Ageing; Cell growth, differentiation and development; DNA Replication, Recombination and Repair; Gene Expression; Molecular and Cellular Biology; Signal Transduction; Stem Cells; Transcription Factors
The main goal of my research group is to understand the role of N-terminal methylation in human development and disease. I identified the first eukaryotic N-terminal methyltransferases, NRMT1 and NRMT2, and am now working to identify how these enzymes affect cancer development and ageing. Our laboratory has shown that NRMT1 functions as a tumor suppressor in mammary glands, and its loss sensitizes breast cancer cells to DNA damaging chemotherapeutics. We have also created the first NRMT1 knockout mouse and shown it to have developmental defects, as well as exhibit phenotypes of premature ageing, including neurodegeneration and cognitive impairment. We hypothesize that these premature ageing phenotypes may result from misregulation of different stem cell populations, as we have recently shown that loss of NRMT1 alters both muscle and neural stem cell differentiation. Currently, we are working to understand the exact biochemical pathways that lead from loss of N-terminal methylation to these phenotypes. We are also studying how post-translational modifications on the N-terminus of proteins may interact and dictate protein function, similar to the post-translational modifications found on histone tails.