Research Overview

The Smaldino laboratory is interested in G-quadruplex DNA and RNA structures and enzymes that unwind them. G-quadruplexes are "knot-like" provide an essential layers of  replication, transcriptional, and translational control in  healthy cells. However, when in excess or aberrantly unwound, G-quadruplexes can be problematic. 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, 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.