We use biochemical, molecular, immunocytochemical, and behavioral techniques in animal models to address the role that STEP plays in regulating aspects of learning.
Current projects include the involvement of STEP in three disorders: Alzheimer's disease, fragile X syndrome, and schizophrenia.
We are characterizing the STEP knock-out mouse, STEP's regulation of local protein translation, STEP's regulation of glutamate receptor trafficking, as well as screening for STEP inhibitors that are tested in animal models to determine if we can rescue cognitive deficits.
There are currently 4 million individuals suffering from Alzheimer's disease (AD) in the USA, with an annual cost of over $200 billion per year. Although some drugs are currently available to treat AD, none provide more than temporary relief from the relentless progression of cognitive deficits. The discovery of new drugs that improve cognitive function is a critically important area in translational research in AD.
Fragile X syndrome is a developmental disorder that is one of the translational neuroscience projects in the lab. Dr. Susan Goebel-Goody is in charge of this project and is currently writing up her results. The basic hypothesis being tested is that STEP is over-expressed in this disorder. This in turn leads to a disruption of synaptic plasticity and contributes to the cognitive deficits that are present. Here are two review columns on fragile x syndrome written by Marilee Ogren, Ph.D. and myself.
Schizophrenia is the third disorder that is a major focus of the current work in the laboratory. There are two hypotheses being tested in the lab. The first, led by Dr. Nikisha Carty, implicates STEP in mediating the beneficial effects of the neuroleptics used to treat this devastating disorder. The second project, led by Dr. Pradeep Kurup and Dr. Jian Xu, suggests that the loss of ionotrophic glutamate receptors that occurs in schizophrenia is mediated by over-expression of STEP. We are also testing our hypothesis by crossing mouse SZ models with the STEP KO mouse. The prediction is that we will reverse some of the cognitive and psychotic-like symptoms by reducing STEP levels.