Nicole Fisher

Graduate Student, Pharmacology

I am a pharmacology graduate student co-mentored by Dr. Colleen Niswender and Dr. Jeff Conn within the Vanderbilt Center for Neuroscience Drug Discovery.  Our research focuses on evaluating metabotropic glutamate receptors (mGlus) as novel therapeutic targets for the treatment of MeCP2-related disorders. Methyl-CpG-binding protein 2 (MeCP2) is a transcription factor that is critical for proper brain function.  A loss-of-function mutation in the MeCP2 gene leads to Rett syndrome, a severe neurodevelopmental disorder that primarily affects females. Rett syndrome patients develop normally for 6-18 months, but then undergo a sudden regression in which they lose acquired speech, social skills, and purposeful use of their hands. They further develop stereotyped hand-wringing movements, intellectual disability, motor abnormalities, seizures, and respiratory apneas.  In 2005, it was discovered that an extra copy of the MeCP2 gene produces a similar disorder, now called MECP2 Duplication syndrome.  Studies in mouse models of these disorders suggest that the underlying pathologies are reversible, even in adult animals.  mGlus are widely expressed in the brain, and act as important regulators of synaptic transmission and plasticity.  Using allosteric modulators that alter the activity of specific mGlu subtypes, we aim to normalize physiology and behavior in mouse models of MeCP2-related disorders.

My clinical mentor is Dr. Sarika Peters, a clinical psychologist within the Vanderbilt Kennedy Center. Dr. Peters conducts clinical studies to better characterize the progression of MeCP2-related disorders and to identify potential biomarkers. During my clinical hours with Dr. Peters, I have the invaluable opportunity to interact with Rett syndrome and MECP2 Duplication syndrome patients.  These interactions provide me with a deeper understanding of clinical symptoms and the burden that theses symptoms place on the everyday lives of patients and their caretakers. They also inspire new directions in my research, and motivate me to focus on studies that are likely to translate from mouse models to humans.