Jorge Oksenberg, PhD
|School||UCSF School of Medicine|
|Address||675 Nelson Rising Lane|
San Francisco CA 94158
|VA Multiple Sclerosis Center of Excellence ||2009||The John N. Whitaker Memorial Lecture|
|UCSF||2005||G.A. Zimmermann Endowed Chair in Neurology|
Immune-mediated neurological impairment is the outcome of a rather extensive and coordinated series of events that include peripheral lymphocyte activation, disruption of the blood-brain barrier, cellular infiltration into the brain parenchyma, local inflammation and tissue injury. Cytokines, adhesion molecules, growth factors, antibodies, and other molecules (including free radicals, proteases, vasoactive amines, and excitatory neurotransmitters) induce and regulate numerous critical cell functions that perpetuate inflammation, leading to tissue injury, neuro-degeneration, and neurological deficits. The nature and intensity of this response as well as the physiological ability to restore homeostasis are to a large extend conditioned by the unique amino acid sequences that define allelic variants on each of the participating molecules. Genes, either in their germline configuration and/or as part of complex functional networks, play a primary role in determining who is at risk for developing such disorders, how the disease progresses, and how someone responds to therapy.
The principal aim of our laboratory (see link below) is to identify the major genetic factors that predispose to autoimmunity in the central nervous system and modulate disease presentation and progression. The availability of highly sensitive and high-capacity methods for analysis of gene variation and expression combined with the implementation of algorithms that predict behaviors in complex biological circuits provides an outstanding opportunity to facilitate progress in the integration of multiple data sources and functional interpretation of physiological and laboratory results. Our goal is to apply novel molecular, informatic, statistical, and epidemiological approaches to illuminate fully the genetics of autoimmune demyelination. Specifically, our research plan includes:
• Genome wide gene/haplotype mapping for the discovery of MS genes
• Genotype-phenotype correlations in MS
• Gene-environment correlations in MS
• Genomic and clinical study of MS populations at low and intermediate risk
• MS pharmacogenomics
• Gene expression networks in human and experimental neuroinflammation
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