Post-translational modification serves as an important mechanism for modulating the structure, activity and lifetime of many proteins. My laboratory is exploring three distinct projects related to post-translational modification.

1. One project concerns the cellular function of protein L-isoaspartyl methyltransferase, an enzyme that methylates damaged proteins containing atypical isoaspartyl residues. Substantial evidence indicates that this enzyme serves to repair these atypical residues by converting the isopeptide bond to a normal peptide bond. Current research is focused on testing the repair hypothesis in cell culture systems, understanding factors that lead to isoaspartate formation in proteins, determining the medical consequences of PIMT deficiency in humans, and exploring the possibility that high levels of isoaspartate in the extracellular matrix of brain may play a role in development.
   
   
2. A second project concerns the function and substrate specificity of protein methyltransferases that modify arginine in proteins. Arginine methylation appears to play an important role in modulating the interactions of proteins with RNA and DNA. In collaboration with the lab of Dr. Michael Stallcup at USC Medical School, we are currently investigating the role of protein arginine methylation in regulation of gene transcription.
   
   
3. A third line of research concerns the role of protein phosphorylation in regulation of synaptic transmission in the brain. A novel protein (PP59) has been identified that is enriched in the synaptic membrane fraction of the cerebellum and serves as a substrate for the cyclic-AMP-dependent protein kinase. Current studies are focused on determining the cellular and subcellular localization of PP59, and determining its sequence in order to establish homology to proteins or protein domains of known function.