CV Zuobiao Yuan
Department of Surgery
University of Iowa
Hospitals and Clinics
Roy J. and Lucille A. Carver College of Medicine
University of Iowa
EDUCATION
3051 ML
500 Newton Road, Iowa City, IA 52242
Tel: 1-319-353-4935
Email: yuanzuobiao@yahoo.com
(Preferred)
Or zuobiao-yuan@uiowa.edu
2008.12-present Postdoctoral fellow, Department of Surgery, Hospitals and Clinics, Roy J. and Lucille A.
Carver College of Medicine, University of Iowa
2006.4-2008.11 Research Associate, Robert M. Berne Cardiovascular Research Center, Department of
Biochemistry and Molecular Biology & Genetics, Department of Radiology, University of Virginia
2001.9-2003.7 Postdoctoral fellow, Department of Surgery, Shanghai Institute for Digestive Surgery,
Ruijin Hospital, Shanghai Second Medical School
1996.9-2000.7 Ph.D, Medicine (Surgery), Shanghai University of Traditional Chinese Medicine, China
Thesis: Molecular study of Granule Nourishing Gan-Yin on its prevention of gallstone formation Advisor: Professor Peiting Zhu, M.D
1988.9-1993.7 M.D, Medicine, Jiangxi College of Traditional Chinese Medicine, China
HIGHLIGHTS OF CAREER
 Characterization of ligation-induced mouse acute pancreatitis model, which is the first model naturally mimics human disease and complicated with multiple organ dysfunction syndrome.
 Multiple disciplines working experience and academic background.
Medicine, genetics of complicated diseases, molecular biology, bioinformatics, system biology and physical organic chemistry.
 In 1999 to 2006, National Science Foundation of China has supported seven projects of gallstone research;
I have five of them, all as the principle investigator or the virtual principle investigator.
 Improved methodology of identifying underlying gene of quantitative trait locus. Now it will cost 2-3 years to identify a gene, instead of 15-20 years by conventional genetics methods.
 Identified the first significant quantitative trait locus of neointimal hyperplasia （ Nih1 ） .
 Found the cause-effect relationship between gallstone and atherosclerosis.
 Proposed “ Three diseases, one origin ” in gallstone, atherosclerosis and acute pancreatitis. They are all associated with cholesterol metabolism.
 Gained PhD degree of clinical medicine in four years 。
 Reviewer of multiple disciplines in National Science Foundation of China (Surgery, Pathophysiology and molecular biology).
 Reviewer of multiple international journals.
 The only Chinese surgeon in a series of international surgical and pancreas conferences.
1

CV Zuobiao Yuan
PROFESSIONAL ASSOCIATION
American Association for the Advancement of Science
American Heart Association
American Society of Gene & Cell Therapy
American Pancreatic Association
REVIEWER
America Journal of Surgery
Pancreatology
Europe Journal of Inflammation
Journal of Biological regulators & Homeostatic Agents
International Journal of Immunopathology and Pharmacology
National Science Foundation of China (Surgery, pathophysiology and molecular biology)
MEDICAL CLINIC AND RESEARCH EXPERIENCE
2008.12-present Postdoctoral fellow
Department of Surgery, Hospitals and Clinics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa
 Career highlights:
 Characterization of the model of ligation-induced pancreatitis in mice, which has multiple organ dysfunction syndromes (MODS). Completed the most cases of this model around the world .
 Adeno-associated virus (AAV) vector, the state-of-the-art gene therapy vector with high efficiency but low toxicity.
 Job focus: Gallstone pancreatitis, pathogenesis and treatment
 Surgical techniques:
Using microsurgery to ligate the bile-pancreatic duct to induce gallstone pancreatitis, and to test hypothesis through bile and pancreatic juice replacement
 Research experiences:
 Project: The National Institute of Diabetes and Digestive ad Kidney Diseases (NIDDK).
5R01DK071731. Gallstone Pancreatitis: Pathogenesis and Treatment.
 Experimental techniques: Isolated pancreatic acinar cell, AR42J cell line, Adeno-associated virus vector, a new gene therapy vector of high efficiency and low toxicity.
 Attended conferences
2010. American Pancreas Association annual meeting, Chicago, USA
2010. Veterans Administration Surgeon annual meeting, Indianapolis, USA
2

CV Zuobiao Yuan
2009. American Pancreas Association annual meeting, Honolulu, USA
2009. Pancreas Club annual meeting, Chicago, USA
2009. Veterans Administration Surgeon annual meeting, Boston, USA
2006.4-2008.11 Research Associate
Robert M. Berne Cardiovascular Research Center and Department of Radiology, University of Virginia
 Career highlights:
 Found the first significant quantitative trait locus of neointimal formationNih1 .
 Improved methodology of identifying genes underlying quantitative trait locus.
Identified an atherosclerosis gene in 2.5 years , which usually costs 15-20 years .
 Job focus: Genetics of complex diseases such as atherosclerosis and neointimal formation.
 Surgery techniques: Animal surgery (Microsurgery such as transplantation of mouse aorta and mouse carotid injury)
 Research experience:
 Research project: The National Heart, Lung and Blood Institute (NHLB), 5R01HL082881. Genetics analysis of neointimal hyperplasia.
 Bioinformatics: Quantitative trait locus, R/qtl, Matlab (Pseudomarker programs), Ingenuity pathway analysis, Haplotype
 Experimental techniques: Van Gieson staining, Inbred mice, Cogenic mice, Transgenic, Knock-out, primary culture of vascular endothelium and smooth muscle cells, RNAi, Microarray, Immunobloting,
ELISA,
 Attended conferences:
2008. Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference. Atlanta, Georgia
2007. Experimental Biology 2007, Washington DC
2003.9 -2006 .4 Associate professor
Applied Genomics laboratory, Health Science Center, Shanghai Institutes for Biology Science, Chinese
Academy of Science
 Career highlights:
 Elucidated the cause and effect relationship between gallstone and atherosclerosis
 Introduced physical organic chemistry into research area of lipid metabolism
 Job focus: Technical platform of microarray and associated bioinformatics, lipid metabolism diseases
3

CV Zuobiao Yuan
 Research experiences:
 Grants:
1.
National Science Foundation of China. 30500201. The difference of cholesterol metabolism in inbred mice during the formation of gallstone and atherosclerosis.
2.
Shanghai Committee of Education. T0304. System biology and gallstone: Pathogenesis and treatment.
 Relevant grant:
1.
Key basic research project of Shanghai Committee of Science. 04JC14084. To predict drug addiction through bioinformatics and SNP technology
2.
Key project of Shanghai Municipality. 044319209. Gene expression profile analysis and drug target identification of human atherosclerosis tissue.
3.
National Science Foundation of China. 30672042. The role of nuclear factor LXR and FXR in liver lipid metabolism and gallstone formation.
4.
Chinese Academy of Science. Application of system biology in malignant tumor genesis and targeted therapy.
 Bioinformatics: Matlab (Self organization map), TM4, GenMAPP pathway analysis
 Experimental techniques: Hydrophobic lipophilic interaction, HPLC, Microarray, Real time PCR,
Immunobloting, lipid analysis, inbred mice
 Attended conference: 2004 Falk Symposium No. 139. Gallstones: Pathogenesis and Treatment.
Freiburg, Germany
2001.9-2003 .7 Postdoctoral Fellow
Institutes of Digestive Surgery, Ruijin Hospital, Shanghai Second Medical University
 Career highlights
 As the second postdoctoral fellow of this department
 Focused on both clinic and research. As a key member, helped the research team gained grant from
National Science Foundation of China again after several years.
 Introduced bioinformatics into research of gallstone pathogenesis.
 Job focus: Clinic and research of surgical pancreatic and biliary diseases.
 Surgical techniques: Managed wards independently. Major diseases included acute abdomen such as acute pancreatitis, gallstone and digestive tumor. Involved in ERCP, and rotated ICU. Major operations included debridement of acute necrotizing pancreatitis, cholesystectomy, pancreatic cancer Child resection, and resection of gastric and colon tumor.
 Research experiences:
4

CV Zuobiao Yuan
 Grant: National Science Foundation of China. 3-271272. Identification of gallstone susceptible locus using whole genome scanning. Key member.
 Experimental techniques: Microarray and associated bioinformatics, real time PCR.
2000.8-2001.9 Attending Surgeon
Department of Surgery, Shanghai No.2 Hospital
 Job focus: Surgical techniques: General surgery. Responsible for training surgical resident and intern.
Major operation included minimal invasive surgery, and general surgery, such as appendix, inguinal hernia, cholecystitis, gallstone, digestive tumors
1996.9-2000.7 Ph.D candidate, attending surgeon
Department of Surgery, Shanghai University of Traditional Chinese Medicine
 Career highlight:
 Obtain Ph.D degree in four years (Usually six years).
 Clinical surgical doctor degree.
Gained support from National Science Foundation of China, and completed a NSFC project simultaneously.
 Using technology of molecular biology to investigate prevention mechanism of traditional Chinese medicine.
 Job focus: General surgery and research of surgical biliary diseases.
 Surgical techniques: Operations of biliary surgery such as cholecystectomy, bile duct exploration, biliary tract plastic and choledochoscope. Surgery of digestive tumor and acute abdomen.
 Research experience:
 Grants:
 Natural Science Foundation of China. 39970916 “Regulation of liver cholesterol 7αhydroxylase and bilirubin uridine diphosphate glucuronosyltransferase(B-UGT) mRNA with liver-coursing and gallbladder-purging therapy method.” Virtual PI.
 Natural Science Foundation of China. 39870933 “Further study of prevention and treatment in pigment gallstone with Granule Nourishing Gan-Yin”
 Associated research experience:
1.
Program of “100 talented people in 21 st century”, Shanghai municipality. “Study of regulation on systemic inflammatory response syndrome of acute biliary infection with heat-clearing by purgation therapy method”
2.
State new medicine foundation of China project. “ Pre-clinical trial of phase Ⅱ of Granule
Nourishing Gan-Yin”
3.
Science and technology development foundation of Shanghai. “Development study of new medicine: Capsule Qingdan”
5

CV Zuobiao Yuan
4.
Cooperation project of Shanghai commission of science and technology. “Study of regulation on cytokine and intestinal mucosa barrier in acute biliary infection treated with Tablet
Jinghong”
5.
Cooperation project of Shanghai commission of science and technology. “Study of tertiary prevention on gallstone: Research of new Chinese herb medicine: Capsule Danshijing”
1993.9-1996.7 Resident
Internal Medicine, hospital of Suichuan county, China
 Job focus: Pediatrics and internal medicine. Major diseases included pediatric acute pneumonia compli cated by acute cardiac dysfunction, digestive ulcer, chronic colonitis.
HONORS AND AWARDS
2010
2010
2005
2004
2004
2003
2003
2001
1999
Young Investigator Award, American Pancreatic Association, Chicago, IL
Award of resident research, Department of Surgery, University of Iowa
General project award. Natural Science Foundation of China. 30500201
Key project of basic scientific research. Shanghai Commission of Science and Technology, China,
04JC14084
Major project for novel drug development. Shanghai Commission of Science and Technology, China,
044319209
Science and technological achievement award, Shanghai commission of science and technology,
China. 9312003Y0180
Science and technological achievement award, Shanghai Commission of Science and Technology,
China. 9312003Y0179,
Diplomate of Physicians, Health Bureau of Shanghai, China
Scholarship for doctoral study, Third Class Award, Shanghai University of Traditional
Chinese Medicine, China
1999
1998
1998
1995
1994
1992
General project. Natural Science Foundation of China. 39970916
Scholarship for graduate study, Third Class Award, Shanghai University of Traditional Chinese
Medicine, China
General project. Natural Science Foundation of China. 39870933
Award for “Model physician”, Suichuan Hospital, China
Diplomate of Physicians, Health Bureau of Jiangxi Province, China
Scholarship for undergraduate study, First Class Award, Jiangxi College of Traditional Chinese
1991
Medicine
Scholarship for undergraduate study, Second Class Award, Jiangxi College of Traditional Chinese
Medicine
1990 Scholarship for undergraduate study, Third Class Award, Jiangxi College of Traditional Chinese
Medicine
PUBLICATIONS
BOOK
Yuan ZB, Zhu DS, Yan ZY. Gallstone and cholelithiasis. Shanghai Far East Press. Shanghai, 2000
PAPERS
6

CV Zuobiao Yuan
1.
Yuan Z, Meyerholz DK, Twait EC, Kempuraj D, Williard DE, Samuel I. Systemic Inflammation with
Multiorgan Dysfunction Is the Cause of Death in Murine Ligation-Induced Acute Pancreatitis. J Gastrointest
Surg. 2011 Jul 29. [Epub ahead of print]. IF 2.7
2.
Williard D, Twait E, Yuan Z, Carter AB, Samuel I. NF-kB-dependent gene transcription in CCK- and
TNF-α-stimulated isolated acinar cells is regulated by p38 MAP kinase. American Journal of Surgery
2010;200(2):283-90. IF 2.4
3.
Samuel I, Yuan Z, Williard D, Twait E, Kempuraj D. A novel model of severe gallstone pancreatitis: Murine pancreatic duct ligation results in systemic inflammation and substantial mortality (Rapid Communication).
Pancreatology 2010;10(5):536-544. IF 3.0
4.
Yuan Z, Pei H, Roberts DJ, Zhang Z, Rowlan JS, Matsumoto AH, Shi W. Quantitative trait locus analysis of neointimal formation in an intercross between C57BL/6 and C3H/HeJ apolipoprotein E-deficient mice. Circ
Cardiovasc Genet. 2009 ,2:220. IF 14.6
5.
Yuan Z, Miyoshi T, Bao Y, Sheehan JP, Matsumoto AH, Shi W. Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility. Am J
Physiol Heart Circ Physiol. 2009,296:H1336. IF 3.6
6.
Yuan Z, Su Z, Miyoshi T, Rowlan JS, Shi W. Quantitative trait locus analysis of circulating adhesion molecules in hyperlipidemic apolipoprotein E-deficient mice. Mol Genet Genomics. 2008,280:375. IF 2.8
7.
Yuan Z, Petersen EJ, Miyoshi T, Hirohata S, Li JZ, Shi W, Angle JF. SiRNA silencing reveals role of vascular cell adhesion molecule-1 in vascular smooth muscle cell migration. Atherosclerosis. 2008,198:301. (Co-First
Author) IF 4.6
8.
Yuan Z, Miyoshi T, Shi W. Association of a Vcam1 mutation with atherosclerosis susceptibility in diet-induced models of atherosclerosis. Atherosclerosis. 2008,196:234. (Co-First Author) IF 4.6
9.
Zhu M, Ji G, Jin G, Yuan Z. Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis. Nutr Metab (Lond). 2009,;6:43. IF 3.0
10.
Yuan ZB, Han TQ, Jiang ZY, FeiJ, Zhang Y, Qin J, TianZJ, Shang J, Jiang ZH, Cai XX, Jiang Y, Zhang SD.
Expression profiling suggests a regulatory role of gallbladder in lipid homeostasis. World Journal of
Gastroenterology, 2005, 14 ： 2109 IF 2.1
11.
Yuan ZB, Han TQ, Jiang ZY, Fei J, Qin J, Tian ZJ, Jiang ZH, Cai XX, Shang J, Jiang Y, Zhang SD.
Investigation of gene expression profile in normal gallbladder tissue. Journal of Surgery Concepts &
Practice. 2003,8:103-106.
12.
Yuan ZB, Jiao YZ, Zhang XL, Gao J, Song HR, Zhang JZ, Zhu PT. Regulation of Granule Nourishing
Gan-Yin on the expression of cholecystokinin receptor mRNA in guinea pig. Chinese Journal of experimental Surgery. 2003, 20: 23-24.
13.
Yuan ZB, Zhu PT, Zhang XL, Jiang YZ, Zhang JZ, Zhang HY, Gao J, Shen P. Hypercholesterolemia and the formation of gallbladder pigment stone in guinea pig. Chinese Journal of Surgery. 2003,41:946.
14.
Yuan ZB. Insight on prevention and treatment of gallstone. New Journal of Traditional Chinese Medicine.
1999, 31(11): 54
ORAL PRESENTATION AND INVITED LECTURE
Adeno-associated virus-mediated in vivo expression of dominant negative ERK improves mortality in a novel murine model of gallstone pancreatitis, Chicago, November, 2010
7

CV Zuobiao Yuan
Pancreatic duct ligation-induced acute pancreatitis in rats is associated with acute lung injury. 2010 VA surgeon annual meeting, Indianapolis, May, 2010
Microarray analysis of gene expression in the mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility.
Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference
2008. Atlanta, Georgia, April, 2008
Tumor related genes up-regulated in gallstone affected gallbladder---analysis by cDNA array hybridization.
International workshop on biliary tract cancer (Co-sponsored by NIH) Shanghai, China July, 2004
Abstracts published
1. Williard DE, Twait E, Yuan Z, Samuel I. RGS-6 negatively regulates TNF-alpha-stimulated activation of
NF-kB in acinar cells. Pancreas 2009;38(8):1057.
2. Twait E, Williard D, Yuan Z, Samuel I. Carbachol-stimulated activation of ERK and p38 MAPK modulates
NFkB activity in AR42J cells. Pancreas 2009;38(8):1057.
3. Kempuraj D, Yuan Z, Samuel I. Glia maturation factor is expressed in the mouse pancreas and lung. Pancreas
2010;38(8):1327.
4. Samuel I, Yuan Z, Meyerholz D, Twait E, Williard D, Kempuraj D. Murine pancreatic duct ligation causes acute lung injury and 100% mortality: a novel model for investigating acute pancreatitis. Pancreas
2010;39(8):1344.
5. Yuan Z, Williard D, Twait E, Kempuraj D, Samuel I. Adeno-associated virus-mediated in vivo expression of dominant negative ERK improves mortality in a novel murine model of gallstone pancreatitis. Pancreas
2010;39(8):1359.
Abstracts presented:
1. Williard DE, Twait E, Tephly L, Carter AB, Yuan Z, Samuel I. NF-kB-dependent gene transcription in CCK- and TNF-stimulated isolated acinar cells is mediated by p38 MAP kinase. Annual Meeting of the Association of VA Surgeons. Boston, MA, April 2009.
2. Williard DE, Twait E, Yuan Z, Samuel I. RGS-6 negatively regulates TNF-alpha-stimulated activation of
NF-kB in acinar cells. Annual Meeting of the American Pancreatic Association; Honolulu, HI, November
2009.
3. Twait E, Williard D, Yuan Z, Samuel I. Carbachol-stimulated activation of ERK and p38 MAPK modulates
NFkB activity in AR42J cells. Annual Meeting of the American Pancreatic Association; Honolulu, HI,
November 2009.
4. Yuan Z, Meyerholz D, Kempuraj D, Williard D, Twait E, Kirch J, Samuel I. Pancreatic duct ligation-induced acute pancreatitis in rats is associated with acute lung injury. Annual Meeting of the Association of VA
Surgeons. Indianapolis, IN, May 2010.
5. Yuan Z, Williard D, Twait E, Kempuraj D, Samuel I. Adeno-associated virus-mediated expression of dominant negative ERK improves mortality in a novel murine model of gallstone pancreatitis. Annual
Meeting of the American Pancreatic Association; Chicago, IL, November 2010.
8

CV Zuobiao Yuan
6. Kempuraj D, Yuan Z, Samuel I. Glia maturation factor is expressed in the mouse pancreas and lung. Annual
Meeting of the American Pancreatic Association; Chicago, IL, November 2010.
7. Samuel I, Yuan Z, Meyerholz D, Twait E, Williard D, Kempuraj D. Murine pancreatic duct ligation causes acute lung injury and 100% mortality: a novel model for investigating acute pancreatitis. Annual Meeting of the American Pancreatic Association; Chicago, IL, November 2010.
8. Yuan Z, Miyoshi T, Bao Y, Sheehan JP, Matsumoto AH, Shi W. Microarray analysis of gene expression in the mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility.
Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference; Atlanta, GA, April 2008
CERTIFICATES
American Medical Association/Physician Recognition Award
American College of Surgeons
Association of VA surgeons
The Pancreas Club
International Standard Organization
University of Virginia (Aseptic animal surgery)
Microsoft Co.Ltd (Visual C++ 6.0 )
Microsoft Co.Ltd (Visual Basic 6.0 )
Physician license, Bureau of Health, Shanghai municipality, China
Physician license, Bureau of Health, Jiangxi Province, China
ONGOING PROJECT
Source: National Institute of Diabetes and Digestive and Kidney Diseases
Title: Gllstone Pancreatitis: Pathogenesis and Treatment
Abstract: Gallstone pancreatitis is common and is potentially fatal. Enteral exclusion of bile-pancreatic juice by the stone causes feedback hyperstimulation of the exocrine pancreas that induces pancreatic overproduction of acute inflammatory mediators. Systemic spread of acute pancreatic inflammation leads to multi-organ failure which is the major cause of death from acute pancreatitis. However, no specific treatment is currently available as the pathogenic mechanisms are not well understood. We have used the rodent model of duct ligation-induced acute pancreatitis as an experimental analogy to investigate disease pathogenesis. We acknowledge the fact that species-related variations between rodents and humans may limit the clinical relevance and potential applications of these findings. However, useful information can still be garnered from these studies. Using a unique and original surgical model, the Donor Rat Model, we showed that enteral bile-pancreatic juice replacement substantially ameliorates pancreatic morphological changes in the early stages of ligation-induced acute pancreatitis and inhibits pancreatic overproduction of acute inflammatory mediators. We concluded that bile-pancreatic juice exclusion from gut plays an important role in exacerbating acute pancreatitis in our experimental model. Using our donor model, we have shown that stress kinase activation in pancreata of rats and mice after duct ligation is ameliorated by duodenal bile-pancreatic juice replacement. We present new evidence that p38 and ERK regulate NFkB-mediated gene transcription in an exocrine pancreatic (AR42J) cell line.
Furthermore, we show that 24 h of duct ligation in the mouse is associated with pulmonary ERK activation and acute lung injury. We hypothesize that the local and systemic acute inflammatory response in gallstone
9

CV Zuobiao Yuan pancreatitis is worsened by the enteral exclusion of bile-pancreatic juice that causes feedback hyperstimulation of the exocrine pancreas to activate pro-inflammatory pathways in the presence of an obstructed duct. Aim 1: To determine the mechanism of activation of pro-inflammatory pathways in isolated pancreatic acinar cells. Aim 2:
To determine the mechanism of pancreatic production of cytokines, chemokines, and reactive oxygen species in the early stage of ligation-induced acute pancreatitis. Aim 3: To determine the mechanism of development of the local and systemic inflammatory response in the late stage of ligation-induced acute pancreatitis. We use novel approaches, such as in vivo gene modulation, to investigate mechanisms of disease pathogenesis by inhibition of
ERK and p38. A role for enteral bile-pancreatic juice exclusion in the pathogenesis of gallstone pancreatitis, and the systemic inflammatory response syndrome, may provide the rationale for much needed therapeutic initiatives for a condition that is associated with considerable morbidity and mortality - and for which no specific therapy is known. PUBLIC HEALTH RELEVANCE. Acute pancreatitis is a common inflammatory condition of the pancreas that is potentially fatal. The commonest cause of acute pancreatitis world-wide is gallstones. This research proposal investigates how gallstone obstruction of the pancreatic duct may initiate acute inflammation of the pancreas. A better understanding of these processes will help to improve the treatment of this potentially fatal condition.
Keywords: Pancreatitis, Gallstone, Stress Activated Proteinase Kinase, Pancreatic and bile juice replacement, Gene therapy, Adeno-associated Virus
Finished Projects
PROJECT 1 Source: National Science Foundation of China
Title: Difference of cholesterol metabolism in inbred mice during its formation of gallstone and atherosclerosis.
Abstract: The major goals of this project are to determine the dynamic relationship of atherosclerosis and gallstone. In inbred mice namely C57BL/6, which is susceptible to both gallstone and atherosclerosis, will be observed to discover if the cholesterol metabolism is different in those two diseases, and C3H/He, resistant to both disease, will be used as control. Meanwhile, mice liver will be hybridized to microarray to find the pivot targets, and the Hydrophobic Lipophlic Interaction of lipids in both serum and bile will be measured; finally, the detail function of targets and their role in lipid metabolism will be further discussed.
Key words: bile, gallstone, artery, atherosclerosis, liver, genetic susceptibility, cholesterol esters, hydrophobic lipophilic interaction, inbred mice, light microscopy, microarray, self-organize map, bioinformatics, RNA interference, real-time polymerase chain reaction
PROJECT 2 Source: Shanghai Commission of Science and Technology
Title: Investigate mechanism of Chinese herbs on its prevention of gallstone and hypercholesterolemia through system biology methods
Abstract: We have developed two
Traditional Chinese Medicine Patent Prescription s for the prevention of gallstone and hyperlipidemia. Due to their complicate ingredients and multiple level targets, it is very difficult to find the effective compounds and the real targets. In this project, we will use methods of fingerprint profile to fix the ingredients those products. Then, microarray and 2D gel will be used in the inbred mouse model. Multiple bioinformatics approaches will be used to construct network of chemical molecules, mRNA and protein.
Keywords:
System biology, fingerprint profile, microarray, 2D gel, Bioinformatics, gallstone, Traditional Chinese Medicine
Associated Project
Source: National Heart, Lung and Blood Institute
Title: Genetic analysis of neointimal hyperplasia
10

CV Zuobiao Yuan
Summary: We hypothesize that genetic factors that influence the induction of cytokines and growth factors or that modulate the proliferation of vascular smooth muscle cells contribute to the variation in neointimal hyperplasia of the two strains. To test this hypothesis, B6.apoE-/- mice will be mated with CSH.apoE-/- mice to generate F1 mice, which will be subsequently intercrossed to generate a cohort of F2 mice. The male F2 mice, together with male F1 and two parental strains, will be subject to endothelial denudation of the left common carotid artery. Neointimal thickening will be quantitated by light microscopy. Blood will be collected for assessment of fasting lipid and inflammatory marker levels. Genome-wide scans will be performed using microsatellite markers to define the genetic loci that are linked to differences in the phenotypes between B6 and
C3H strains. After the genome screen has detected chromosomal regions that show linkage with neointimal lesions, we will type additional closely spaced polymorphic markers to narrow the regions. One to two major
QTLs for neointimal hyperplasia will be dissected through construction and analysis of congenic strains.
Thesaurus Terms: apolipoprotein E, genetic regulation, hyperplasia, restenosis, vascular endothelium, blood vessel prosthesis, cardiovascular injury, genetic strain, genetic susceptibility, hyperlipidemia, inflammation, intraluminal angioplasty, medical complication, quantitative trait loci, laboratory mouse, linkage mapping
Associated research experience:
2007
2006
2004
5R01HL075433-04, QTL analysis of carotid atherosclerosis, NIH
5R01HL071844-04, Regulation of atherosclerosis susceptibility, NIH
Key project of basic scientific research. Shanghai commission of science and technology, China,
04JC14084. “To study the molecular mechanism of drug addict mainly through bioinformatics
2004 and SNPs”
Major project for novel drug development. Shanghai commission of science and technology,
2003
China, 044319209. “ Gene expression profile and drug targets validation in large population sample of human atherosclerosis”
General project. Natural Science Foundation of China. 30271272 “ To identify gallstone susceptible genes mainly through Genome Scan and fine mapping”
1999 General project. Natural Science Foundation of China. 39970916 “Regulation of liver cholesterol
7αhydroxylase and bilirubin uridine diphosphate glucuronosyltransferase(B-UGT) mRNA with
1999 liver-coursing and gallbladder-purging therapy method.”
Program of “100 talented people in 21 st century”, Shanghai municipality. “Study of regulation on systemic inflammatory response syndrome of acute biliary infection with heat-clearing by purgation therapy method”
1999 State new medicine foundation of China project. “ Pre-clinical trial of phase Ⅱ of Granule
1998
1998
1997
1997
Nourishing Gan-Yin”
General project. Natural Science Foundation of China. 39870933 “Further study of prevention and treatment in pigment gallstone with Granule Nourishing Gan-Yin”
Science and technology development foundation of Shanghai. “Development study of new medicine: Capsule Qingdan”
Cooperation project of Shanghai commission of science and technology. “Study of regulation on cytokine and intestinal mucosa barrier in acute biliary infection treated with Tablet Jinghong”
Cooperation project of Shanghai commission of science and technology. “Study of tertiary prevention on gallstone: Research of new Chinese herb medicine: Capsule Danshijing”
References
11

CV Zuobiao Yuan
Isaac Samuel, M.D, Associate professor, Department of Surgery, UI Obesity Surgery Program ,Division of
Gastrointestinal, Minimally Invasive and Bariatric Surgery, Hospitals & Clinics, Roy J. and Carver College of
Medicine, University of Iowa
Tel: 1-319-384-7359 Email: isaac-samuel@uiowa.edu
Weibin Shi, M.D, Ph,D, Associate professor, Robert M. Berne Cardiovascular Research Center, Department of
Biochemistry and Molecular Biology & Genetics, Department of Radiology, University of Virginia
Tel: 1-434-243-9420 Email: ws4v@virginia.edu
Shengdao Zhang, M.D. Emeritus professor of medicine, Department of surgery, Shanghai Institutes for
Biological Science, Ruijin Hospital, College of Medicine, Shanghai Jiao Tong University, Shanghai, China,
200025
Tel: 0086-21-64370045-611002
Email: digsurgrj@yahoo.com.cn
Pei-Ting Zhu, M.D., Professor of Medicine, Distinguished physician of traditional Chinese medicine in
Shanghai, Department of biliary surgery, Longhua Hospital, Shanghai University of Traditional Chinese
Medicine, Shanghai, China, 200032
Tel: 86-21-64385700-2314
E mail: shanghaizxl@sina.com
12