Marcelo A. Nobrega, MD, PhD
My research interests include the mechanisms by which genes are regulated in space and time by distant regulatory elements and the functional impact of genetic variation in these regulatory elements. We align these interests with the observation that the genetic architecture underlying most common polygenic human disorders involve noncoding genetic variation, many of which presumably altering the function of distant regulatory elements. From this perspective, we have developed novel in vivo and genomics technologies to identify cis-regulatory sequences in the human genome and test the impact of regulatory variants on gene expression and disease etiology. Aided by these technologies, we have characterized genetic networks leading to heart diseases; implicated regulatory variants in the etiology of congenital heart diseases; demonstrated how common variants within enhancers increase risk to prostate cancer; characterized the downstream functions of genes associated with type 2 diabetes and obesity. Recently I have also become interested in defining the role of 3D nuclear organization on gene regulation and the impact of genetic variation on the 3D interactions between genes and distant regulatory elements. The overarching goal of my research is to integrate genetics, genomics, and in vivo experimental approaches to understand how genotypic variants in regulatory DNA relates to phenotypic variation and human diseases.