Weibin Shi

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Primary Appointment

Professor, Radiology and Medical Imaging

Education

  • PhD, Pathology, McGill University

Research Disciplines

Genetics

Research Interests

Molecular and genetic determinants of atherosclerosis and cardiometabolic disorders.

Research Description

My primary research interest is in atherosclerosis, which is the cause of heart attack, stroke and peripheral arterial disease. Although mortality from atherosclerosis has had a decline in past few decades largely due to effective prevention programs, lipid lowering statin therapy and angioplasty/stenting, this disease continues to claim more lives than any other disease in the United States and other Western countries. Thus, there is a medical need to find new therapies for the disease. Inflammatory responses initiated by oxidation of LDL (bad cholesterol) trapped in the arterial wall is a key process driving the initiation, progression, and rupture of atherosclerotic plaques. However, there are no effective medicines available to intervene the inflammatory process due to lack of appropriate targets. We use powerful mouse genetics tools to search for genes and pathways acting at the level of arterial walls and have identified Rcn2 as a key regulator of cytokine production in endothelial cells. We have mapped dozens of novel genetic loci for atherosclerosis, including Ath29, Ath41, Ath42, Ath48, Ath49, Ath50, Cath1, Cath2, Cath3, Cath4, Cath5, Cath6, Cayth7, and Cath8. We are in the process of characterizing candidate genes for the loci.
Diabetic patients have up to 4-fold increased risk for having incident cardiovascular events. We have mapped multiple loci for atherosclerosis that are overlapping precisely with loci for plasma glucose. We are testing the hypothesis that there exist genetic connections between the two important diseases.
Development of effective imaging probes targeting macrophages
Macrophages are involved in the development and progression of many important chronic inflammatory diseases, including atherosclerosis, asthma, inflammatory bowel disease, and type 2 diabetes. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is currently used to diagnose inflammatory diseases involving macrophages, but accurate quantitation of macrophages has been difficult due to background uptake by other cell types. We are testing more specific macrophage imaging agents that have little or no background binding to other cell types. The formyl peptide receptors (FPRs) are abundantly expressed on the surface of macrophages. We have successfully used a FPR receptor antagonist to detect macrophages in the pancreas of mice. We are in the process of designing, synthesizing and evaluating imaging gents that can be applied to humans.

Personal Statement

I have a broad background and research experience in vascular biology, pathology, genetics, and medical imaging. I first applied the lung explant technique to the study of pulmonary artery and vein constriction and relaxation in small animals when I was a graduate at McGill. As a postdoctor, I demonstrated the first direct evidence that genetic factors in atherosclerosis act at the level of the arterial wall, developed a reliable method for isolating mouse endothelial cells, and improved bone marrow and aorta transplantation procedures for the mouse. Since I joined UVA as an independent investigator in 2001, my group has discovered dozens of novel QTLs for atherosclerosis, type 2 diabetes, dyslipidemia, neointimal hyperplasia, body weight, and circulating biomarkers and identified Soat1, Apcs, Rcn2, and Mep1a as QTL genes.

Training

  • Basic Cardiovascular Research Training Grant

Selected Publications

2023

Torikai, H., Chen, M. -H., Jin, L., He, J., Angle, J. F., & Shi, W. (2023). Atherogenesis in <i>Apoe</i><SUP>-/-</SUP> and <i>Ldlr</i><SUP>-/-</SUP> Mice with a Genetically Resistant Background. CELLS, 12(9). doi:10.3390/cells12091255

2022

Abramson, A. M., Shi, L. J., Lee, R. N., Chen, M. -H., & Shi, W. (2022). Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice. CELLS, 11(17). doi:10.3390/cells11172669

Shi, W., Li, J., Bao, K., Chen, M. -H., & Liu, Z. (2022). <i>Ldlr</i>-Deficient Mice with an Atherosclerosis-Resistant Background Develop Severe Hyperglycemia and Type 2 Diabetes on a Western-Type Diet. BIOMEDICINES, 10(6). doi:10.3390/biomedicines10061429

Shi, L. J., Tang, X., He, J., & Shi, W. (2022). Genetic Evidence for a Causal Relationship between Hyperlipidemia and Type 2 Diabetes in Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(11). doi:10.3390/ijms23116184

Li, J., Taylor, A. M., Manichaikul, A., Angle, J. F., & Shi, W. (2022). Reticulocalbin 2 as a Potential Biomarker and Therapeutic Target for Atherosclerosis. CELLS, 11(7). doi:10.3390/cells11071107

Shi, L. J., Chagari, B., An, A., Chen, M. -H., Bao, Y., & Shi, W. (2022). Genetic Connection between Hyperglycemia and Carotid Atherosclerosis in Hyperlipidemic Mice. GENES, 13(3). doi:10.3390/genes13030510

2021

Grainger, A. T., Pilar, N., Li, J., Chen, M. -H., Abramson, A. M., Becker-Pauly, C., & Shi, W. (2021). Identification of <i>Mep1a</i> as a susceptibility gene for atherosclerosis in mice. GENETICS, 219(4). doi:10.1093/genetics/iyab160

Shi, L. J., Tang, X., He, J., & Shi, W. (2021). Y Hyperlipidemia Influences the Accuracy of Glucometer-Measured Blood Glucose Concentrations in Genetically Diverse Mice. AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 362(3), 297-302.

Zhao, J., Huangfu, C., Chang, Z., Zhou, W., Grainger, A. T., Liu, Z., & Shi, W. (2021). Inflammation and enhanced atherogenesis in the carotid artery with altered blood flow in an atherosclerosis-resistant mouse strain. PHYSIOLOGICAL REPORTS, 9(11). doi:10.14814/phy2.14829

Grainger, A. T., Krishnaraj, A., Quinones, M. H., Tustison, N. J., Epstein, S., Fuller, D., . . . Shi, W. (2021). Deep Learning-based Quantification of Abdominal Subcutaneous and Visceral Fat Volume on CT Images. ACADEMIC RADIOLOGY, 28(11), 1481-1487. doi:10.1016/j.acra.2020.07.010

2020

Jones, M. B., An, A., Shi, L. J., & Shi, W. (2020). Regional Variation in Genetic Control of Atherosclerosis in Hyperlipidemic Mice.. G3 (Bethesda, Md.), 10(12), 4679-4689. doi:10.1534/g3.120.401856

Fuller, D. T., Grainger, A. T., Manichaikul, A., & Shi, W. (2020). Data on genetic linkage of oxidative stress with cardiometabolic traits in an intercross derived from hyperlipidemic mouse strains. DATA IN BRIEF, 29. doi:10.1016/j.dib.2020.105165

Fuller, D. T., Grainger, A. T., Manichaikul, A., & Shi, W. (2020). Genetic linkage of oxidative stress with cardiometabolic traits in an intercross derived from hyperlipidemic mouse strains. ATHEROSCLEROSIS, 293, 1-10. doi:10.1016/j.atherosclerosis.2019.11.034

2019

Zhao, J., Huangfu, C., Chang, Z., Grainger, A. T., Liu, Z., & Shi, W. (2019). Atherogenesis in the Carotid Artery with and without Interrupted Blood Flow of Two Hyperlipidemic Mouse Strains.. Journal of vascular research, 56(5), 241-254. doi:10.1159/000502691

Li, J., Cechova, S., Wang, L., Isakson, B. E., Le, T. H., & Shi, W. (2019). Loss of reticulocalbin 2 lowers blood pressure and restrains ANG II-induced hypertension in vivo. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 316(6), F1141-F1150. doi:10.1152/ajprenal.00567.2018

2018

Banizs, A. B., Huang, T., Nakamoto, R. K., Shi, W., & He, J. (2018). Endocytosis Pathways of Endothelial Cell Derived Exosomes. MOLECULAR PHARMACEUTICS, 15(12), 5585-5590. doi:10.1021/acs.molpharmaceut.8b00765

Grainger, A. T., Tustison, N. J., Qing, K., Roy, R., Berr, S. S., & Shi, W. (2018). Deep learning-based quantification of abdominal fat on magnetic resonance images. PLOS ONE, 13(9). doi:10.1371/journal.pone.0204071

2017

Chang, Z., Huangfu, C., Grainger, A. T., Zhang, J., Guo, Q., & Shi, W. (2017). Accelerated atherogenesis in completely ligated common carotid artery of apolipoprotein E-deficient mice. ONCOTARGET, 8(66), 110289-110299. doi:10.18632/oncotarget.22685

Garrett, N. E. I. I. I., Grainger, A. T., Li, J., Chen, M. -H., & Shi, W. (2017). Genetic analysis of a mouse cross implicates an anti-inflammatory gene in control of atherosclerosis susceptibility. MAMMALIAN GENOME, 28(3-4), 90-99. doi:10.1007/s00335-016-9677-0

Grainger, A. T., Jones, M. B., Chen, M. -H., & Shi, W. (2017). Polygenic Control of Carotid Atherosclerosis in a BALB/cJ x SM/J Intercross and a Combined Cross Involving Multiple Mouse Strains. G3-GENES GENOMES GENETICS, 7(2), 731-739. doi:10.1534/g3.116.037879

2016

Grainger, A. T., Jones, M. B., Li, J., Chen, M. -H., Manichaikul, A., & Shi, W. (2016). Data on genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice. DATA IN BRIEF, 9, 1067-1069. doi:10.1016/j.dib.2016.11.058

Grainger, A. T., Jones, M. B., Li, J., Chen, M. -H., Manichaikul, A., & Shi, W. (2016). Genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice. ATHEROSCLEROSIS, 254, 124-132. doi:10.1016/j.atherosclerosis.2016.10.011

Shi, W., Wang, Q., Choi, W., & Li, J. (2016). Mapping and Congenic Dissection of Genetic Loci Contributing to Hyperglycemia and Dyslipidemia in Mice. PLOS ONE, 11(2). doi:10.1371/journal.pone.0148462

2015

Huang, T., Banizs, A. B., Shi, W., Klibanov, A. L., & He, J. (2015). Size Exclusion HPLC Detection of Small-Size Impurities as a Complementary Means for Quality Analysis of Extracellular Vesicles.. Journal of circulating biomarkers, 4, 6. doi:10.5772/61148

Wang, Q., Grainger, A. T., Manichaikul, A., Farber, E., Onengut-Gumuscu, S., & Shi, W. (2015). Genetic linkage of hyperglycemia and dyslipidemia in an intercross between BALB/cJ and SM/J <i>Apoe</i>-deficient mouse strains. BMC GENETICS, 16. doi:10.1186/s12863-015-0292-y

Liu, S., Li, J., Chen, M. -H., Liu, Z., & Shi, W. (2015). Variation in Type 2 Diabetes-Related Phenotypes among Apolipoprotein E-Deficient Mouse Strains. PLOS ONE, 10(5). doi:10.1371/journal.pone.0120935

Zhou, W., Chen, M. -H., & Shi, W. (2015). Influence of phthalates on glucose homeostasis and atherosclerosis in hyperlipidemic mice. BMC ENDOCRINE DISORDERS, 15. doi:10.1186/s12902-015-0015-4

Zhang, Y., Kundu, B., Zhong, M., Huang, T., Li, J., Chordia, M. D., . . . Shi, W. (2015). PET imaging detection of macrophages with a formyl peptide receptor antagonist. NUCLEAR MEDICINE AND BIOLOGY, 42(4), 381-386. doi:10.1016/j.nucmedbio.2014.12.001

2014

Banizs, A. B., Huang, T., Dryden, K., Berr, S. S., Stone, J. R., Nakamoto, R. K., . . . He, J. (2014). In vitro evaluation of endothelial exosomes as carriers for small interfering ribonucleic acid delivery. INTERNATIONAL JOURNAL OF NANOMEDICINE, 9, 4223-4230. doi:10.2147/IJN.S64267

2013

Rowlan, J. S., Li, Q., Manichaikul, A., Wang, Q., Matsumoto, A. H., & Shi, W. (2013). Atherosclerosis Susceptibility Loci Identified in an Extremely Atherosclerosis-Resistant Mouse Strain. JOURNAL OF THE AMERICAN HEART ASSOCIATION, 2(4). doi:10.1161/JAHA.113.000260

Rowlan, J. S., Zhang, Z., Wang, Q., Fang, Y., & Shi, W. (2013). New quantitative trait loci for carotid atherosclerosis identified in an intercross derived from apolipoprotein E-deficient mouse strains. PHYSIOLOGICAL GENOMICS, 45(8), 332-342. doi:10.1152/physiolgenomics.00099.2012

2012

Zhang, Z., Rowlan, J. S., Wang, Q., & Shi, W. (2012). Genetic Analysis of Atherosclerosis and Glucose Homeostasis in an Intercross Between C57BL/6 and BALB/cJ Apolipoprotein E-Deficient Mice. CIRCULATION-CARDIOVASCULAR GENETICS, 5(2), 190-201. doi:10.1161/CIRCGENETICS.111.961649

Li, J., Lu, Z., Wang, Q., Su, Z., Bao, Y., & Shi, W. (2012). Characterization of <i>Bglu3</i>, a mouse fasting glucose locus, and identification of <i>Apcs</i> as an underlying candidate gene. PHYSIOLOGICAL GENOMICS, 44(6), 345-351. doi:10.1152/physiolgenomics.00087.2011

2011

Manichaikul, A., Wang, Q., Shi, Y. L., Zhang, Z., Leitinger, N., & Shi, W. (2011). Characterization of <i>Ath29</i>, a major mouse atherosclerosis susceptibility locus, and identification of <i>Rcn2</i> as a novel regulator of cytokine expression. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 301(3), H1056-H1061. doi:10.1152/ajpheart.00366.2011

Lu, Z., Yuan, Z., Miyoshi, T., Wang, Q., Su, Z., Chang, C. C., & Shi, W. (2011). Identification of <i>Soat1</i> as a Quantitative Trait Locus Gene on Mouse Chromosome 1 Contributing to Hyperlipidemia. PLOS ONE, 6(10). doi:10.1371/journal.pone.0025344

Li, J., Wang, Q., Chai, W., Chen, M. -H., Liu, Z., & Shi, W. (2011). Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility. CARDIOVASCULAR DIABETOLOGY, 10. doi:10.1186/1475-2840-10-117

2010

Jiang, B., Khandelwal, A. R., Rogers, L. K., Hebert, V. Y., Kleinedler, J. J., Zavecz, J. H., . . . Dugas, T. R. (2010). Antiretrovirals Induce Endothelial Dysfunction <i>via</i> an Oxidant-Dependent Pathway and Promote Neointimal Hyperplasia. TOXICOLOGICAL SCIENCES, 117(2), 524-536. doi:10.1093/toxsci/kfq213

Shi, W., Zhang, Z., Chen, M. -H., Angle, J. F., & Matsumoto, A. H. (2010). Genes Within the MHC Region Have a Dramatic Influence on Radiation-Enhanced Atherosclerosis in Mice. CIRCULATION-CARDIOVASCULAR GENETICS, 3(5), 409-413. doi:10.1161/CIRCGENETICS.110.957449