Signaling - Trafficking - Aggregation - Neurodegeneration - Learning & Memory


The primary emphasis of my research group is centered on unraveling neurotrophin signal transduction. We are working towards elucidating the mechanism whereby nerve growth factor (NGF) binds p75 and TrkA receptors to activate the transcription factor nuclear factor kappa B. During the course of our studies we have discovered a unique bridge molecule, p62, which coordinates p75/TrkA signaling. Sequestosome/p62, binds lysine 63 polyubiquitinated proteins and impairment in the trafficking pathway directed by p62 can lead to inhibition of TrkA signaling along with accumulation of K63 polyubiquitinated substrates within cellular inclusion bodies. The proteins localized within these inclusions are similar to those localized to aggregates obtained from brain of individuals suffering from Alzheimer’s disease. Employing a knockout mouse for p62 we are hoping to unravel the interconnections between signaling-aggregate formation-synaptic plasticity and behavior. Long term we are interested in identifying novel targets for the development of therapeutics to treat neurodegeneration. Studies in my laboratory utilize a multidisciplinary approach that include: tissue culture, biochemical assays, proteomics, antibody arrays, microarrays, mass spec, electrophoresis, knock out mice, histochemistry, confocal microscopy, transfection, site-directed mutagenesis, bioinformatics and structural biology. Individuals in the laboratory become an integral and independent member of our team and gain hands-on expertise in experimental design, reading of the scientific literature, laboratory techniques, data collection, data presentation, meeting attendance, as well as, publishing. The laboratory has been funded primarily from the NIH for 15 years and Dr.Wooten served as a member of the Drug Screening Consortium directed by the NINDS. Members of the laboratory have been awarded fellowship support from the Department of Energy, American Heart Association and the Howard Hughes Foundation.