Lab Research Focus
My laboratory in the Division of Clinical Immunology and Rheumatology relies heavily on the use of mutant and transgenic strains of autoimmune mice, particularly Fas mutant lpr/lpr and Fas ligand mutant gld/gld mice.
My research has focused on understanding the cellular and molecular basis of autoimmune diseases. To accomplish this we have used several strains of mice with an emphasis on the lpr (lymphoproliferative) strain. The lpr gene was identified in 1992 as a mutant form of the Fas apoptosis gene. Therefore, my laboratory has focused on Fas, Fas ligand and the Fas apoptosis signaling pathways. Other receptors and ligands homologous to Fas and containing the Fas death domain (including TNF receptor type I and TNF receptor pathways) are also being investigated.
A second focus for my laboratory is investigation of Longevity Assurance Genes (LAG). A defect in apoptosis with aging has been described by myself and other investigators, and therefore apoptosis molecules such as Fas have been proposed as LAGs and have been investigated with the focus on their effects on the immune system. More recently other aging genes have been identified including a Werner's Syndrome gene, and this has been cloned in my laboratory and is being used to produce transgenic and knockout mice. A second gene, the Age-1 gene in yeast, is also being investigated.
A third focus in my laboratory is the use of gene therapy to correct autoimmune disease. This involves the use of adenovirus vectors with different products related to Fas ligand and soluble TNF-RI. These products are being used to down-modulate the immune response and create immune-privileged sites. Also, targeted forms of the vector have been produced by modifying the fiber/knob protein of this vector which is being used to allow site-specific expression of the vector.
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