Current Research and Scholarly Interests
One of the most daunting challenges in medicine is the complex nature of most diseases (including cancer, diabetes, heart disease and some forms of rare disease) due to interactions between multiple genetic variants and environmental influences. Our research is directed at understanding such complex traits; to do so, we develop novel genomic approaches to investigate the molecular processes that link genotype to phenotype, identify the causal underlying factors, and quantify their contributions. We investigate variation at the level of the genome, transcriptome and proteome, which we integrate with higher-level phenotypes. We also use the resulting molecular networks to predict and evaluate intervention points that enable modulation of phenotype. In particular, our projects are in the following areas:
1) Functions and mechanisms of gene regulation
We have developed several technologies to characterize and quantify pervasive transcription at the genome-wide level as well as its functional impact. In particular, we are interested in the function and regulation of non-coding RNAs, antisense transcription, and the molecular phenotypes that arise from transcriptome complexity.
2) Systems genetics
We have also piloted new technologies to dissect the genetic basis of complex, multifactorial phenotypes. We are interested in studying how genetic variation is inherited through recombination, the consequences of genetic variation, learning to predict phenotype from genotype, and integrating multiple layers of molecular data in order to define intervention points that can be targeted to modulate phenotypes of interest.
3) Disease models
We have used multiple model systems, primarily yeast and human cells, to characterize the genetic and cellular systems affected in particular diseases and assess potential therapeutic strategies. We are studying diseases in patient-derived cells using systematic, followed by mechanistic approaches, to unravel mechanisms and discover novel treatments.
Notably, we place a strong emphasis on the development of new technologies, leveraging the Stanford Genome Technology Center's strengths in this area. Some engineering applications we aim to develop include novel biosensors for detection of minute quantities of biological material and single-cell approaches to investigate genome and transcriptome complexity. Through developing such technologies, we will work with the Center to reduce the cost and increase the accuracy and throughput of biomedical research and health care. Ultimately, we strive to develop approaches that will enable personalized, preventive medicine.
