Texas Repository for AIDS Neuropathogenesis Research

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DESCRIPTION (provided by applicant): This application for renewal of the Texas NeuroAIDS Research Center (TNRC; "Texas") responds to RFAMH-08-021. Texas is part of the National NeuroAIDS Tissue Consortium (NNTC) which includes 3 additional sites at the Mt. Sinai School of Medicine, UCLA, and the UC San Diego. Part A of the application is identical for all 4 sites and contains overall aims, operations and shared agendas of the NNTC. Part B is the Site-specific application. Texas will address the Part A scientific agenda as follows: 1) In host genetics we primed the unit by testing and constructing a pathologically based DNA bank of NNTC materials. Collaboration is underway using 556 DNA isolates, and serves as a template for utilization by the NNTC. 2) For neurovirology aims the Texas unit is primed to collaborate by developing a durable assay of HIV load in autopsy brain specimens that will be used in the NNTC Part A agenda. 3) In the area of biomarkers, Texas will play a prime role in collaborating with the NNTC's need to developing markers of peripheral neuropathy, using results from our unique proteomic analysis of NNTC sensory ganglia. 4) Texas is primed to collaborate in HIV neuropsychiatric comorbidity by expanding upon new insights obtained in an NNTC driven R01 project to elucidate the role of altered dopamine receptors in cocaine use and depression; we will contribute new data and technology to the Part A agenda. 5) Texas is primed to interact in the area of aging comorbidity; techniques were scouted in an NNTC-driven R01 to determine how interferon responses drive protein misfolding and pathological accumulation of brain protein including amyloid. We plan to increase the pool of elderly people in Texas cohort to increase the feasibility of performing translational studies in elderly people with HIV/AIDS. 6) Texas is primed to address discovery of neurochemical breakthroughs because we played a key role in the NNTC gene array project. We will pursue interferon response proteins as biomarkers, which is a key focus of the Part A agenda. 7) Texas is primed to play a part in the drive to delineate the individual effects of gray and white matter pathology on specific neurocognitive domains; we contributed a useful biomarker in white matter to the Part A agenda, which opens the door to further development. 8) Texas will continue to lead the neuropathology quality assurance program of the NNTC in the Part A agenda. These niches conform to certain strengths of Texas that, if exploited fully, can provide breadth and reach to the NNTC agenda. Texas stands ready again to work together to insure that the NNTC remains a vital and lasting national resource in the future. Part A: