Paul J Mathews
Assistant Professor-in-Residence, Neurology, University of California Los Angeles
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.
- Perez H, Abdallah MF, Chavira JI, Norris AS, Egeland MT, Vo KL, Buechsenschuetz CL, Sanghez V, Kim JL, Pind M, Nakamura K, Hicks GG, Gatti RA, Madrenas J, Iacovino M, McKinnon PJ, Mathews PJ. A novel, ataxic mouse model of ataxia telangiectasia caused by a clinically relevant nonsense mutation.. eLife, 2021.
- Choe KY, Sanchez CF, Harris NG, Otis TS, Mathews PJ. Optogenetic fMRI and electrophysiological identification of region-specific connectivity between the cerebellar cortex and forebrain.. NeuroImage, 2018.
- Ekins S, Mathews P, Saito EK, Diaz N, Naylor D, Chung J, McMurtray AM. α7-Nicotinic acetylcholine receptor inhibition by indinavir: implications for cognitive dysfunction in treated HIV disease.. AIDS (London, England), 2017.
- Ekins S, Diaz N, Chung J, Mathews P, McMurtray A. Enabling Anyone to Translate Clinically Relevant Ideas to Therapies.. Pharmaceutical research, 2016.
- Lee KH, Mathews PJ, Reeves AM, Choe KY, Jami SA, Serrano RE, Otis TS. Circuit mechanisms underlying motor memory formation in the cerebellum.. Neuron, 2015.
- Mathews PJ, Lee KH, Peng Z, Houser CR, Otis TS. Effects of climbing fiber driven inhibition on Purkinje neuron spiking.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012.
- Otis TS, Mathews PJ, Lee KH, Maiz J. How do climbing fibers teach?. Frontiers in neural circuits, 2012.
- Mathews PJ, Jercog PE, Rinzel J, Scott LL, Golding NL. Control of submillisecond synaptic timing in binaural coincidence detectors by K(v)1 channels.. Nature neuroscience, 2010.
- Scott LL, Mathews PJ, Golding NL. Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010.
- Scott LL, Mathews PJ, Golding NL. Posthearing developmental refinement of temporal processing in principal neurons of the medial superior olive.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005.
- Mathews PJ. Respiratory care.. Nursing, 2005.
- Mathews PJ, Al-Jasser T, Weltman C, Rokosz M. The latest in respiratory care.. Nursing management, 2005.
- Mathews PJ, Roark-Sample B, Schmidt J, Brooks K. The latest in respiratory care.. Nursing management, 2004.
- Mathews PJ, Wilcoxon S, Chung A, Younger B, Banks C, Cranford T. The latest in respiratory nursing.. Nursing management, 2003.
- Mathews PJ. Co-oximetry.. Respiratory care clinics of North America, 1995.