Mechanisms of Neuropathogenesis Program
Overview
This program supports basic and clinical research to determine cellular and molecular mechanisms of neuropathogenesis caused by HIV and associated opportunistic and co-infections in both the developed and developing world. HIV neuropathogenesis research that utilizes state-of-the art approaches derived from the fields of molecular biology, virology, neurology, immunology, neuropsychology and epidemiology are encouraged.
Areas of Emphasis
- Evaluate the mechanisms of entry and replication of cell-associated and cell-free virus into the CNS compartment through the blood-brain barrier, focusing on the mediating effects of chemokine receptors, adhesion molecules and syndecans.
- Study the interactions of viral proteins (Tat, Vpr, Nef, gp 120) with CNS derived cells, including studies of the impact of viral proteins on damage to blood-brain barrier, induction of release of mediators (chemokines, cytokines, excitotoxins) and activation of apoptotic pathways, particularly in neuronal cells.
- Assess the impact of host derived mediators and associated receptors (cytokines, chemokines, chemokine receptors, matrix metalloproteinases, thrombin, proteinase-activated receptors) on HIV-neuropathogenesis.
- Identify the signaling pathways involved in neuronal damage and apoptosis or release of inflammatory mediators following interaction of virus or viral proteins with CNS-derived cells.
- Identify the molecular markers associated with HIV-induced nervous system disease, using microarrays, proteomics and neuroimaging approaches to define markers that are predictive of HAD and are associated with disease progression and response to therapy.
- Assess the incidence and prevalence of neurologic complications caused by HIV and associated opportunistic infections and co-infections in resource limited settings, including mechanisms of neuropathogenesis induced by distinct clades of HIV and unique opportunistic pathogens and co-infections in resource limited settings.
Contact
Jeymohan Joseph, Ph.D.
Program Chief
6001 Executive Boulevard, Room 6202, MSC 9619
301-443-3012, jjeymoha@mail.gov
