Research Area 1: Understanding how N-terminal methylation governs stem cell fate
Recent work from our lab has uncovered a role for N-terminal methylation in both neural and muscle stem cell fate. In the brain, loss of NRMT1 leads to depletion of the neural stem cells pools and subsequent neurodegeneration. In muscle, loss of NRMT1 leads to altered stem cell differentiation. Future projects will aim to better understand the molecular mechanisms behind these phenotypes and identify other types of affected stem cells. These studies are done in a combination of mouse and tissue culture models.
Research Area 2: The role of N-terminal methylation in cancer biology
We have also shown that N-terminal methylation can either promote or inhibit cancer progression, depending on the cellular context. In breast cancer, NRMT1 acts as a tumor suppressor, but in cervical and colon cancers, NRMT1 acts as an oncogene. We believe these differences are substrate dependent. Future projects aim to better understand the signaling pathways to which NRMT1 contributes in different cancer types. These studies are primarily done in tissue culture models.
Research Area 3: Biochemistry of N-terminal methylation
Another main focus of our lab is determining how NRMT1 is regulated. We have shown that transcriptionally, NRMT1 expression is regulated by the CREB1 transcription factor. We have also shown that NRMT1 enzymatic activity is differentially regulated by binding of its close homologs NRMT2 and METTL13. Future projects in this area include identification of additional binding partners, determination of cellular compartmentalization, and characterization of NRMT1 post-translational modifications. We are also interested in the interplay between N-terminal methylation and other modifications on the N-termini. These studies are done in a combination of tissue culture and in vitro models.