Research

Our long-term goal is to study fundamental mechanisms of gene expression processes in relation to human diseases and utilize this work to develop novel therapeutic strategies. In our lab, we are adapting novel tools to study the roles of repeat RNA-associated toxicity in a group of neurodegenerative disorders commonly known as ‘Repeat expansion disorders’. We seek to identify novel RNA-binding proteins (RBPs) that interact with expanded repeat RNAs, determine the in vivo structures of different RNA repeats, and then combine these two datasets to determine how specific RBPs facilitate the translation of these disease-causing ‘toxic’ RNAs. Additionally, we want to understand how alterations in fundamental aspects of RNA homeostasis may contribute to human diseases, which include but are not limited to neurodegenerative disorders. We are also interested in the basic mechanism of translational regulation, particularly focusing on the non-canonical translations across multiple domains of life.Our current research is focused on the following areas – 

A. Molecular Mechanisms Underlying Repeat Expansion Disorders

I. Develop/utilize cutting-edge techniques to detect RNA-protein interactions. Define the subcellular and context-specific repeat RNA-protein interactome. Characterize the roles of disease associated RBPs in fly and neuronal models of repeat expansion disorders 

II. Develop/utilize chemical, mutational, and sequencing-based techniques for the analysis of multiple disease-associated repeat RNA structures. Determine how RNA structure/ folding may contribute to translational regulations. Use the RNA structural information to develop/screen for chemical inhibitors of repeat RNA associated toxicity

III. We are interested in employing novel molecular chaperones (such as serine-rich chaperone protein 1 or, SRCP1 from Dictyostelium discoideum) to directly counter toxic aggregation-prone repeat peptides produced through translation of repeat RNAs

B. Regulation of Non-canonical Translations

Canonical translation requires the universal AUG start codon to initiate. However, the use of non-AUG codons (such as GUG, CUG etc) is also widespread in many organisms. We are interested in using computational, molecular, and biochemical approaches to understand mechanisms and regulation of non-AUG translation across multiple domains of life.