Department of Microbiology and Molecular Genetics
Faculty profile
|
|
Carlos A. Casiano Assistant professor Center for Molecular Biology & Gene Therapy Office of minority student development in the biomedical professions |
- PhD (microbiology): University of California at Davis, 1992
- Postdoctoral fellow (cell biology; immunology): W.M. Keck Autoimmune Disease Center, The Scripps Research Institute (La Jolla)
- Current research interests
- Recent publications
- Teaching
Autoantigen cleavage during apoptotic and non-apoptotic cell death
Apoptosis is a genetically controlled mode of cell death that may be the end result of response to physiologic activators, physical trauma, or environmental toxins and chemicals. Apoptosis is essential for tissue development and remodeling, immune defense, and aging. Apoptosis is also associated with a wide range of human pathological conditions, including systemic autoimmunity, cancer, AIDS, and neurodegenerative disorders. It is now well established that activation of proteases of the caspase family is the central mechanism in the execution of apoptosis. Cell death may also occur by non-apoptotic mechanisms independent of caspase activation, such as the classical necrotic cell death. We have demonstrated that apoptotic and non-apoptotic cell deaths involve the selective proteolytic cleavage of a specific subset of nuclear protein autoantigens. These autoantigens are self-cellular proteins that are targets of autoantibodies in patients with systemic autoimmune diseases such as lupus and scleroderma. Based on the cleavage pattern of autoantigens during apoptotic and non-apoptotic cell death, we proposed the hypothesis that distinct classes of proteases operate in these two modes of cell death. We are interested in defining and differentiating the molecular mechanisms by which specific autoantigens are cleaved during apoptotic and non-apoptotic cell death. The goal is to distinguish in biochemical and molecular terms apoptosis from other cell death pathways. These studies should contribute to our understanding of cell death and provide new reagents that might facilitate the study of cell death in experimental and pathological contexts. Knowledge of how intracellular antigens are structurally altered during cell death may also shed some light into mechanisms by which normal components of cells become immunogenic during certain disease conditions.
Molecular cell biology of cancer-associated autoantigens
Cancer serology is entering a new an exciting era. The observation that human tumors provoke autoantibody responses against self-cellular antigens, including oncoproteins, expressed in the tumors has opened a window of opportunity for the molecular analysis of protein antigens involved in cellular processes linked to malignant transformation such as signal transduction, cell cycle regulation, mitosis, and apoptosis. Knowledge of cancer-associated autoantigens that could potentially stimulate specific anti-tumor immune responses is also essential for exploring and designing novel immunotherapeutic approaches in the treatment of cancer. Using autoantibodies from cancer patients, we identified previously a novel cell cycle-dependent nuclear protein, termed p330d or centromere protein F (CENP-F). This protein appears to play a very important role in mitosis and is currently being used as a marker of cell proliferation. We are now characterizing in our laboratory a putative novel CENP-F-like protein which is the target of an autoantibody response in a patient with lung cancer. Autoantibodies are being used to study the properties and intracelllular localization of this protein during different stages of the cell cycle, and to isolate the corresponding cDNA from an expression library. We have also initiated a program for the systematic screening of sera from patients with prostate cancer treated at LLU Medical Center, with the purpose of identifying autoantibodies to potentially novel cellular autoantigens. The long-term goal of this project is to identify and characterize specific genes and gene products associated with prostate cancer which could provide unique tools for defining signaling pathways involved in prostate malignant transformation, as well as novel targets for therapeutic intervention.
Click on the 
symbol beside the reference to read the corresponding abstract.
Slee, E. A., Harte, M. T., Kluck, R. M., Wolf, B., Casiano, C.A., Newmeyer, D., Wang, H.G., Reed, J. C., Nicholson, D. D., Alnemri, E. S., Green, D. R., and Martin, S. J. (1999). Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases -2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J. Cell Biology 144: 281-292.
Erlanson, M., Casiano, C.A., Tan, E. M., Lindh, J., Roos, G., and Landberg, G. (1999) Immunohistochemical analysis of the proliferation associated nuclear antigen CENP-F in non-Hodgkin's lymphoma. Modern Pathology 12: 69-74.
Casiano, C. A., Ochs, R. L., and Tan, E. M. (1998). Distinct cleavage products of nuclear proteins in apoptosis and necrosis revealed by autoantibody probes. Cell Death and Differentiation 5:183-190.
Miranda, E., Tseng, C., Rashbaum, W., Ochs, R. L., Casiano, C. A., DiDonato, D., Chan, E. K. L., and Buyon, J. (1998). Accessibility of SSA/Ro and SSB/La antigens to maternal autoantibodies in apoptotic human fetal cardiac myocytes. J. Immunology 161: 5061-5069.
Casiano, C. A. and Tan, E.M. (1998). Apoptosis, autoantigens, and autoimmunity. In: The Autoimmune Diseases. Ed. Rose, N. and Mackay, I. Academic Press, San Diego. pp. 193-210.
Casiano, C.A. and Tan, E.M. (1998). Autoantigen cleavage during apoptotic and necrotic cell death. In: Pathogenic and Diagnostic Relevance of Autoantibodies. Ed. Conrad, K., Humbel, R.L., Meurer, M., Shoenfeld, Y., and Tan, E.M. PABST Science Publishers, Lengerich, Germany, pp. 70-84.
Casiano, C.A. and Tan, E.M. (1998). Autoantibodies to centromere protein F. In: Pathogenic and Diagnostic Relevance of Autoantibodies. Ed. Conrad, K., Humbel, R.L., Meurer, M., Shoenfeld, Y., and Tan, E.M. PABST Science Publishers, Lengerich, Germany, pp.395-411.
Pollard, K. M., Lee, D., Casiano, C. A., Johnston, M. M., Bluthner, M., and Tan, E. M. (1997). The autoimmunity-inducing xenobiotic mercury interacts with the autoantigen fibrillarin and modifies its molecular and antigenic properties. J. Immunology 158: 3521-3528.
Ellerby, H. M., Martin, S. J., Ellerby, L. M., Naiem, S. S., Rabizadeh, S., Salvesen, G. S., Casiano, C. A., Cashman, N.R., Green, D. R., and Bredesen, D. L. (1997). Establishment of a cell-free system of neuronal apoptosis: application to mitochondrial-dependent activation. J. Neuroscience 17: 6165-6178.
Rattner, J.B., Rees, J., Whitehead, C.M., Casiano, C. A., Tan, E. M., Humbel, R. L., Conrad, K., and Fritzler, M. J. (1997). High frequency of neoplasia in patients with autoantibodies to centromere protein CENP-F. Clinical Investigative Medicine 20: 308-319.
Talanian, R. V., Yang, X., Turbov, J., Seth, P., Ghayur, T., Casiano, C.A., Orth, K., and Froelich, C.J. (1997). Granule-mediated cell killing: pathways for granzyme B initiated apoptosis. J. Experimental Medicine 186: 1323-1331.
Baez, A., Torres, K., Tan, E. M., Pommier, Y., and Casiano, C. A. (1996). Expression of the proliferation-associated nuclear autoantigens p330d/CENP-F and PCNA during differentiation and drug-induced growth inhibition. Cell Proliferation 29: 183-196.
Landberg, G, Erlanson, M., Roos, G, Tan, E. M., and Casiano, C. A. (1996). Nuclear autoantigen p330d/CENP-F: a marker for cell proliferation in human malignancies. Cytometry 25: 90-98.
Casiano, C. A., Martin, S. J., Green, D., and Tan, E. M. (1996) Selective cleavage of nuclear autoantigens during CD95 (Fas/APO-1)-mediated T cell apoptosis. J. Experimental Medicine 184: 765-770.
Martin, S. J., Amarante-Mendes, G., Tewari, M., Shi, L., Chuang, T.-H., Casiano, C. A., Fitzgerald, P., Tan, E. M., Bokoch, G. M., Dixit, V. M., Greenberg, A. H., and Green, D.R. (1996). The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism. EMBO J. 15: 2407-2416.
Casiano, C. A., and Tan, E. M. (1996). Recent developments in the understanding of antinuclear autoantibodies. International Archives of Allergy and Immunology 111: 307-313.
Casiano, C. A. and Tan, E.M. (1996). Antinuclear autoantibodies: probes for defining proteolytic events associated with apoptosis. Molecular Biology Reports 23: 211-216.
Casiano, C. A., Humbel, R. L., Peebles, C., Covini, G. and Tan, E. M. (1995). Autoimmunity to the cell cycle-dependent centromere protein p330d/CENP-F in disorders associated with cell proliferation. J. Autoimmunity 8: 575-586.
My main teaching interests are in molecular cell biology and immunology, particularly in topics related to molecular mechanisms of cell death, cell cycle regulation, cell division, translational control, ribosome structure and function, biology of the nucleus, immune tolerance, apoptosis in the immune system, and autoimmunity.
School of Medicine - Graduate School - Loma Linda University
[Top]