Mark A. Watson, M.D., Ph.D.

DEPARTMENT OF Pathology & Immunology
Keywords: breast cancer, cancer, functional genomics, gene expression, pathogenesis

We are studying secretoglobins, a cluster of six homologous genes located on human chromosome 11q12, as they relate to human breast cancer. Each secretoglobin gene encodes a secreted polypeptide that forms a covalently linked, combinatorial multimer with other secretoglobins. Experimentally, these quaternary structures bind steroid-related ligands, modulate inflammatory processes, and affect the invasive behavior of tumor cells. The expression of one secretoglobin, which we have named mammaglobin, is generally restricted to the mammary epithelium and is elevated in almost 80 percent of human breast tumors. Cell culture and animal models are used to understand the functional role of mammaglobin and related secretoglobin proteins in breast cancer progression, while primary human tumors and high density oligonucleotide microarrays ('GeneChips') are utilized to elucidate the mechanisms controlling the tumor-specific expression patterns of these genes. In addition to providing new insights into breast development and tumorigenesis, we hope that results from these studies will identify a new therapeutic target for breast cancer.

In collaboration with other clinical and basic science investigators, we also use microarrays to monitor gene expression in other human tumors (brain, lung, pancreas, and breast). Using a technique called Laser Capture Microdissection, we are isolating subpopulations of cells from complex human tissues to address how patterns of gene expression differ between cells within a single tumor and between patients with histologically similar tumors. The long-term goal of these efforts is to use state-of-the-art technology to define and further characterize patterns of gene expression that may be applied to the rationale design of new cancer diagnostics and therapeutics.