Martin L Doughty
Education1995 Ph.D. in Pysiology, University College London, United Kingdom
1990 BSc with honours in Biological Sciences, Birmingham, United Kingdom
BiographyI have broad research interests in animal and cell culture models of neurodevelopment and trauma.
My Ph.D. training was in the Department of Physiology at the University College London, England investigating cerebellar development in spontaneous ataxic mutant mouse models using classical histochemistry and electron microscopy.
I continued my interest in cerebellar development as a Royal Society and then European Community Postdoctoral Fellow at the Pierre et Marie Curie Universite in Paris, France.
I then broadened my research experience at The Rockefeller University, New York, first as a Postdoctoral Fellow and later as a Research Assistant Professor, to include the creation and application of transgenic and targeted mutant mouse models to study neurodevelopment.
As a member of the USU faculty my research has focused on the use of pre-clinical mouse models and human induced pluripotent stem cells to model the pathophysiology of neurotrauma and neurodevelopmental disorders.
Current research in my laboratory focuses on two topic areas: one, the identification of novel spatiotemporal features of molecular pathology following a traumatic brain injury (TBI); two, the use of induced pluripotent stem cells and CRISPR/Cas9 editing to model the neurodevelopmental disorder Angelman Syndrome in human cellular systems.
Molecular pathology following a traumatic brain injury.
In collaboration with genomics and bioinformatics experts within my department, my laboratory is applying state-of-the-art spatial and single cell transcriptomic approaches to well characterized open- and closed-head TBI mouse models of mild contusion injury to identify the molecular pathologies of trauma. Our data identifies distinct white and grey matter molecular features post-injury that are a current research focus. (1) We are investigating the role of peripheral immune cell signaling on the evolution of glial subpopulations in vulnerable white matter (WM) post-injury. This project is based on preliminary data identifying WM glial cell states in TBI mice that have been reported in mouse models of neurodegenerative disease such as Alzheimer’s disease (AD). Our hypothesis is that CNS damage and disease initiate shared pathological glial cell state changes. (2) A second project is testing the hypothesis contusion initiates the expression of transcriptional regulators of the neuronal stress sensor pathway in outer layer neocortical neurons that can be manipulated to improve neuronal resiliency post-trauma. The overall goal of both of these projects is to identify novel therapeutic targets to improve TBI outcomes through a more detailed understanding of spatiotemporal patterns of molecular pathology following a TBI.
The identification of substrates of the E3 ubiquitin ligase UBE3A in human cortical neurons
My laboratory uses human induced pluripotent stem cells (hiPSCs) to generate human cortical neurons for the identification of substrates of the E3 ubiquitin ligase UBE3A. Mutations in UBE3A account for 85-90% of cases of Angelman Syndrome (AS), a complex neurological disorder characterized by developmental delay, intellectual disability, speech impairment, seizures and ataxia. Using unbiased proteomic approaches, we have identified a cohort of putative substrates that function in the endocytic cycling of receptor-channel subunits and in the vesicular packaging, synaptic release and degradation of neurotransmitters.
Representative publications, projects, and/or deployments