Research Introduction:

We are interested in the underlying genetic basis of human disease. We investigate both Mendelian disorders and common/complex traits. For the past 18 years we have investigated the genetic basis of psoriasis and psoriatic arthritis; complex human diseases of the skin and joints. Our current studies also involve genomic approaches to understanding fundamental mechanisms leading to cancer. To accomplish our goals we perform global genetic and genomic analyses.

To identify causative genetic variants of common disease we perform:

• Genome-wide association studies, follow up studies to identify the causative variant with second generation sequencing (NexGen)
• A search for structural DNA variation predisposing to disease
• Complete re-sequencing of coding sequence (exomes) of patients to identify rare variants

We also perform functional genomic analyses to follow up disease associations. This includes ChIP-Seq; investigation of targets of RUNX1 and RUNX3, transcription factors we have previously shown may be associated with autoimmunity (Helms et al., 2003) and which have been implicated in tumorigenesis. As a follow up to our genetic analyses of the genetic disorder lipodystrophy (Speckman et al., 2000), which leads to absence of body fat, we are examining the molecular pathway of adipocyte differentiation mediated by the seipin protein.

Systems biology: To examine the systems biology of disease states (psoriasis) and cancer (prostate) we are identifying altered mRNAs, and small non-coding RNAs (including microRNAs) and modeling the altered networks of the disease state.

Epigenetic analysis: Effects on the epigenome in disease (psoriasis) are also being investigated with genome-wide methylation studies followed by precise mapping of altered methylation sites.

Washington University School of Medicine, Department of Genetics, Division of Human Genetics
Last updated Aug. 22, 2009