Jose F. Abisambra, Ph.D.
Department of Neuroscience
Center for Translational Research in Neurodegenerative Disease
1275 Center Drive, PO Box 100159
Gainesville, FL 32610-0159
|2004||M.S.||University of South Florida, Tampa|
|2010||Ph.D. (Medical Sciences/Molecular Medicine)||University of South Florida, Tampa|
|2010-2012||Postdoctoral Fellowship||University of South Florida, Tampa|
Key Words: Tauopathies, Head Injury, Alzheimer’s disease, Molecular Mechanisms of Learning & Memory, Unfolded Protein Response
My research program investigates fundamental biological processes critical to neuronal function that converge with endoplasmic reticulum (ER) proteins. Our currently supported projects focus on the impact of the Unfolded Protein Response on neurodegenerative processes in Alzheimer’s and related proteinopathies. My work explores protein synthesis (Meier et al., 2016), trafficking (mitochondria, Golgi apparatus, plasma membrane, etc.) (Jinwal et al., 2010), folding (Abisambra et al., 2012; Abisambra et al., 2013a), and clearance (proteasome and autophagy) (Abisambra et al., 2013b) as fundamental processes during brain development, aging, and stress. I further investigate the impact of the ER on calcium homeostasis and lipid/carbohydrate metabolism (Abisambra et al., 2010) in the context of whole neuronal function. Alterations to these processes are linked to the pathogenesis of 25 known neurodegenerative disorders that share a common pathological hallmark: intracellular aggregation of tau. These tauopathies include Alzheimer’s disease (AD), chronic traumatic encephalopathy/traumatic brain injury (CTE/TBI; reviewed in (Abisambra and Scheff, 2014), and fronto-temporal degeneration with tau inclusions (FTD-tau).
While tau is best known as a microtubule stabilizing protein, the emerging role of ER transport along microtubules for highly specialized cells such as neurons suggest that the impact of tau on the ER has major implications for neuronal function. I systematically examined the link between tau and the ER and show that (i) there are hundreds of tau-ER interactions that are still uncharacterized (Meier et al., 2015), (ii) tau impairs ER-associated degradation and causes activation of the unfolded protein response (UPR) (Abisambra et al., 2013b), and (iii) tau abrogates ribosomal function (Meier et al., 2016; Vanderweyde et al., 2016).
The overarching goal of my research program is to investigate the molecular mechanisms linking tau and ER dysfunction with neurodegeneration. This focus creates an opportunity to investigate the integration of essential cellular functions for development, aging, and disease by targeting one organelle. Ultimately, this work can aid in the identification of therapeutic targets for more than 30 million people currently suffering from tauopathies worldwide.