Research: Our research group is interested in studying the genetic basis for thoracic and head and neck cancers. One goal of our group is to identify and collects samples from young patients who present with these tumors. We recently identified the genetic basis for pulmonary mucoepidermoid carcinoma by isolating and cloning the chromosomal breakpoint of a t(11;19) translocation detected in three of our patients at the National Naval Medical Center. We have cloned the two novel genes that form a mutant gene fusion protein in these tumors and have shown that this Mect1-Maml2 chimeric protein underlies the most common type of malignant salivary gland tumor in humans. We also showed that the fusion protein is oncogenic for primary epithelial cells and that RNAi inhibition of Mect1-Maml2 induces rapid cell death of mucoepidermoid cancer cell line, but show no effect on other primary or tumor cells that do not carry the Mect1-Maml2 rearrangement. Recent data shows that the Maml2 component is part of an essential co-activator for the NOTCH signaling pathway and the Mect1 component is part of an essential co-activator for cyclic-AMP/CREB signaling. Future work will help define a mouse model and candidate pre-clinical and clinical studies. In addition, we have studied the role of the RB tumor suppressor pathway in human cancer and have demonstrated that the RB/p16 tumor suppressor pathway is inactivated in 100% of small cell lung cancer (SCLC) and non-SCLC. We are currently interested in examining the interrelationships between RB/p16 and the cyclin d/ras pathways in neuroendocrine tumorigenesis by defining abnormalities in these pathways within the immortalized tumor lines developed at the National Naval Medical Center. We are also interested in conducting a pilot study at the naval Hospital to detect somatic alterations within thoracic mesothelioma samples using complementary high-resolution genomic methodologies.
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