University of Texas Graduate School of Biomedical Sciences, Houston, Texas
Gladstone Institute of Neurological Disease and University of California San Francisco, San Francisco, California
Assistant Professor, 2010
Research and Clinical Interests
The focus of my research is to understand the cellular and network mechanisms underlying cognitive impairments in Alzheimer's disease (AD), and to identify therapeutic entry points for the treatment of this devastating disease. The amyloid precursor protein (APP) and the amyloid-β (Aβ) peptides derived from it play a central role in AD, although the precise mechanisms by which they impair neuronal function and lead to cognitive deficits remain to be fully defined. Transgenic mouse models of AD produce high levels of Aβ and develop neuropathology and memory deficits similar to those observed in patients with AD, and are thus extremely useful for interrogating the role of Aβ in memory impairments.
Notably, Aβ disrupts synaptic transmission and impairs learning and memory before frank neurodegeneration is observed. This suggests that elucidating the mechanisms by which Aβ perturbs neuronal function will pave the way for development of treatments that improve cognitive function and delay or prevent the progression of the disease.
To this end, we use a multi-disciplinary approach that combines biochemistry, immunohistochemistry, in vivo physiology, and behavioral paradigms to link cellular alterations to memory deficits in transgenic mouse models of AD. We use video-recorded EEG measurements to characterize patterns of (aberrant) brain activity in individual mice and correlate this activity with performance in various behavioral paradigms designed to test different aspects of memory and cognitive function. Finally, we use biochemical, molecular, and immunohistochemical techniques to examine the links between alterations in particular proteins or pathways and dysfunction of cognitive processes on a mouse-by-mouse basis. This integrated approach allows us to investigate the molecular basis of memory impairments observed in AD and to identify therapeutic entry points for the treatment of this neurodegenerative disease.