年專家，江蘇省“333”突出貢獻獎。

1.Wang Y, Lin H, Hao N, Zhu Z, Wang D, Li Y, Chen H, Zhu Y, Han X*. Forkhead box O1 mediates defects in palmitate-induced insulin granule exocytosis by downregulation of calcium/calmodulin-dependent serine protein kinase expression in INS-1 cells.Diabetologia. 2015 Mar 22. [Epub ahead of print]

2.Qiao N, Xu C, Zhu YX, Cao Y, Liu DC, Han X*. Ets-1 as an early response gene against hypoxia-induced apoptosis in pancreatic β-cells. Cell Death Dis. 2015 Feb 19;6:e1650.

3.Nie J, Liu X, Lilley BN, Zhang H, Pan YA, Kimball SR, Zhang J, Zhang W, Wang L, Jefferson LS, Sanes JR, Han X*, Shi Y*. SAD-A kinase controls islet β-cell size and function as a mediator of mTORC1 signaling. Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13857-62

4.Zhu Y, You W, Wang H, Li Y, Qiao N, Shi Y, Zhang C, Bleich D, Han X*. MicroRNA-24/MODY Gene Regulatory Pathway Mediates Pancreatic Beta-Cell Dysfunction. Diabetes. 2013 Sep;62(9):3194-206.

5.Nie J, Lilley BN, Pan YA, Faruque O, Liu X, Zhang W, Sanes JR, Han X*, Shi Y*. SAD-A Potentiates Glucose-Stimulated Insulin Secretion as a Mediator of Glucagon-Like Peptide 1 Response in Pancreatic β Cells. Mol Cell Biol. 2013 Jul;33(13):2527-34.

6.Lin HY, Yin Y, Zhang JX, Xuan H, Zheng Y, Zhan SS, Zhu YX, Han X*, Identification of direct forkhead box O1 targets involved in palmitate-induced apoptosis in clonal insulin-secreting cells using chromatin immunoprecipitation coupled to DNA selection and ligation, Diabetologia. 2012 Oct;55(10):2703-12..

7.Nie J, Sun C, Faruque O, Ye G, Li J, Liang Q, Chang Z, Yang W, Han X*, Shi Y*, Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic β-cells, J Biol Chem. 2012 Jul 27;287(31):26435-44.

8.Meng ZX, Yin Y, Lv JH, Sha M, Lin Y, Gao L, Zhu YX, Sun YJ, Han X*. Aberrant activation of liver X receptors impairs pancreatic beta cell function through upregulation of Sterol regulatory element-binding protein 1c in mouse islets and rodent cell lines. Diabetologia, 2012 Jun;55(6):1733-44. Epub 2012 Mar 14.6.973

9.Li W, Chen Z, Gong FR, Zong Y, Chen K, Li DM, Yin H, Duan WM, Miao Y, Tao M, Han X*, Xu ZK*. Growth of the pancreatic cancer cell line PANC-1 is inhibited by protein phosphatase 2A inhibitors through overactivation of the c-Jun N-terminal kinase pathway. Eur J Cancer. 2011 Nov; 47(17):2654-64. Epub 2011 Sep 28. 4.944

10.Shu T, Zhu Y, Wang H, Lin Y, Ma Z, Han X*. AGEs Decrease Insulin Synthesis in Pancreatic β-Cell by Repressing Pdx-1 Protein Expression at the Post-Translational Level. PLoS One. 2011 Apr 18;6(4): e18782. 4.351

11.Chen F, Zhu Y, Tang X, Sun Y, Jia W, Sun Y, Han X*. Dynamic Regulation of PDX-1 and FoxO1 Expression by FoxA2 in Dexamethasone-Induced Pancreatic {beta}-cells Dysfunction. Endocrinology. 2011 May;152(5):1779-88. Epub 2011 Mar 8. 4.752

12.Li W, Chen Z, Zong Y, Gong F, Zhu Y, Zhu Y, Lv J, Zhang J, Xie L, Sun Y, Miao Y, Tao M, Han X*, Xu Z*. PP2A inhibitors induceapoptosis in pancreatic cancer cell line PANC-1 through persistent phosphorylation of IKKα and sustained activation of the NF-κB pathway. Cancer Lett. 2011 May 28;304(2):117-27. Epub 2011 Mar 3. 3.741

13.Shen H, Xu W, Luo W, Zhou L, Yong W, Chen F, Wu C, Chen Q, Han X*. Upregulation of mdr1 gene is related to activation of the MAPK/ERK signal transduction pathway and YB-1 nuclear translocation in B-cell lymphoma. Exp Hematol. 2011 May;39(5):558-69. Epub 2011 Feb 24. 3.106

14.Zhu Y, Shu T, Lin Y, Wang H, Yang J, Shi Y, Han X*. Inhibition of the receptor for advanced glycation endproducts (RAGE) protects pancreatic β-cells. Biochem Biophys Res Commun. 2011 Jan 7; 404(1):159-65. 2.548

15.Lin Y, Tang X, Zhu Y, Shu T, Han X*. Identification of PARP-1 as one of thetranscription factors binding to the repressor element in the promoter region of COX-2. Arch Biochem Biophys. 2011 Jan 1; 505(1):123-9. 3.046

16.Guo J, Zhu JX, Deng XH, Hu XH, Zhao J, Sun YJ, Han X*. Palmitate-induced inhibition of insulin gene expression in rat islet β-cells involves the ceramide transport protein. Cell Physiol Biochem. 2010;26(4-5):717-28. 3.563

17.Li W, Xie L, Chen Z, Zhu Y, Sun Y, Miao Y, Xu Z*, Han X*. Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis. Cancer Sci. 2010 May;101(5):1226-33. 3.771

18.Guo J, Qian Y, Xi X, Hu X, Zhu J, Han X*. Blockage of ceramide metabolism exacerbates palmitate inhibition of pro-insulin gene expression in pancreatic beta-cells. Mol Cell Biochem. 2010 May;338(1-2):283-90. 1.896

19.Meng Z, Lv J, Luo Y, Lin Y, Zhu Y, Nie J, Yang T, Sun Y, Han X*. Forkhead Box O1/Pancreatic and Duodenal Homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. Endocrinology. 2009 Dec; 150(12):5284-93. 4.945

20.Zhou X, Zheng M, Chen F, Zhu Y, Yong W, Lin H, Sun Y, Han X*.Gefitinib inhibits the proliferation of pancreatic cancer cells via cell cycle arrest. Anat Rec (Hoboken). 2009 Aug; 292(8):1122-7. 1.569

21.Zhang XF, Yong W, Lv JH, Zhu YX, Zhang JJ, Chen F, Zhang RH, Yang T, Sun YJ, Han X*. Inhibition of forkhead box O1 protects pancreatic beta-cells against dexamethasone-induced dysfunction. Endocrinology. 2009 Sep; 150(9):4065-73. 4.945

22.Xia W, Zhao T, Lv JH, Xu S, Shi J, Wang S, Han X*, Sun YJ*. Celecoxib enhanced the sensitivity of cancer cells to anticancer drugs by inhibition of the expression of P-glycoprotein through a COX-2-independent Manner. J Cell Biochem. 2009 Sep 1;108(1):181-94. 3.54

23.Yin Y, Wang S, Sun Y, Matt Y, Colburn NH, Shu Y*, Han X*. JNK/AP-1 pathway is involved in tumor necrosis factor-alpha induced expression of vascular endothelial growth factor in MCF7 cells. Biomed Pharmacother. 2009 Jul; 63(6):429-35. 2.198

24.Meng ZX, Nie J, Ling JJ, Sun JX, Zhu YX, Gao L, Lv JH, Zhu DY, Sun YJ, Han X*. Activation of liver X receptors inhibits pancreatic islet beta cell proliferation through cell cycle arrest. Diabetologia. 2009 Jan;52(1):125-35. 6.418

25.Yang X, Lin L, Zhang X, Ji Y, Lv J, Zhu Y, Yin Y, Sun Y, Han X*. Identification of a novel repressor element in the cyclo-oxygenase-2 promoter and its nuclear binding protein. Clin Exp Pharmacol Physiol. 2008 Oct;35(10):1204-8. 2.04

26.Zhu J, Yong W, Wu X, Yu Y, Lv J, Liu C, Mao X, Zhu Y, Xu K, Han X*, Liu C*. Anti-inflammatory effect of resveratrol on TNF-alpha-induced MCP-1 expression in adipocytes. Biochem Biophys Res Commun. 2008 May 2; 369(2):471-7. 2.75

27.Ma C, Zhang JJ, Durrin KL. Lv JH, Zhu D, Han X*, and Sun Y*.（2007). The BCL2 major breakpoint region (mbr) regulates gene expression. Oncogene 26（18）2649-57 IF 6.440 co-corresponding author

徠28.Meng Z, Sun J, Ling J, Lv J, Zhu DY, Chen Q, Sun Y* and Han X*. (2006) Prostaglandin E2 regulates Foxo activity via the Akt pathway: implications for pancreatic islat beta-cell dysfunction. Diabetologia 49(12):2959-68 IF 5.337 corresponding author

29.Zhang JJ， Ma CY, Han X*, Durrin L, and Sun Y*. (2006). The BCL2 major breakpoint region (mbr) possesses transcriptional regulatory function. Gene 379：127-131. IF 2.69 *Co-corresponding author

30.Sun Y, Wang T, Yin Y, Xu S, Ma C, Han X* (2006). The behavior of SATB1, a MAR binding protein, in response to apoptosis stimulation. Cell Biology International. 30(3):244-247. IF 1.19 corresponding author

31.Wang Z, Lv JH, Zhang RH, ZyX, Sun Y, Zhu J, Han X*. (2006). Co-culture with fat cells induces insulin resistance in primary hepatocytes. BBRC 345 (3):976-83. IF 3.0 *corresponding author

32.Xu ZK, Chen NG, Ma CY, Meng ZX, Sun YJ, Han X*. (2006).Role of peroxisome proliferator-activated receptor gamma in glucose-induced insulin secretion. Acta Biochim. Biophys. Sin. 38(1):1-7. IF 0.5 corresponding author

3.Lin J, Sun Y, Zhu D, Chen Q and Han X*. (2005). Potential role of NO in modulation of COX-2 expression and PGE2 production in pancreatic β-cells. Acta Biochimica et Biophysica Sinica 37(2):139-146. IF 0.5 corresponding autho

34.Han X, Chen S, Sun Y, Jerry L. Nadler, and Bleich D. (2002). Induction of cyclooxygenase-2 (COX-2) gene in pancreatic beta cells by 12-lipoxygenase pathway product 12-hydroxyeicosatetraenoic acid (12-HETE). Molecular Endocrinology. 19: 2145-2154.

35.Han X, Sun Y, Stephen Scott, and David Bleich. (2001). Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) prevents cytokine-mediated dysfunction and cytotoxicity in pancreatic islets and b-cells. Diabetes. 50(5): 1047-55.

36.Han X, Lundberg P, Tanamachi B, Openshaw H, Longmate J, Cantin E.(2001) Gender influences herpes simplex virus type 1 infection in normal and gamma interferon-mutant mice. J Virol. Mar; 75(6):3048-52.