Kirk L. West, Ph.D.

The genome is a blueprint for the development of an organism that requires multiple mechanisms to protect it from damage. There are multiple types of DNA damage, ranging from DNA lesions that block transcription and replication, mismatched nucleotide bases leading to direct mutagenesis, and single-strand or double strand breaks that can result in loss of genetic material. Organisms have developed multiple pathways that can sense and repair these damage events to protect the genome. These DNA repair response (DDR) pathways establish a interesting balance where the dysregulation of DDR pathways can lead to cells becoming prone to mutation and genetic rearrangement which can lead to carcinogenesis. However, those same cells can then be treated with chemotherapies targeting the DDR pathways and cause the cancer cells to be overwhelmed with DNA damage events. Unfortunately, DDR pathways have evolved to have overlap between the different processes and tumors can develop chemoresistance.

The goal of our research is to combine biochemical and biophysical methods with molecular and cellular biology tools to understand the mechanisms of DNA repair to better understand how and why chemoresistance develops. By better understanding the DDR pathways at a mechanistic level, we hope to prevent and overcome the development of chemoresistance. We are currently investigating the role of the serine/threonine kinases, Tousled-like Kinase 1 and 2, in the DNA damage response.