Kyle Cottrell
Title:
Assistant Professor
PhD Granting Institution:
Washington University in St. Louis
Contact:
Email Address: kacottre@purdue.edu
Office Phone: 765-494-6941
Lab Website Link: https://www.cottrellrna.com/
Primary Training Group:
Cancer Biology
Secondary Training Groups:
Computational and Systems Biology, Microbiology, Immunology and Infectious Diseases
Research Areas:
RNA biology, cancer biology, RNA binding proteins, double-stranded RNA, breast cancer
Current Projects:
Identification of suppressors of dsRNA sensing, Evaluating mechanisms that regulate dsRNA sensing, Targeting PACT and/or ADAR1 in TNBC, Uncovering essential RNA binding proteins in breast cancer
Importance of Interdisciplinary Research:
Breast cancer is the most common form of cancer in American women. Of the many subtypes of breast cancer, the triple-negative subtype is the deadliest. Unlike other subtypes of breast cancer, which are driven by specific proteins, like estrogen receptor positive (ER+) breast cancer, triple-negative breast cancer (TNBC) is not driven by a single protein. This creates a therapeutic challenge. For ER+ breast cancer, clinicians are equipped with multiple therapies that antagonize the estrogen receptor and prevent growth of the tumor. For TNBC, there is no such therapy. Instead, clinicians turn to chemotherapy which broadly targets the ability of the tumor to grow. Those therapies are somewhat indiscriminate and thus inhibit the growth of other rapidly proliferating cells, which causes the side-effects that all too many of us are familiar with. The Cottrell Lab is focused on finding new therapeutic targets for cancers like TNBC, with a primary focus on RNA binding proteins (RBPs). RBPs represent a rich and relatively unexplored set of proteins. There are >1500 RBPs encoded in the human genome, and only a small portion have been well described. To date, most work in the Cottrell Lab has focused on double-stranded RNA (dsRNA) binding proteins (dsRBPs). Many of the several dozen dsRBPs encoded in the human genome have roles in detecting exogenous dsRNAs generally arising from viral infection. These dsRNA sensors are our frontline defense against virus like SARS-CoV-2, however their indiscriminate nature creates a regulatory challenge for the cell. Most dsRNA sensors cannot distinguish between host and viral dsRNAs. To prevent sensing of endogenous dsRNA and activation of innate immunity pathways, several dsRBPs function to suppress dsRNA sensing. In many cancer cells, elevated expression of dsRNA sensors, and dsRNAs themselves, drives sensitivity to depletion of suppressors of dsRNA sensing. The Cottrell Lab has identified three suppressors of dsRNA sensing (ADAR1, DHX9 and PACT) with therapeutic potential in TNBC.