Cytokine Receptors, Drug Resistance, Oxidative Stress and Cell Death

Over the years my lab studied the mode of action of various cytokines, focusing on identification of cytokine receptors and binding proteins. We Isolated and characterized the human interferon alpha, demonstrating that it consists of multiple species encoded by several genes. Together with Dr. Daniela Novick and others, we cloned the ligand-binding subunit of the Type I interferon receptor (IFNAR2) and IL-18 binding protein, a unique cytokine inhibitor.  We have isolated and identified many soluble receptor forms, including those of IL-6, IFN-gamma, TNF, and LDL. In later years we discovered that the LDL receptor and its other family members are the entry ports of vesicular stomatitis virus, an observation highly relevant to gene therapy. In parallel, we studied two major topics: 1. The role of the transcription factor C/EBPβ in cell survival and death, with a particular emphasis on tumor drug resistance. 2. The role of solid tissue-generated leukotrienes in formation of reactive oxygen species, oxidatve DNA damage and subsequent cell death. Our studies led to the development of three approved drugs and a fourth one is currently in advanced clinical trials.