The Contractor Lab

Research Topics

Fragile X Syndrome

Fragile X syndrome is the most common inherited form of mental impairment, affecting approximately 1 in 4000 males and 1 in 8000 females. In addition to intellectual disability, children with FXS exhibit behavioral problems, sensory hypersensitivity, language delay, and as many as 30% also have autism or autistic traits. The disease is caused by a CGG trinucleotide repeat expansion in the 5’ untranslated region of the FMR1 gene, which leads to its transcriptional silencing and loss of the Fragile X Mental Retardation Protein (FMRP). FMRP has important roles in translational control of a large number of messenger RNAs, many of which encode for synaptic proteins. The resultant dysregulated expression of many proteins involved in synaptic development causes major disruptions in synapse maturation and experience-dependent wiring of brain circuits.

Members of the Contractor laboratory have been studying the disorder using the mouse model of the Fragile X; Fmr1 KO mice. We have demonstrated that there are shifts in critical periods (link to Harlow paper) in sensory regions of the developing cortex which are characterized by changes in both glutamatergic (Link to Harlow et al) and GABAergic (Link to He et al 2016) synaptic signaling. There are also delays in the developmental properties of interneuron (link to Nomura paper) subtypes which are important for cortical development. Our ultimate goal is to understand the physiological and functional disruptions that occur during cortical development and determine whether we can target key mechanisms to normalize and rescue (link to He et al 2019) these deficits in mice, and thus specify potential molecular targets for the development of therapies.

Other Areas of Interest

Synaptic Mechanism

Autism Spectrum Disorders

Affective Disorders