Current research focus

My main area of interest is in determining changes in protein protein interactions in a 6-hydroxydopamine model of Parkinson's disease (PD). I am interested in how post-synaptic signaling changes in the striatum after dopaminergic projections from the substantia nigra are lost. My particular area of interest focuses on altered protein:protein interactions between calcium/calmodulin-dependent protein kinase II (CaMKII) and other porteins as well as between protein phosphatase 1 (PP1) and its regulatory subunits.

CaMKII and PP1 play opposing roles by their function as a kinase and a phosphatase, respectively. Kinases are proteins that modulate the activity of other proteins by adding a phosphate group to that protein. The target protein is referred to as a substrate. There are many known substrates for CaMKII, all of which are phosphorylated on a serine or threonine residue. Some important substrates for CaMKII include the ionotropic glutamate receptors. PP1 is a protein phosphatase. Phosphatases, as opposed to kinases, remove phosphate from a protein. PP1 is a serine/threonine phosphatase so it removes phosphates that are located on serines and/or threonines. PP1 has many different substrates unlike CaMKII which has a much more limited number of substrates. Therefore, its activity must be more tightly regulated. this regulation is achieved by regulatory proteins. These regulatory proteins can bind to PP1 and inhibit its ability to dephosphorylate proteins. In addition, some regulatory proteins can bind to PP1 and target it to different parts of the neuron, thereby directing its activity to specific locations. CaMKII can also bind to various regulatory proteins that alter its localization and/or activity; however the number is much less that the PP1 binding proteins. CaMKII associated proteins are known as CaMKAPs.

Other areas of interest

In addition to PD, I am very interested in how CaMKIIAPs are altered in Angelman syndrome (AS). AS is a disorder that is caused by an alteration of the maternal UBE3A gene. People with AS have an ataxic (uncoordinated) gate, develop very little vocabulary, can have seizures when young, and have an overwhelmingly contagious happy disposition.