Research Overview

The Smaldino laboratory is interested in G-quadruplex nucleic acid structures and enzymes that unwind them. G-quadruplexes are stable, ‘knot-like’ structures that form within guanine (G)-rich regions of DNA or RNA. These structures provide an essential layer of transcriptional and translational regulation in a healthy cells. However, when in excess or aberrantly unwound, G-quadruplexes can become pathological. We focus our efforts on studying the major human G-quadruplex helicase DHX36 (aliases: G4R1 and RHAU) which is a major "undoer of G-quadruplex knots".

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We apply our expertise in G-quadruplex and DHX36 biology to study G-quadruplex-linked diseases including, C9ORF72-linked ALS and frontal temporal dementia, and cancer. We leverage a combinatorial approach of biochemical assays, human cell culture, and mouse models to study these topics. Our long term goal is to develop and implement strategies to target DHX36 for the treatment of disease.