北京大学

余四旺：理学博士，副教授，硕士生导师

电话：（010）82801539

Email：swang_yu@bjmu.edu.cn

实验室主页：http://www.chemoprevention.net

通讯地址：北京市海淀区学院路38号药学院308室 邮编：100191

1996年获四川轻化工学院工学学士学位，2000年获华中科技大学理学硕士学位；2003年获北京大学药学院理学博士学位,博士期间主要研究稀土元素生物效应的分子与细胞机理；2004年12月至2008年12月在美国新泽西州立大学从事博士后研究，主要研究天然植物成分用于肿瘤化学预防的动物模型与分子和细胞机理；2008年12月至今任北京大学药学院副教授，主要从事预防药学研究。近年来在Cancer Res、Mol Cancer Ther、PLoS ONE、Curr Cancer Drug Targets、JBC等杂志上发表SCI论文25篇，被引用超过600次，并参编英文专著两部。

主要研究领域

实验室研究方向和内容：

余四旺实验室的研究方向为预防药学，研究内容主要围绕细胞对化学物质（包括药物、致癌物、ROS等等）的应答，运用多种化学的和分子、细胞、整体动物模型等生物学手段，结合临床样本和数据，探索重大慢性非传染性疾病如癌症和糖尿病的发病机制及对其进行干预的靶点和手段。进一步的，在个体化预测疾病发展和转归的基础上，利用天然的或合成的化学或生物物质，对疾病发生发展的关键病理环节进行个体化的针对性干预或预防性治疗，以阻止、减缓或者逆转疾病的恶化和不良预后，并促进其良性转归。

预防药学的研究内容可以分为两大部分，一是生物标志物和药物靶标研究。生物标志物主要用于个体化预判疾病的进展/转归/预后以确定高危/靶人群，以及个体化预测预防药物的药效和毒性等并提供监测指标。这些生物标志物通常也是预防药物干预的靶标。二是在生物标志物和药物靶标研究的基础上，研发安全有效的干预关键病理环节的预防药物。这些药物既可以是新研发的可食植物成分、天然药物成分、化学合成修饰产物或者内源性生物物质，也可以是已有的经过临床证实安全有效的预防或治疗药物。

正在进行课题：

1、氧化应激调控因子在癌症发生发展、耐药和放化疗毒副作用中的作用及其干预手段。

2、细胞应激机制在糖尿病及其并发症发生机制中的作用及其干预手段。

3、中药及可食植物成分用于癌症和糖尿病化学预防及其作用机制。

承担基金项目：

目前承担国家自然科学基金青年基金项目一项（重金属细胞毒性和致癌的化学预防，21001011，课题负责人），973前期研究专项课题一项（两种新疆特色可食植物成分用于癌症化学预防的研究，2009CB526509），北京大学医学部人才引进启动基金一项（化学预防药物基础研究，bmu2009138-121，课题负责人），教育部博士点新教师基金一项（转录因子Nrf2在白血病耐药机制中的作用，课题负责人），教育部留学人员归国启动基金一项。

近期发表的论文（按时间顺序）：

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.

参编专著：

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