HIV-associated cognitive disorders remain prevalent, even among HIV positive individuals who receive highly active anti-retroviral treatments. There is a wealth of HIV-related neuroscience research at Johns Hopkins University (JHU), especially focused on oxidative stress as a critical pathogenic mechanism for neurological damage. Despite this rich environment, no definitive therapeutics for HIV-associated cognitive disorders have yet been developed. There is also an unfilled need to develop surrogate markers and more robust and simpler screening instruments for neurological diseases, which could eventually be used in resource-limited areas or by non-neurologists. Potential collaborations at Johns Hopkins are currently limited by the lack of a central organizing structure for this type of research and resources to facilitate cross-disciplinary and translational research. The JHU NIMH Center will address these needs to provide a resource to catalyze interdisciplinary research in HIV neuroscience. The goals of the JHU NIMH Center are to: 1. To facilitate collaborative research in HIV-related neuroscience with the goal of developing a definitive therapy for HIV-associated cognitive disorders based on targeting oxidative stress pathways. 2. To increase resources for HIV-related neuroscience research at JHU and to enhance the productivity of HIV-related neuroscience research locally, nationally and internationally. 3. To encourage high-risk, innovative developmental research in Neuro-AIDS, especially of a cross disciplinary nature. 4. To provide resources to encourage new investigators locally, nationally, and internationally to enter the field of HIV Neuro-AIDS research by providing educational and skill-developing resources for investigators to improve their expertise in detecting and treating HIV-related neurological complications. 5. To use focused throughput screening, using in vitro models to identify novel compounds useful for treatment of HIV-associated cognitive dysfunction with the over-arching theme of oxidative stress. 6. To identify and validate surrogate biomarkers based on proteomics and lipidomics[PSB1]. Administrative Core DESCRIPTION (provided by applicant): The overarching theme of the Center is the development of novel therapeutics for HIV-associated cognitive disorders and dementia. We have identified this as a high priority on the basis of our institutional strengths and continuing importance in clinical care. There is already a wealth of investigator-initiated HIV neuroscience research at Johns Hopkins University (JHU), especially focused on pathogenesis, as well as significant expertise in clinical trial design, and international work. Despite this rich environment, novel therapeutics for HIV-associated cognitive disorders have not entered clinical practice. Within the JHU HIV Neuroscience community, potential collaborations are limited by the lack of a central organizing structure, and specifically a facility to link different types of research, and to facilitate cross-disciplinary research. This Center will address these deficiencies. To achieve this goal, we propose to use the Center to bring together several HIV and simian immunodeficiency virus (SIV) neuroscience researchers at JHU, to work together on these goals. One of the strengths of the Center is that it builds on, and amplifies, the existing work in HIV-associated cognitive disorders and dementia (HIV-D), cognitive testing, clinical trials, therapeutic development and animal models of SIV encephalitis. All of this work is well established, but has not, to date, been fully integrated together. Newer areas of research, in the development of surrogate markers, in developing medication adherence markers, and in international work, will be added to bolster these aspects of interactive research. [PSB1]lipidomics?
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