Elucidating the determinants of aggressiveness in lethal prostate cancer may stimulate therapeutic strategies that improve clinical outcomes. We used experimental models and clinical databases to identify GATA2 as a regulator of chemotherapy resistance and tumorigenicity in this context. Mechanistically, direct upregulation of the growth hormone IGF2 emerged as a mediator of the aggressive properties regulated by GATA2. IGF2 in turn activated...

Drug repositioning is an important component of therapeutic stratification in the precision medicine paradigm. Molecular profiling and more sophisticated analysis of longitudinal clinical data are refining definitions of human diseases, creating needs and opportunities to re-target or reposition approved drugs for alternative indications. Drug repositioning studies have demonstrated success in complex diseases requiring improved therapeutic...

In the past decade there has been an explosion in genetic research that has resulted in the generation of enormous quantities of disease-related data. In the current study, we have compiled disease risk gene variant information and Electronic Medical Record (EMR) classification codes from various repositories for 305 diseases. Using such data, we developed a pipeline to test for clinical prevalence, gene-variant overlap, and literature presence...

Advances in molecular profiling and sensor technologies are expanding the scope of personalized medicine beyond genotypes, providing new opportunities for developing richer and more dynamic multi-scale models of individual health. Recent studies demonstrate the value of scoring high-dimensional microbiome, immune, and metabolic traits from individuals to inform personalized medicine. Efforts to integrate multiple dimensions of clinical and...