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. The initial manuscripts describing this work are being written.
Related projects in search of research leaders:
- What is the mechanism for the increase in STEP protein levels in schizophrenia (microRNAs, disruption of the normal ubiquitination and degradation of STEP)?
- What are the effects of other neuromodulators (e.g., serotonin, acetylcholine, dopamine, nicotine) on STEP expression levels?
- We are currently searching for STEP inhibitors, a project led by Dr. Jian Xu in the lab. We will need to test lead compounds in our SZ animal models.