Sheryl Anne Vermudez

Chaminade University of Honolulu

Colleen Niswender and P. Jeffrey Conn lab

Rett syndrome (RTT) and MeCP2 duplication syndrome (MDS) are monogenic intellectual disability disorders caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene that result in an under- and over-expression of MeCP2 protein, respectively. Although targeting the modulation of MeCP2 expression seems reasonable, it is therapeutically challenging as a 1x over- and under-expression of MeCP2 can evoke adverse effects. To combat this narrow therapeutic window, the Niswender/Conn lab focuses on the pathway involving metabotropic glutamate receptors (mGlus), one of the downstream targets of MeCP2 and a modulator of synaptic plasticity, a physiological correlate of learning and memory. My project will involve the study of one mGlu receptor, mGlu3 and its role in cognitive deficits that are associated with RTT and MDS. Given our preliminary findings in the lab that mGlu3 expression is proportionally correlated to MeCP2 expression, I hypothesized that modulating mGlu3 function using allosteric modulators has the potential to validate mGlu3 as a potential therapeutic target for cognitive phenotypes observed in MECP2-associated disorders.