The completed sequence of the human genome is leading to increased knowledge regarding variation among individuals and how this variation may contribute to disease susceptibility. As a species, Homo sapiens are 99.9% identical at the genomic DNA level. The 0.1% difference (or ~3,000,000 basepairs), however, is important because it will likely explain why one individual is more (or less) susceptible to disease. To date, most of the known, disease-causing genetic variations are caused by variants in single genes that tend to have a big impact on health, making genetic contributions to the illnesses relatively easy to find. The more common, complex diseases, such as cancer, diabetes, and autoimmunity, however, present a much tougher challenge. These diseases are likely to be caused by genetic variations in many genes that together increase the risk of disease. Environmental and other non-genetic factors may also contribute to these disease processes.

Gene expression profiling is first used to identify those genes whose expression profile is different between sample sets (e.g., affected vs. un-affected, responder vs. non-responder). Using high-throughput genotyping, these datasets are then mined for sequence variations associated with the gene's expression level. Finally, these genes are evaluated as potential diagnostic, prognostic, and therapeutic markers.

Research and scientific development within the laboratory involves three general areas of focus:

1) Molecular characterization of genomic DNA sequence variants associated with BIOLOGICAL processes. Research and development in this area focuses on the elucidation of the genes involved in biological processes especially those relevant to disease susceptibility. Response or lack thereof to genotoxic agents, for example, may determine which individuals are more (or less) susceptible to disease. Similarly, elucidation of the genomic DNA sequence variations in genes involved in response to drug treatments may be used to stratify those individuals who ultimately go onto respond to treatment from those who do not.

2) Intra- and inter-population specific expression profiles and identification of associated genomic DNA sequence variants. Research and development in this area seeks to utilize the natural genetic variation amongst the worlds populations to identify genomic DNA sequence variations that alter a genes function and ultimately susceptibility to disease. Moreover, research in this area is likely to uncover why some diseases disproportionately, and sometimes uniquely, affect a single population.

3) Molecular characterization of genomic DNA sequence variants associated with DISEASE processes. Research and development in this area focuses on the identification of genes and genomic DNA sequence variations unique to specific disease processes. Research in this area has already uncovered unique expression profiles for several diseases. The genes contained within these profiles are ideal candidates for containing sequence variations that alter susceptibility to disease.

In summary, research within my laboratory strives to better understand human genetic variation as it relates to disease susceptibility and ultimately treatment of disease.