Gene expression levels are precisely regulated during development; quantitative perturbations to this process are a frequent cause of both rare and common human disease. However, most experimental tools that have been applied to study gene function are binary in nature. Therefore, the overarching goal of the Naqvi Lab is to develop and apply tools to quantitatively perturb gene regulation to understand both basic mechanisms of gene regulation and how this goes awry in disease.
Transcription factors (TFs), proteins that bind to noncoding regulatory DNA such as enhancers and promoters and modulate the production of RNA from target genes, are key drivers of developmental regulatory programs. TFs are highly dosage-sensitive; quantitative changes of 50% or less in TF levels frequently cause rare disorders or common trait variation. We are using cutting-edge tools to precisely modulate TF dosage and build quantitative, predictive models of how TF dosage impacts molecular, cellular, and morphological phenotypes, with the goal of identifying the regulatory elements, genes, and cell states that are most sensitive to TF dosage and thus drivers of disease.
To learn more about the Naqvi Lab, please visit naqvilab.org.
