Ebrahim Zandi Assistant Professor Molecular Microbiology & Immunology USC / Norris Comprehensive Cancer Center Keck School of Medicine

Research Topics: Signal Transduction, Cancer Cell Biology

Research Description

Currently my laboratory works on two research projects: One is to decipher the basic molecular mechanisms of signal transduction by IkB kinase complex (IKK), and the other is to delineate the roles of IkB kinase complexes in the carcinogenesis and the development of drug resistance in cancer therapy.

IKK is a multi-subunit protein kinase complex, which receives and integrates the signals from about 200 stimuli such as bacterial and viral infection, pro-inflammatory cytokines, growth factors, therapeutic drugs, and environmental stressors (UV, X rays and hazardous chemicals). IKK then activates Nuclear Factor kappa B (NF-kB) transcription factors, and other yet to be determined proteins. In turn, NF-kBs, depending on the nature of the signal, induce changes in the pattern of gene expression in the nucleus. These in turn regulate cell proliferation, death, differentiation, and cell to cell communications. Regulating these cellular processes with specificity are essential for the formation and development of a number of organs including the proper development and function of the immune system. Very importantly, immune responses to injury and infections are orchestrated by NF-kBs through IKK. How IKK receives and integrates signals from 200 different stimuli are not known.

We are using biochemical reconstitution assays, molecular and cell biology methods to understand the molecular regulation of IKK and its regulatory mechanisms. We have also reconstituted IKK in the heterologous yeast for mechanistic and structure/function analyses. Others and we have recently discovered that IKK complex is involved in the malignant transformation and development of drug resistance in cancer. We have established experimental systems to determine the mechanism of action of IKK in these processes. Our systems include animal models for cancer, cell culture for drug resistance assays, and analysis of changes in the pattern of gene expression using gene ship micro-array technology.

Selected Publications

Fukaya Y, Shimada H, Wang LC, Zandi E, Declerck YA. - Identification of Gal-3 binding protein as a factor secreted by tumor cells that stimulates interleukin-6 expression in the bone marrow stroma. - J Biol Chem [ 2008 ] May 1; . PubMed

Wang LC, Okitsu CY, Kochounian H, Rodriguez A, Hsieh CL, Zandi E. - A simple and inexpensive on-column frit fabrication method for fused-silica capillaries for increased capacity and versatility in LC-MS/MS applications. - Proteomics [ 2008 ] Apr 2;8(9):1758-1761 . PubMed

Peng Z, Peng L, Fan Y, Zandi E, Shertzer HG, Xia Y. - A critical role for IkappaB kinase beta in metallothionein-1 expression and protection against arsenic toxicity. - J Biol Chem [ 2007 ] Jul 20;282(29):21487-96 . PubMed

Niewolik D, Pannicke U, Lu H, Ma Y, Wang LC, Kulesza P, Zandi E, Lieber MR, Schwarz K. - DNA-PKcs dependence of Artemis endonucleolytic activity, differences between hairpins and 5' or 3' overhangs. - J Biol Chem [ 2006 ] Nov 10;281(45):33900-9 . PubMed

Higashimoto T, Panopoulos A, Hsieh CL, Zandi E. - TNFalpha induces chromosomal abnormalities independent of ROS through IKK, JNK, p38 and caspase pathways. - Cytokine [ 2006 ] Apr;34(1-2):39-50 . PubMed

Schomer-Miller B, Higashimoto T, Lee YK, Zandi E. - Regulation of IkappaB kinase (IKK) complex by IKKgamma-dependent phosphorylation of the T-loop and C terminus of IKKbeta. - J Biol Chem [ 2006 ] Jun 2;281(22):15268-76 . PubMed

Tsur D, Tanner S, Zandi E, Bafna V, Pevzner PA. - Identification of post-translational modifications via blind search of mass-spectra. - Proc IEEE Comput Syst Bioinform Conf [ 2005 ] :157-66 . PubMed

Tsur D, Tanner S, Zandi E, Bafna V, Pevzner PA. - Identification of post-translational modifications by blind search of mass spectra. - Nat Biotechnol [ 2005 ] Dec;23(12):1562-7 . PubMed

Tanner S, Shu H, Frank A, Wang LC, Zandi E, Mumby M, Pevzner PA, Bafna V. - InsPecT: identification of posttranslationally modified peptides from tandem mass spectra. - Anal Chem [ 2005 ] Jul 15;77(14):4626-39 . PubMed

Wang LC, Okitsu CY, Zandi E. - Tumor necrosis factor alpha-dependent drug resistance to purine and pyrimidine analogues in human colon tumor cells mediated through IKK. - J Biol Chem [ 2005 ] Mar 4;280(9):7634-44 . PubMed