Dysferlin in Apoptosis

Christina Jamieson, PhD

University of California at Los Angeles (Los Angeles CA)

Dr. Jamieson is an Assistant Professor of Urology at the University of California at Los Angeles David Geffen School of Medicine (Los Angeles, CA).

Past Projects

Objective: 
Identify the role of dysferlin in apoptosis in lymphocyte and muscle cell development

Apoptosis is the process of programmed cell death in which the cell is dismantled and cleared without damage to the surrounding tissue. It is well established that defects in T cell apoptosis can lead to immune defects such as autoimmune diseases; however, the role of apoptosis in muscle development and homeostasis is less understood. Using genome-wide DNA microarray gene expression profiling, we found that glucocorticoids activated expression of dysferlin in CD4+ T lymphocytes during apoptosis. In the absence of dysferlin, apoptosis signals may trigger a defective process that instead results in necrosis, that is, uncontrolled cell rupture and release of toxic cell contents causing damage and inflammation in the surrounding tissue. We are using mouse muscle, mesenchymal stem cells and T cell development models as well as human muscle and lymphoid cells to elucidate the molecular mechanism of dysferlin function in apoptosis and the potential defect in its absence. We will determine if this is a specific response to glucocorticoids or part of a general pathway for apoptosis. Our aim is to identify novel targets for molecularly targeted therapy that restore the apoptosis pathway in dysferlin-deficient cells.