Dr. Mathews’ research program seeks to understand how neural communication between brain regions, in particular the cerebellum and forebrain gives rise to complex animal behavior. Our current research goals are to 1) define region-specific connectivity between the cerebellum and forebrain, 2) elucidate the neural influence the cerebellum has on downstream forebrain structures (e.g. basal ganglia and prefrontal cortex), and 3) to elucidate the neural information provided by the cerebellum to the forebrain in non-motor behaviors (e.g. reversal learning). The lab currently incorporates a multifaceted set of approaches to answer these questions including in vivo multi-electrode recordings, functional Magnetic Resonance Imaging (fMRI), function Ulrasound (fUS), and animal behavioral testing and anatomy. Furthermore, we are complementing these approaches with both directed (e.g. DREADD or optogenetic manipulation) and/or disease related (e.g. mouse models of autism) disruptions in cerebellar-forebrain communication to significantly advance our understanding of cerebellar-forebrain communication and its role in non-motor behavior.
A second major component of our research program is to understand and devise potential treatments for the disease Ataxia-Telangiectasia (A-T). To do so, we have recently created a new mouse model of A-T that for the first time displays the phenotypical loss of motor control and contains a human related genetic mutation (i.e. nonsense mutation). With this new model we are elucidating the neuropathogenesis of the disease and testing a new small molecule therapeutic designed to read-through premature termination codons. In collaboration with others here at the Lundquist Intistute, we are further testing and developing the therapeutic potential of these small molecule read-through (SMRT) compounds along with combinatorial approaches to restore protein production in an array diseases caused by a premature stop codons.