| Tom Otis | |
| Occupation: | Academic, researcher, author |
| Education: | B.S., Biological Sciences M.S., Biological Sciences Ph.D., Neuroscience |
| Alma Mater: | Stanford University |
| Workplaces: | University College London |
Tom Otis is an American researcher, academic and author. He is the Chief Scientific Officer at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour and holds a Professorship in Neuroscience at University College London.[1]
Otis' research has been focused on cellular and circuit function of the cerebellum and hippocampus, as well as preclinical models of spinocerebellar ataxia and amyotrophic lateral sclerosis.[2]
Otis received a B.S. and an M.S. in Biological Sciences in 1988 from Stanford University. He continued his education at Stanford University, where he received a Ph.D. in neuroscience in 1993.[3] Otis’ doctoral work was completed in the laboratory of Istvan Mody at Stanford University and focused on fundamental aspects of inhibitory synaptic transmission. Using newly developed methods for patch clamping in brain slice preparations, Otis characterized the function of GABA-gated ion channels (GABAA receptors) and GABA activated G protein coupled receptors (GABAB receptors).[4]
In 1998, Otis joined University of California, Los Angeles as an Assistant Professor, becoming Associate Professor in 2003 and Full Professor in 2007. He became the Edith Agnes Plumb Endowed Chair in Neurobiology at UCLA in 2013.[5] He served as the Vice Chair of Department of Neurobiology at UCLA Medical Center from 2008 to 2013, and then as the Chair of the Neurobiology Department from 2013 to 2015. From 2010 to 2014, he was the Vice Chair of Interdepartmental Graduate Program in Neuroscience at UCLA.[6]
Otis took the position of Vice Director and Section Head of F. Hoffman-La Roche in 2015 while on leave of absence from UCLA. In 2017, Otis left Roche and moved to the United Kingdom, where he joined University College of London as a Professor of Neuroscience[7] and the Sainsbury Wellcome Centre for Neural Circuits and Behaviour as Chief Scientific Officer.[8]
In postdoctoral work with Laurence Trussell at the University of Wisconsin, Madison, Otis studied excitatory synaptic transmission, measuring glutamate receptor activation at a giant synapse in the chick auditory brainstem and constructing models of neurotransmitter diffusion and receptor gating that explain how glutamate interacts with postsynaptic receptors.[9] In postdoctoral work with Craig Jahr and Mike Kavanaugh, he used electrophysiological approaches and fast solution exchange to detail the biophysical function of glutamate transporters (the proteins responsible for removing glutamate from excitatory synapses).[10]
In his own laboratory at UCLA, Otis extended this work to describe how glutamate transporters shape excitatory signals to different pools of glutamate receptors. He hypothesized that a feedback loop between G protein coupled glutamate receptors and glutamate transporters might regulate ‘spill over’ of glutamate from synapses, thereby ensuring that excitatory synapses remain independent.[11]
Otis' laboratory also characterized the pharmacology of certain subtypes of GABAA receptors that are located extrasynaptically. In collaboration with the laboratory of Richard Olsen, he presented evidence that ethanol enhances these subtypes of GABAA receptors and that this likely contributes to the intoxicating and sedative effects of alcohol.[12]
A main line of Otis' work has been directed at understanding how cerebellar circuits are involved in coordinating complex movements. Using optogenetics to manipulate cerebellar circuits, Otis showed that robust but artificial associative memories can be imparted such that otherwise innocuous sensory stimuli can then generate aberrant movements. These findings validate circuit-based models of cerebellar learning and suggest that learning may involve modifications at multiple sites in the cerebellar circuit.[13]
In collaboration with the lab of Stefan Pulst, Otis’ team has characterized and studied mouse genetic models of spinocerebellar ataxia type 2. Working with scientists at IONIS, the teams developed an antisense oligonucleotide targeting the SCA2 gene and showed that this molecule improves motor function in mice. Due to the involvement of SCA2 in stress granules in degenerating neurons, the same antisense oligonucleotide against SCA2 has potential to treat other misfolded protein disorders such as amyotrophic lateral sclerosis and frontotemporal dementia.[14]