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About Us : Faculty : Bonavida

Benjamin Bonavida, Ph.D.
Professor, Department of Microbiology and Immunology, UCLA School of Medicine
Associate Member, Cousins Center for Psychoneuroimmunology, UCLA Neuropsychiatric Institute

 Research Interests

Our research interests have focused in areas of both cellular and molecular immunology as they relate to infection and cancer. During the last several years the laboratory has focused on two areas of research investigations: (1) The molecular mechanism by which rituximab (chimeric anti-CD20 monoclonal antibody), approved by the FDA in 1999 for the treatment of non-Hodgkin’s B lymphoma, mediates its effects when used alone or in combination with chemotherapy. (2) At present, immunotherapy is being considered as a novel therapeutic approach in the treatment of cancer patients who do not respond to conventional therapies. We have been interested in investigating the molecular mechanism by which cancer patients develop resistance to immunotherapy.

Current Research Projects

1. Our studies with rituximab have revealed that it can trigger the lymphoma cells via the CD20 receptor and modify several intracellular constitutive survival pathways that result in the downregulation selectively of anti-apoptotic gene products. These studies were the first to demonstrate that rituximab sensitizes tumor cells to chemotherapy-induced apoptosis. These studies also examine the underlying mechanisms by which rituximab modifies these intracellular signaling pathways and regulate survival or cell death by apoptosis. In addition, research underway examines the mechanism of rituximab resistance that is observed in vivo. In this area we have generated rituximab-resistant clones for cellular, molecular and genetic analysis to identify gene products that regulate resistance. In addition, we have been examining both in vitro and in vivo, the effect of rituximab on multiple myeloma, which comprises a subset of CD20 + stem cells.

2. Our studies on the immune-resistance of cancer cells stem from our findings that tumor cells that become resistant to drugs also develop cross-resistance to immune-mediated cytotoxicity. Several studies have examined the underlying mechanisms of immune-resistance and identified several gene products involved. In particular, we have identified the role of the transcription repressor YY1 in the regulation of immune-resistance. The transcription and post-transcription regulation of YY1 and its inhibition in the reversal of resistance are being examined both in vitro and in vivo.

Recent Publications (from July 01, 2003 to June 30, 2004)

Whiting D, Hsieh G, Yun JJ, Banerji A, Yao W, Fishbein MC, Belperio J, Strieter

RM, Bonavida B, Ardehali A. Chemokine monokine induced by IFN-gamma/CXC chemokine ligand 9 stimulates T lymphocyte proliferation and effector cytokine production. J Immunol, 172: 7417-24, 2004.

Vega M, Huerta S, Garban H, Jazirehi A, Emmanouilides C, and Bonavida B. Rituximab inhibits p38 MAPK activity in 2F7 B NHL and decreases IL-10 transcription: Pivotal role of p38 MAPK in drug resistance. Oncogene, 23: 3530-3540, 2004.

Huerta S, Vega M, Jazirehi A, Garban H, Hongo F, Cheng G, and Bonavida

B. Nitric oxide sensitizes prostate carcinoma cell lines to TRAIL-mediated apoptosis via inactivation of NF-kB and inhibition of Bcl-xL expression. Oncogene, 23: 4993-5003, 2004.

Jazirehi, A. and Bonavida, B. Resveratrol modifies the expression of apoptotic regulatory proteins and sensitizes Non-Hodgkin’s Lymphoma and multiple myeloma cell lines to paclitaxel-induced apoptosis. Molec Canc Therap., 3: 71-84, 2004.

Jazirehi, A.R., Gan, X-H., De Vos, S., Emmanouilides, C., and Bonavida, B. Rituximab (anti-CD20) Selectively Down-Regulates Bcl- xL and Up-Regulates Apaf-1 in Non-Hodgkin’s Lymphoma (NHL) B-Cells: Complementation with Paclitaxel Results in Synergy in Apoptosis. Molec Canc Therap., 2:1183-1193, 2003.

Fischbein, M.P., Yun, J., Laks, H., Irie, Y., Oslund-Pinderski, L., Fishbein, M., Bonavida, B. and Ardehali, A. Regulated IL-10 Expression prevents chronic rejection of transplanted hearts. J. of Thoracic and Cardiovascular Surgery, 261(1):216-223, 2003.

Bonavida, Benjamin
Microbiology, Immunology & Molecular Genetics
A2-060 CHS
43-233 CHS
mail code: 174718
phone: 310-825-2233
email: [email protected]

 

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