Please Enter a Search Term
 
"Building a Healthy Tomorrow"  TM
AdmissionsCommunicationsDivision/DisciplineEducationFaculty/StaffLeadershipResearchStudents
Division of BioMedical Sciences


Our People - Faculty Websites - KarenMearow_Research Interests

Research Area:

My main interests are in how neurons respond to stress and injury, using mature peripheral sensory neurons and neonatal CNS neurons or cell lines as part of our research models.

Current work:

Alzheimer disease models:  I am interested in understanding how amyloid beta (Aβ) affects neurons from a cell biology perspective using in vitro models of cell lines or primary CNS neurons (hippocampal, cortical).  We have investigated how the small heat shock protein can protect neurons from Aβ exposure (King et al 2009).  HspB1 also appears to be able to modify the processing of the amyloid precursor protein and alter the release of the more toxic Aβ 1-42 peptide (Conway et al 2014).  We have also addressed the role of astrocytes in amyloid toxicity, showing that exposure of astrocytes to Aβ results in a release of HspB1/Hsp27; this extracellular HspB1 directly interacts with the amyloid peptide and may play a role in sequestering excess amyloid and preventing toxic effects on neurons (Nafar et al 2016).

Currently we are examining whether coconut oil (highly enriched in medium chain fatty acids, as well as diverse polyphenolic compounds) had any effect on neurons, and whether it can protect against Aβ toxicity.  Anecdotal accounts have suggested that ingestion of coconut oil may be able to ameliorate some of the effects of Alzheimer’s disease, although the scientific evidence for this is still somewhat controversial. Our results suggest that coconut oil does rescue neurons from Aβ toxicity, and one way this might occur is via upregulation of cell survival signaling pathways (such as activation of Akt) (Nafar et al 2014; Nafar et al 2016, under review).

Autophagy has been implicated as a potential modulating factor in the response of cells to stressful stimuli, particularly in the context of neurodegenerative diseases.  Constitutive autophagy is thought to aid cells in the normal recycling of cellular organelles or proteins, to prevent buildup of potentially toxic metabolites or protein aggregates. It can promote cellular survival during starvation by maintaining cellular energy levels though recycling of redundant proteins and organelles.  Adult sensory neurons tend to be relatively resistant to stresses that result in the death of other neurons (such as thermal or chemical stresses) and autophagy is thought to be important in this characteristic.  Our recent study (Clarke and Mearow, 2016) showed that autophagy is a constitutive process in DRG neurons and contributes to neuronal survival and neurite growth and regeneration.  There is still much to be learned about the signaling pathways that regulate this process in neurons, particularly under stressed conditions (such as injury or amyloid exposure).

Previous work:

We have previously studied the small heat shock protein, and investigated its role in axonal growth and survival showing that post-translational modifications in the protein are important to its interactions with cytoskeletal components (especially actin) and that these are key for neurite growth and cell motility (Mearow and Williams, 2011; Clarke and Mearow, 2013).

Our earlier studies focused on mechanisms that contributed to the survival and neurite regeneration of mature sensory neurons.  Our results provided evidence for a key contribution of the extracellular matrix in promoting the regeneration of specific populations of sensory neurons in the dorsal root ganglion (Tucker and Mearow, 2008; Fudge and Mearow, 2013). 
 
 
Copyright © 2017 Memorial University of Newfoundland.   Newfoundland and Labrador, Canada.