Olivier, Michael Ph.D.
Assistant Professor
Specialization: Human disease genetics, human sequence variation,
expression analysis, proteomics, technology development
Tel: (414) 456-4968 Dr. Olivier's CV
Email:
Our
laboratory is trying to understand how genetic sequence variation
affects gene function and ultimately human disease. We utilize
genomics tools to discover single nucleotide polymorphisms (SNPs)
by sequencing, genotype these SNPs in large numbers of individuals
to understand patterns of linkage disequilibrium and haplotypes
across extended regions of the human genome, analyze potential
association of SNPs and haplotypes with complex human disorders,
and explore the effect of haplotypes on gene expression and protein
levels.
Our projects focus on the metabolic syndrome, a disorder encompassing
obesity, hyperlipidemia, insulin resistance, and hypertension.
This common human syndrome often also leads to cardiovascular complications.
As part of the Metabolic Risk Complications of Obesity Genes (MRC-OB)
study at MCW, we are investigating genomic regions identified by
linkage analysis in an attempt to use linkage disequilibrium and
haplotype structure analysis to identify the causal gene(s) for
alterations in the lipid profile such as elevated plasma triglyceride
levels, or changes in HDL particle size distribution. In addition,
we are focusing on candidate genes with known roles in metabolic
pathways essential for glucose and lipid homeostasis. We have explored
the haplotype structure of PTPN1, a gene involved in the regulation
of insulin, leptin, and VEGF signaling pathways, and APOA5, a member
of the apolipoprotein gene cluster on human chromosome 11. We have
shown haplotype associations with a diverse range of phenotypes
for both genes in different populations, and are currently investigating
the direct effect of haplotypes on expression and activity levels
of these genes.
In order to facilitate these efforts, we are developing novel
tools and technologies to aid in our endeavors. In collaboration
with the Bioinformatics Research Center, we have developed a novel
web-based tool for the analysis of SNP genotyping data, and are
currently comparing haplotype block analysis algorithms for their
usefulness and compatibility with different datasets. In collaboration
with Dr. L. Smith (UW Madison) and Third Wave Technologies, we
are developing a high-throughput SNP genotyping platform using
microarray technology, and real-time assays for accurate mRNA quantification.
As part of the NHLBI-funded National Proteomics Center (http://proteomics.mcw.edu),
we are developing efficient mass spectrometry-based experimental
approaches to efficiently analyze and quantify the entire cellular
proteome of vascular endothelial cells to identify proteomic changes
during angiogenesis.
Our research efforts are divided into Technology
Development and Biological Applications of these technologies
to the study of human obesity, cardiovascular disorders, insulin
resistance, and dyslipidemias.
Our
laboratory is trying to understand how genetic sequence variation
affects gene function and ultimately human disease. We utilize
genomics tools to discover single nucleotide polymorphisms (SNPs)
by sequencing, genotype these SNPs in large numbers of individuals
to understand patterns of linkage disequilibrium and haplotypes
across extended regions of the human genome, analyze potential
association of SNPs and haplotypes with complex human disorders,
and explore the effect of haplotypes on gene expression and protein
levels.
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