|Department Affiliations||Medicine, Cell Biology and Pathology|
|Rank||Professor, School of Medicine, Vice Dean of Research|
|SOM Address||115 Miller Research Building|
Sarah White 1998 – 2004
Kathryn Roberts 1999 – 2006
Tomeka Suber 2004 – 2008
The immune response to self-antigens in many autoimmune diseases appears to be driven by continued exposure to antigen. However, the mechanisms underlying this ongoing release of autoantigens, and the sites from which this might occur, remain unclear. We have recently observed that autoantigens targeted in systemic autoimmune diseases are unified by their redistribution to surface blebs during apoptosis, and by their susceptibility to structural alterations at this site during unique forms of apoptotic death. We are currently studying the cell biology and biochemistry of autoantigen clustering during cell death induced by different stimuli, including toxins, irradiation and infection, in order to better define the circumstances that might initiate and propagate each of the autoimmune rheumatic diseases.
- Mancini, M., Nicholson, D.M., Roy, S., Thornberry, N., Peterson, E., Casciola-Rosen, L. and Rosen, A., The caspase-3 precursor has a cytosolic and mitochondrial distribution: Implications for apoptotic signaling. J. Cell Biol. 140: 1485-1495, 1998.
- Andrade, F., Roy, S., Nicholson, D.M., Thornberry, N., Rosen, A., and Casciola-Rosen, L., Granzyme B directly and efficiently cleaves several of the downstream substrates of caspases: Implications for CTL-induced apoptosis. Immunity 8: 451-460, 1998.
- Casciola-Rosen, L., Andrade, F., Ulanet, D., Wong, W.B., and Rosen, A., Cleavage by granzyme B is strongly predictive of autoantigen status: Implications for initiation of autoimmunity. J. Exp. Med., 190:815-825, 1999.
- Mancini, M., Machamer, C.E., Roy, S., Nicholson, D.W., Thornberry, N.A., Casciola-Rosen, L.A., and Rosen, A. Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis. J. Cell. Biol. 149: 603-612, 2000.
- Andrade F, Bull HG, Thornberry NA, Ketner GW, Casciola-Rosen LA, Rosen A. Adenovirus L4-100K assembly protein is a granzyme B substrate that potently inhibits granzyme B-mediated cell death. Immunity 14(6): 751-61, 2001. (See comments in J. Cell. Biol. 154: 14, 2001.).
- Andrade F, Casciola-Rosen LA, and Rosen A. A novel domain in adenovirus L4-100K is required for stable binding and efficient inhibition of human granzyme B: Possible interaction with a species-specific exosite. Mol. Cell. Biol. 23: 6315-6326, 2003.
- Ulanet DB, Torbenson M, Dang CV, Casciola-Rosen L, and Rosen A. Unique conformation of cancer autoantigen B23 in hepatoma: A mechanism for specificity in the autoimmune respone. Proc. Natl. Acad. Sci. 100: 12361-12366, 2003.