Whitehead Fellow

Olivia
Corradin

Olivia Corradin

Scott Cook and Signe Ostby Fellow, Whitehead Institute

617.324.6481
corradin@wi.mit.edu

Corradin
publications

One of the primary goals in the field of genetics is to identify genetic variants that contribute to disease heritability. Elucidating the functional consequence of genetic variants associated with disease provides essential insights into the molecular mechanisms that define human traits. However, this is complicated by the fact that a preponderance of disease-associated genetic variation lies outside of protein-coding genes. Rather than modify protein structure and function, these noncoding variants frequently impact regulatory elements and thereby alter the quantitative and spatiotemporal regulation of gene expression.

The regulation of gene expression is critical for establishing and maintaining the diverse cell types of the human body. Genes with critical cellular functions are frequently regulated through a circuit involving multiple regulatory elements that are brought within physical proximity by DNA folding. These complex regulatory circuits are hotspots for genetic predisposition to disease  In order to interpret the genetic variation that lies in these regions, it is essential to understand of how multiple regulatory elements cooperate to control target gene expression.

Our aim is to elucidate the role of noncoding DNA variants in defining human disease pathogenesis and susceptibility. We address this goal through functional studies of the mechanisms by which multiple regulatory elements collude to define gene expression and by utilizing 3-dimensional DNA organization to evaluate patient genetic data. Our goals are 4-fold: (1) enable the interpretation of noncoding variants by determining their functional consequences, (2) reveal the dynamics of enhancer-gene regulation that influence disease pathogenesis, (3) identify the clinical risk associated with gene regulatory circuit variation, and (4) aid in the translation of disease-association into insights that benefit patient diagnosis, treatment and preventive care.

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