Welcome to the Klein Lab

The Klein Lab is focused on understanding the role inherited genetic variation plays in the development, progression, and outcome of cancer. We see these genetic and genomic studies both as a window into learning about fundamental processes of cancer biology and as a means to develop improved diagnostic and prognostic biomarkers. We are actively engaged in several specific projects towards this end.

  1. GWAS-identified risk alleles and alteration of transcriptional regulation. While genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the risk of developing cancer, for the most part the mechanism by which these alleles increase cancer risk cannot be explained by changes in the amino acid sequence of encoded proteins. Instead, we hypothesize that many of these SNPs alter transcriptional regulatory elements, and therefore the expression of nearby genes. To test this hypothesis, as members of the ENCODE Consortium, we are actively correlating cancer-identified GWAS results with annotations of functional regulatory elements to ask if GWAS-identified SNPs are enriched in regulatory regions in the relevant tissue. We are also conducting expression quantitative trait locus (eQTL) studies to ask if cancer-identified risk alleles are correlated with gene expression changes in the relevant tissue.
  2. Role of SNPs in interpreting PSA levels. Though widespread prostate-specific antigen (PSA) screening has resulted in earlier detection of prostate cancer in the United States, there is much debate to its utility due to the twin harms of false positives resulting in unneeded biopsies and the potential overtreatment of otherwise indolent disease. We have previously observed that many SNPs are associated with levels of PSA and related biomarkers. Through integrated analysis of genetic and biomarker data in several large cohort studies, we are developing novel predictive models that will more accurately predict which men may have prostate cancer and whether the disease is aggressive.