Cel
Glucocorticoid (GC) -induced apoptosis, although frequently not recognized, is a poorly understood phenomenon of major clinical significance: First, it is a central component in the treatment of lymphoid malignancies. Second, through its postulated effect upon immune repertoire generation, it might contribute to the pathogenesis of autoimmune diseases. We propose to investigate
(a) the molecular basis of GC-induced apoptosis,
(b ) mechanisms of the therapeutically important GC resistance, and
( c ) the role of these phenomena in autoimmune disease pathogenesis, thereby providing the basis for improved therapy of lymphoid malignancies and perhaps autoimmune disorders. The research will be performed by combining the expertise of clinical and basic scientists from 5 internationally renowned groups that will exploit functional genomics and other molecular techniques to analyse normal and malignant lymphocytes from afflicted patients, and from genetically modified and spontaneously autoimmune mice.