Areas of Interest - Basic Research

Lung Cancer

Dubinett: Our research focuses on the mechanisms of tumor-mediated immune suppression in lung cancer. The delineation of specific immune inhibitory networks in lung cancer has also led to the development of preclinical models and clinical trials that utilize this new information in translational research in genetic immunotherapy. We have found that non-small cell lung cancer cells (NSCLC) express type 2 cytokines and potently induce lymphocyte and macrophage production of the immunosuppressive cytokine, IL-10. This suppressive network is dependent upon both expression of cyclooxygenase 2 (COX-2) and high-level production of PGE2 by NSCLC cells. We are studying the effect of genetic modulation of COX-2 in lung cancer. We find that high level COX-2 expression is responsible for lung tumor invasiveness and resistance to apoptosis as well as degradation of cell-mediated immune responses. Additional research focuses on restoration of antitumor immunity by introduction of genetically modified antigen presenting (dendritic) cells at the lung cancer site.

Sarafian: Current projects with Dr. Michael Roth and Dr. Don Tashkin focus on toxic mechanisms of marijauana smoke in the lung which may contribute to pulmonary disease, especially lung cancer. These mechanisms include high levels of oxidative stress and impairment of apoptosis pathways. Most studies utilize in vitro experimental models and compare marijuana and tobacco smoke. Studies are also performed on lung cells obtained from volunteer subjects by bronchiolar lavage.

Collaborative studies with Dr. Wayne Grody focuses on DNA damage caused by tobacco and marijuana smoke.

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