北京大學

余四旺：理學博士，副教授，碩士生導師

電話：（010）82801539

Email：swang_yu@bjmu.edu.cn

實驗室主頁：http://www.chemoprevention.net

通訊地址：北京市海淀區學院路38號藥學院308室 郵編：100191

1996年獲四川輕化工學院工學學士學位，2000年獲華中科技大學理學碩士學位；2003年獲北京大學藥學院理學博士學位,博士期間主要研究稀土元素生物效應的分子與細胞機理；2004年12月至2008年12月在美國新澤西州立大學從事博士后研究，主要研究天然植物成分用于腫瘤化學預防的動物模型與分子和細胞機理；2008年12月至今任北京大學藥學院副教授，主要從事預防藥學研究。近年來在Cancer Res、Mol Cancer Ther、PLoS ONE、Curr Cancer Drug Targets、JBC等雜志上發表SCI論文25篇，被引用超過600次，并參編英文專著兩部。

主要研究領域

實驗室研究方向和內容：

余四旺實驗室的研究方向為預防藥學，研究內容主要圍繞細胞對化學物質（包括藥物、致癌物、ROS等等）的應答，運用多種化學的和分子、細胞、整體動物模型等生物學手段，結合臨床樣本和數據，探索重大慢性非傳染性疾病如癌癥和糖尿病的發病機制及對其進行干預的靶點和手段。進一步的，在個體化預測疾病發展和轉歸的基礎上，利用天然的或合成的化學或生物物質，對疾病發生發展的關鍵病理環節進行個體化的針對性干預或預防性治療，以阻止、減緩或者逆轉疾病的惡化和不良預后，并促進其良性轉歸。

預防藥學的研究內容可以分為兩大部分，一是生物標志物和藥物靶標研究。生物標志物主要用于個體化預判疾病的進展/轉歸/預后以確定高危/靶人群，以及個體化預測預防藥物的藥效和毒性等并提供監測指標。這些生物標志物通常也是預防藥物干預的靶標。二是在生物標志物和藥物靶標研究的基礎上，研發安全有效的干預關鍵病理環節的預防藥物。這些藥物既可以是新研發的可食植物成分、天然藥物成分、化學合成修飾產物或者內源性生物物質，也可以是已有的經過臨床證實安全有效的預防或治療藥物。

正在進行課題：

1、氧化應激調控因子在癌癥發生發展、耐藥和放化療毒副作用中的作用及其干預手段。

2、細胞應激機制在糖尿病及其并發癥發生機制中的作用及其干預手段。

3、中藥及可食植物成分用于癌癥和糖尿病化學預防及其作用機制。

承擔基金項目：

目前承擔國家自然科學基金青年基金項目一項（重金屬細胞毒性和致癌的化學預防，21001011，課題負責人），973前期研究專項課題一項（兩種新疆特色可食植物成分用于癌癥化學預防的研究，2009CB526509），北京大學醫學部人才引進啟動基金一項（化學預防藥物基礎研究，bmu2009138-121，課題負責人），教育部博士點新教師基金一項（轉錄因子Nrf2在白血病耐藥機制中的作用，課題負責人），教育部留學人員歸國啟動基金一項。

近期發表的論文（按時間順序）：

1.Cheung KL, Yu S, Pan Z, Ma J, Wu TY, Kong AN, tBHQ-Induced HO-1 Expression Is Mediated by Calcium through Regulation of Nrf2 Binding to Enhancer and Polymerase II to Promoter Region of HO-1, Chem Res Toxicol, 2011 Epub ahead of print.

2.Que LL, Wang HX, Cao BS, Yang XD, Wang K, Yu SW*, The regulation and functions of transcription factor Nrf2 in cancer chemoprevention and chemoresistance, J Chin Pharm Sci 2011 20 (1): 5-19

3.Yu S, Khor TO, Cheung K-L, Li W, Wu T-Y, Huang Y, Foster BA, Kan YW, Kong AN, Nrf2 Expression Is Regulated by Epigenetic Mechanisms in Prostate Cancer of TRAMP Mice. PLoS One. 2010 Jan 5;5(1):e8579

4.Khor TO*, Yu S*, Barve A, Hao X, Hong JL, Lin W, Foster B, Huang MT, Newmark HL, Kong AN. Dietary Feeding of Dibenzoylmethane Inhibits Prostate Cancer in Transgenic Adenocarcinoma of the Mouse Prostate Model. Cancer Res 2009; 69(17):7096-102. * Khor T and Yu S contributed equally to this work.

5.Prawan A, Saw CL, Khor TO, Keum YS, Yu S, Hu L, Kong AN. Anti-NF-kappaB and anti-inflammatory activities of synthetic isothiocyanates: effect of chemical structures and cellular signaling. Chem Biol Interact 2009;179(2-3):202-11.

6.Yu S, Shen G, Khor TO, Kim JH, Kong AN. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Mol Cancer Ther 2008;7(9):2609-20.

7.Prawan A, Keum YS, Khor TO, Yu S, Nair S, Li W, Hu L, Kong AN. Structural influence of isothiocyanates on the antioxidant response element (ARE)-mediated heme oxygenase-1 (HO-1) expression. Pharm Res 2008;25(4):836-44.

8.Nair S, Hebbar V, Shen G, Gopalakrishnan A, Khor TO, Yu S, Xu C, Kong AN. Synergistic effects of a combination of dietary factors sulforaphane and (-) epigallocatechin-3-gallate in HT-29 AP-1 human colon carcinoma cells. Pharm Res 2008;25(2):387-99.

9.Li W, Yu S, Liu T, Kim JH, Blank V, Li H, Kong AN. Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif. Biochim Biophys Acta 2008;1783(10):1847-56.

10.Li W, Khor TO, Xu C, Shen G, Jeong WS, Yu S, Kong AN. Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. Biochem Pharmacol 2008;76(11):1485-9.

11.Khor TO, Yu S, Kong AN. Dietary cancer chemopreventive agents - targeting inflammation and Nrf2 signaling pathway. Planta Med 2008;74(13):1540-7.

12.Khor TO, Huang MT, Prawan A, Liu Y, Hao X, Yu S, Cheung WK, Chan JY, Reddy BS, Yang CS, Kong AN. Increased susceptibility of Nrf2 knockout mice to colitis-associated colorectal cancer. Cancer Prev Res (Phila Pa) 2008;1(3):187-91.

13.Cheung KL, Khor TO, Yu S, Kong AN. PEITC Induces G1 Cell Cycle Arrest on HT-29 Cells Through the Activation of p38 MAPK Signaling Pathway. AAPS J 2008;10(2):277-81

14.Barve A, Khor TO, Nair S, Lin W, Yu S, Jain MR, Chan JY, Kong AN. Pharmacogenomic Profile of Soy Isoflavone Concentrate in the Prostate of Nrf2 Deficient and Wild-Type Mice. J Pharm Sci 2008; 97(10):4528-45

15.Yu S, Kong AN. Targeting carcinogen metabolism by dietary cancer preventive compounds. Curr Cancer Drug Targets 2007;7(5):416-24.

16.Shen G, Khor TO, Hu R, Yu S, Nair S, Ho CT, Reddy BS, Huang MT, Newmark HL, Kong AN. Chemoprevention of familial adenomatous polyposis by natural dietary compounds sulforaphane and dibenzoylmethane alone and in combination in ApcMin/+ mouse. Cancer Res 2007;67(20):9937-44.

17.Kwon KH, Barve A, Yu S, Huang MT, Kong AN. Cancer chemoprevention by phytochemicals: potential molecular targets, biomarkers and animal models. Acta Pharmacol Sin 2007;28(9):1409-21.

18.Yuan X, Xu C, Pan Z, Keum YS, Kim JH, Shen G, Yu S, Oo KT, Ma J, Kong AN. Butylated hydroxyanisole regulates ARE-mediated gene expression via Nrf2 coupled with ERK and JNK signaling pathway in HepG2 cells. Mol Carcinog 2006;45(11):841-50.

19.Yu S, Hu J, Yang X, Wang K, Qian ZM. La(3+)-induced extracellular signal-regulated kinase (ERK) signaling via a metal-sensing mechanism linking proliferation and apoptosis in NIH 3T3 cells. Biochemistry 2006;45(37):11217-25.

20.Xu C, Yuan X, Pan Z, Shen G, Kim JH, Yu S, Khor TO, Li W, Ma J, Kong AN. Mechanism of action of isothiocyanates: the induction of ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2. Mol Cancer Ther 2006;5(8):1918-26.

21.Lin W, Shen G, Yuan X, Jain MR, Yu S, Zhang A, Chen JD, Kong AN. Regulation of Nrf2 transactivation domain activity by p160 RAC3/SRC3 and other nuclear co-regulators. J Biochem Mol Biol 2006;39(3):304-10.

22.Li W*, Yu SW*, Kong AN. Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5 transactivation domain. J Biol Chem 2006;281(37):27251-63. *Li, W and Yu, S equally contributed to this paper

23.Keum YS, Yu S, Chang PP, Yuan X, Kim JH, Xu C, Han J, Agarwal A, Kong AN. Mechanism of action of sulforaphane: inhibition of p38 mitogen-activated protein kinase isoforms contributing to the induction of antioxidant response element-mediated heme oxygenase-1 in human hepatoma HepG2 cells. Cancer Res 2006;66(17):8804-13.

24.Hu J, Yu S, Yang X, Wang K, Qian Z. Lanthanum induces extracellular signal-regulated kinase phosphorylation through different mechanisms in HeLa cells and NIH 3T3 cells. Biometals 2006;19(1):13-8.

25.Yu S, Yuan L, Yang X, Wang K, Ke Y, Qian ZM. La3+-promoted proliferation is interconnected with apoptosis in NIH 3T3 cells. J Cell Biochem 2005;94(3):508-19.

參編專著：

1. Kui Wang, Siwang Yu and Tianlan Zhang, Arsenic in Traditional Chinese Medicine, in Biological Chemistry of Arsenic, Antimony and Bismuth, edited by Dr. Hongzhe Sun, 2011 John Wiley & Sons, Inc., ISBN: 978-0-470-71390-7

2. Siwang Yu，Ka Lung Cheung, Wenge Li and Ah-Ng Tony Kong, Plant Phenolic Compounds - modulation of cytoprotective enzymes and Nrf2/ARE signaling, in Plant Phenolics and Human Health: Biochemistry, Nutrition, and Pharmacology, edited by Dr. Cesar G Fraga，2009 John Wiley & Sons, Inc., ISBN: 978-0-470-28721-7