DNAprint Genomics (DNAG)

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Not to far afield:
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Mark A. Watson, M.D., Ph.D.

Assistant Professor
Pathology and Immunology
Molecular Genetics Program
Quantitative Human and Statistical Genetics Program


Office Phone: [phone]
Lab Phone: [phone]
Other Phone:
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Box: 8118
Lab Address: 2316 Kingshighway Building, Barnes-Jewish Hospital, North
Email: [e-mail]
Website: http://pathbox.wustl.edu/~mgacore
Keywords: cancer; functional genomics; gene expression; pathogenesis; breast cancer
Short Research Description: Use of microarray technology and other 'whole-genome' approaches to molecularly classify human malignancies and to identify genetic pathways associated with tumor progression.

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.

Span PN, Waanders E, Manders P, et al. Mammaglobin is associated with low-grade, steroid receptor-positive breast tumors from postmenopausal patients, and has independent prognostic value for relapse-free survival time. J Clin Oncol 2004 22:691-698.

Ley TJ, Minx PJ, Walter MJ, et al. A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes. Proc Natl Acad Sci USA 2003 100:14275-14280.

Gutmann DH, Hedrick NM, Li J, et al. Comparative gene expression profile analysis of neurofibromatosis 1-associated and sporadic pilocytic astrocytomas. Cancer Res 2002 62:2085-2091.

Luizzi V, Holtschlag V, Watson MA. Expression profiling of ductal carcinoma in situ by laser capture microdissection and high density oligonucleotide arrays. Am J Pathol 2001 158:278-284.

Fleming TP, Watson MA. Mammaglobin, a breast-specific gene, and its utility as a marker for breast cancer. Ann N Y Acad Sci 2000 923:78-89.

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