Endocrinology, Metabolism and Clinical Nutrition

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Yi (Sherry) Zhang, PhDYi (Sherry) Zhang, PhD

Assistant Professor
Department of Medicine
Human & Molecular Genetics Center
Medical College of Wisconsin

PhD, Molecular Biology (Marquette University, Milwaukee, USA)
Post-doctoral Fellowship in Genetics of Human Dyslipidemia (Medical College of Wisconsin, Milwaukee, USA)

Previous Positions:
Research Scientist, Genetics and Epigenetics of the Metabolic Syndrome (MCW, Milwaukee, USA)

TOPS Obesity and Metabolic Research Center
Medical College of Wisconsin
8701 Watertown Plank Road, Milwaukee, WI, 53226
Phone: (414) 955-4013
Fax: (414) 955-6386
Email: yzhang@mcw.edu

Investigative Interests:
Metabolic Syndrome (MetS), Obesity, Epigenetics of adult and adolescent MetS

Ongoing Research: 
Metabolic syndrome (MetS) affects one of every three Americans and dramatically increases their risk for cardiovascular disease. Individual phenotypic components of MetS such as skewed body fat distribution and insulin resistance are consequences of the dynamic interaction between nature (the genome) and nurture (the environment). Genomic CpG methylation status, an epigenetic regulator of gene expression, is one of the prominent mechanistic links between the genome and the environment. Studying the quantitative relationship of MetS traits and genomic methylation status is therefore likely to unravel genetic elements and pathways that have not been identified by previous genomic studies focusing on primary sequence variants. We, the TOPS Obesity and Metabolic Research Center, possess a unique study population that consists of multi-generational extended families of European origin that have been phenotyped for 42 clinical and biological components of the MetS. Our large pedigrees also contain children undergoing puberty, a crucial stage in the development of MetS in adults. I am interested in applying state-of-the-art high throughput genomic technologies to the investigation of pathogenesis of MetS using our unique population. I recently proposed to study the relationship between regional and global DNA methylation and these 42 MetS phenotypes in our families. We are using genome-wide SNP genotype data as well as genome-wide gene expression data of our most informative pedigrees to help the prioritization of our candidate genes for detailed CpG methylation study.

      We have also established two distinct systems in which a genome-wide agnostic research for MetS-associated CpG methylation can be performed. One of these two systems is next-generation sequencing based, namely MBD-isolated genomic sequencing (MiGS), and the other one is the microarray-based platform Infinium Meth450, commercially offered by Illumina. Recently, with my close collaborator, pediatric endocrinologist Dr. Omar Ali (MCW), I have been funded to conduct a pilot study on applying these two genome-wide technologies to studying “gene-environment interaction mediated by epigenetic changes during puberty”. We aimed to report findings on the heritability of CpG methylation as well as age- and sex effects on this epigenetic feature; and to correlate it with phenotypic components of the MetS. The preliminary data generated from this effort will lay the ground work for us to conduct a formal study on a larger scale, where our power of detecting biologically relevant signals will be enhanced. To make sure the epigenetic elements that we find are functional, we apply a validation procedure to the testing of our candidates. We will validate the functionality of the statistically associated genomic methylation using the luciferase reporter assay. These associations will be also replicated in a second family cohort of distinct ethnical background.

Selected Peer Review Publications (*= co-first author):

  1.  Baye T.M.*, Zhang Y.* Smith E., Hillard C.J., Gunnell J., Myklebust J., James R., Kissebah A.H., Olivier M. * and Wilke R.A. * (2008) Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index. Pharmacogenomics 9 (11): 1647-1656
  1. Zhang Y.*, Sonnenberg G.E.*, Baye T.M.*, Littrell J., Gunnell J., DeLaForest A., MacKinney E., Hillard C.J., Kissebah A.H., Olivier M. and Wilke R.A. (2010) Obesity-related dyslipidemia associated with FAAH, independent of insulin response, in multigenerational families of Northern European descent. Pharmacogenomics 10 (12): 1929-1939
  1. Smith E.M.*, Zhang Y.*, Baye T.M., Gawrieh S., Cole R., Blangero J., Carless M.A., Curran J.E., Dyer T.D., Abraham L.J., Moses E.K., Kissebah A.H., Martin L.J., and Olivier M. (2010) INSIG1 influences obesity-related hypertriglyceridemia in humans. Journal of Lipid Research 51: 701-708
  1. Zhang Y.*, Smith E.M. *, Baye T.M., Kissebah A.H., Martin L.J., and Olivier M. (2010) Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels. Physiological Genomics 42: 168-176
  1. Wu C., Chen S., Shortreed M.R., Kreitinger G. M., Yuan Y., Frey B. L., Zhang Y., Mirza S., Cirillo L. A., Olivier M., and Smith L. M.. Sequence-specific capture of protein-DNA complexes for mass spectrometric protein identification. (2011) PLoS One 6: e26217
  2. Zhang Y. **, Kent Jr. J.W., Olivier M., Ali O., Broeckel U., Abdou R.M., Dyer T.D. Comuzzie A., Curran J.E., Carless M.A., Rainwater D.L., Göring H.H.H., Blangero J. and Kissebah A.H. (2013) QTL-based association analyses reveal novel genes influencing pleiotropy of Metabolic Syndrome (MetS). (2013) Obesity DOI: 10.1002/oby.20324

  3. Zhang Y. **, Kent Jr. J.W., Lee A., Cerjak D., Ali O., Diasio R. Olivier M., Blangero J., Carless M.A., and Kissebah A.H. (2013) Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a Northern European family population. BMC Medical Genomics 2013 6:9 doi:10.1186/1755-8794-6-9

  4. Zhang Y. **, Kent Jr. J.W., Olivier M., Ali O., Abdou R.M., Dyer T.D., Curran J.E., Carless M.A., Göring H.H.H., Blangero J. and Kissebah A.H. A comprehensive analysis of adiponectin QTLs using SNP association, SNP cis-effects on peripheral blood gene expressions and gene expression correlation identified novel metabolic syndrome (MetS) genes with potential role in carcinogenesis and systemic inflammation. BMC Medical Genomics.2013, 6:14. DOI: 10.1186/1755-8794-6-14

Book Chapters:

Zhang Y. *, Smith E. *, and Olivier M. (2008).  Putting the Invader® Assay to Work: Lab Application and Data Management. In: Single Nucleotide Polymorphisms: Methods and Protocols (the Methods in Molecular Biology series), 2nd edition. Vol: 578: page 363-377. Humana Press, Totowa, NJ


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