Member, Whitehead Institute

Olivia Corradin

The Corradin Lab studies genetic variants — regions of DNA that differ from person to person — and how they are associated with human disease.

Image
Olivia Corradin stands smiling at a lab bench.

455 Main Street
Cambridge, MA 02142
United States

617.324.6481

Achievements & Honors

NIH Director’s Pioneer Award: Avenir Award Program for Genetics or Epigenetics of Substance Use Disorders 2017
American Society Human Genetics Annual meeting program committee member 2016-2019
Doctoral Excellence in Genetics Award, Case Western Reserve University 2015

Affiliations

Scott Cook and Signe Ostby Fellow, Whitehead Institute

Question

How do genetic variants contribute to disease?

Approach

Understanding 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 Corradin Lab is working to uncover the role of noncoding DNA variants in defining human disease pathogenesis and susceptibility. They address this goal through functional studies of the mechanisms by which multiple regulatory elements collude to define gene expression and by utilizing three-dimensional DNA organization to evaluate patient genetic data. Their goals are four-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.

The Corradin lab leverages the complexity of gene regulation in order to aid the interpretation of genetic variation that contributes to human disease. The lab has developed an approach which utilizes the three-dimensional organization of chromatin to assess the contribution of genetic variants to disease risk. This approach evaluates variants that are physically linked to the same target gene cooperatively, without assumption of additivity. This allows the researchers to assess all of the regulatory elements that control a gene within a given cell type for contribution to disease risk. They then utilize these results to identify the cell type in which dysregulation of the target gene contributes to disease risk. In studies of multiple sclerosis, this new approach increases total heritability identified by three- to five-fold. The method has yielded several unexpected predictions such as risk loci that act through dysregulation of gene expression in oligodendrocytes, rather than T cells.

Another area of Corradin’s research focuses on addiction to opioids and substance abuse disorders, some of the most urgent public health crises in the US. Eight to 10 percent of individuals prescribed an opioid develop opioid use disorder. Genetics plays a major role in defining this variability. Opioid addiction is estimated to be 60 percent heritable, however the variants and genes that define this heritability have remained elusive. Delineating the genes, pathways, and cellular phenotypes that define risk to  substance abuse disorders is critical to furthering our understanding of these disorders. The lab combines post-mortem tissue studies with iPS-derived astrocytes, microglia, oligodendrocytes and dopaminergic neurons to further our understanding of the genetic and epigenetic variation that contributes to susceptibility to substance abuse disorders.
 

Bio

Corradin graduated with a bachelor’s of science in biochemistry from Marquette University where she worked with Dr. Edward Blumenthal. In 2011, she joined the lab of Peter Scacheri at Case Western Reserve University. Her thesis work focused on the study of genetic and epigenetic dysregulation of gene expression in human disease. Corradin joined Whitehead Institute as a Fellow in July 2016, and became an Institute Member and MIT Associate Professor of Biology in 2021. Outside of the lab, Corradin is most likely to be found at a local dance studio continuing her love of ballet and contemporary dance.

 

Selected publications

Daniel C Factor, Anna M Barbeau, Kevin C Allan, Lucille R Hu, Mayur Madhavan, An T Hoang, Kathryn E A Hazel, Parker A Hall, Sagar Nisraiyya, Fadi J Najm, Tyler E Miller, Zachary S Nevin, Robert T Karl, Bruna R Lima, Yanwei Song, Alexandra G Sibert, Gursimran K Dhillon, Christina Volsko, Cynthia F Bartels, Drew J Adams, Ranjan Dutta, Michael D Gallagher, William Phu, Alexey Kozlenkov, Stella Dracheva, Peter C Scacheri, Paul J Tesar, Olivia Corradin