Primary Appointment

One of the major concerns in cancer therapeutics is the development of multidrug-resistance (MDR) phenotype in metastatic diseases. I am interested in the mechanisms and reversal of MDR phenotypes in experimental cancer models. The outcome of my studies indicate that MDR can be influenced by the microenvironment and/or factors of specific host organs. The MDR product P-gp may be regulated by cytokines such as TGF-alpha, TGF-beta, TNF-alpha and interferons. My research include the reversal of cancer resistance to anticancer drugs by pharmacologic modifiers, and studying the effects of microenvironment, and cytokines on MDR and tumor angiogenesis.

I participate in studies on the effects of selective tyrosine kinase inhibitors such as STI571 (imatinib mesylate, Gleevec; anti-PDGFR phosphorylation) and AEE788 (anti-EGFR and anti-VEGFR phosphorylation) in preclinical pharmacology and experiemntal orthotopic tumor models. The purpose is to address their efficacy and mode of mechanisms pertinent to the survival pathways of tumor cells and specific tumor-associated vasculartures, and the drug resistant phenotypes of cancer cells. Studies from our orthotopic animal modeles (prostate, ovarian, lung, head and neck cancers) showed that interference with these signal transduction pathways often affected the tumor-associated vasculature to produce an antitumor effect.

I also use relevant experimental therapeutic models to study the biology of brain metastasis; with emphasis on the influence of neuro-microenvironment, e.g., astrocyte-mediated protection of cancer cells and microglia-mediated selective cytotoxicity against cancer cells.

Last updated: 10/28/2009