The overarching goal of our lab is to investigate the mechanisms by which tau mediates neuronal dysfunction. This is a common phenomenon in more than 25 known neurodegenerative disorders termed tauopathies. The most common tauopathies are Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), Down’s Syndrome (DS), chronic traumatic encephalopathy (CTE), and approximately 40% of cases of fronto-temporal dementia (FTD).
Our current focus is to determine the impact of pathological tau on the endoplasmic reticulum (ER). We have identified that tau impairs ER functions by binding differentially to ER proteins in diseased brains. Affected functions include impairment of ER-associated degradation, chronic activation of the unfolded protein response, and diminished ribosomal function. We are currently characterizing tau-ER interactions using in vitro and in vivo models as well as human brains from AD, PSP, DS, CTE, and FTD cases. Our goal is to determine the normal and abnormal characteristics of the tau-ER relationship, which will lead to identification of novel therapeutic targets.
We are experts in investigating the molecular mechanisms of neuronal damage. In March of 2013, we established a strong research program supported by the University of Kentucky (UK) Alzheimer’s Disease Center (ADC), the Department of Defense, NIH (NINDS, NIA, NIMH, NIGMS, NCATS), GlaxoSmithKline, and the Alzheimer’s Association. The unique resources available to our lab, such as small animal MR imaging, ADC cohort biospecimens, and the COBRE Viral Production Core (developing CRISPR/Cas9 technology in hiPSCs), have strengthened the impact of our work and brought us closer to understanding the mechanisms of tau-mediated neurotoxic events stemming from the ER.