Dr. Yousin Suh’s laboratory uses novel technology to investigate the genetic components of aging and aging-related disease using functional genomics approaches, focusing on the identification of gene sequence variation (i.e. single nucleotide polymorphisms (SNPs)), in candidate genes and the assessment of their potential functional impact on aging-related phenotypes. The assessment of the functional impact of SNP haplotypes in vitro and animal models is essential to confirm the link between genotype and phenotype in aging studies.
Dr. Suh’s current and future investigations focus on the following areas:
- Somatic growth and aging: Identification of functional SNP haplotypes of genes involved in the Growth Hormone/Insulin-like Growth Factor-1 (GH/IGF-1) pathway. Genetic and biochemical results from Dr. Suh’s lab indicate that partial loss-of-function mutations in genes acting in the GH/IGF pathway are overrepresented in centenarians relative to controls, which is the strongest evidence to date for a role of this pathway in modulation of human lifespan (Procs Natl Acad of Sci. 2008). She will continue to screen for novel functional mutations in the GH-IGF-1 signaling pathway in centenarians and their offspring.
- Genetic instability and human aging: Using a longitudinal study of the longevity cohort and an aging cohort of Mexican Americans and European Americans, her lab is testing the hypothesis that genetic variation at loci involved in genome maintenance mechanisms can be related to individual differences in the rate and severity of aging-related phenotypes. Functional assays of allelic gene variants positively associated with phenotypes will provide insight into the biological significance of genome maintenance in aging.
- Genomic instability in models: Dr. Suh is also studying mouse models that harbor human gene variations in DNA repair/genome maintenance and as a consequence manifest premature aging phenotypes (Antioxidants & Redox Signaling. 2006). Results from transcriptome analysis delineate a complex genetic network of cellular responses to endogenous DNA damage and suggest it as the cause of the premature aging phenotypes in these mice.
- Haplotype and risk for cancer: Dr. Suh has initiated a population-based association study to test genotype-phenotype correlations of genome maintenance genes in a breast cancer cohort using a comprehensive screening method. She is testing the hypothesis that these rare combinations of common SNPs give rise to BRCA1 gene variants with suboptimal function of the encoded gene products, which may lead to susceptibility to breast cancer.