Pathogenetics staff

Research

The aim of the Pathogenetics Unit is to investigate genetic alterations underlying tumor development and progression. Emphasis is placed on the study of human cancer as it occurs in vivo, and on the integration of basic research, clinical information, and developing technologies. The three areas of focus are: (1) technology/methodology development; (2) prostate cancer; and (3) multiple endocrine neoplasia type I (MEN1). To overcome the problems of tissue heterogeneity, the Pathogenetics Unit codeveloped both laser capture microdissection (LCM) to increase the speed and efficiency of tissue microdissection, and layered expression scanning (LES) to facilitate high-throughput molecular profiling of tissue samples. In parallel, several associated methodologies have been developed to improve the accuracy and sensitivity of molecular analysis of clinical specimens. In the study of prostate cancer, the laboratory is taking a three-dimensional analytical approach to examine the entire prostate gland and the physical and molecular relationship of tumor progression. An important future goal is to integrate genomic and protein data with gene expression data sets such that a comprehensive analysis of the status of genes and gene products will be possible. Much of the current work is being performed as a part of the NCI's Cancer Genome Anatomy Project (CGAP). MEN1 is an inherited syndrome characterized by development of multiple neuroendocrine (NE) tumors in affected individuals. The responsible gene was recently discovered by the NIH MEN1 working group, including the Pathogenetics Unit and groups from the National Human Genome Research Institute, the National Center for Biotechnology Information, and the National Institute of Diabetes and Digestive and Kidney Diseases. Germline mutations in the MEN1 gene result in formation of NE tumors in a predictable manner and include tumors from multiple organs. Thus, studies of the gene and gene product (menin) are a unique and exciting opportunity to gain new insights into fundamental events and principles of tumor formation. Specific projects of the Pathogenetics Unit include characterization of MEN1 gene mutations in neuroendocrine lung tumors, and immunohistochemical evaluation of menin in human tissues.