The Metastasis Genetics Section (MGS) seeks to define how naturally occurring, hereditary variation present in the general population alters susceptibility to aggressive, fatal forms of prostate and breast cancer, and why similar tumors can have highly divergent outcomes in different people or families. It is estimated that over 29,000 males in the United States will die from prostate cancer in 2014, making it the second-leading cause of cancer-related death in men. The MGS is using mouse models of prostate cancer to define specific genetic differences that make certain people more susceptible to fatal forms of this disease. Through selective breeding, genetic changes that cause prostate cancer are introduced into mice of different strains, akin to races or families in humans. Differences in the growth rate of the primary tumor and spread of the tumor to distant organs (metastasis) are then measured in each of these different mouse strains. Through the use of these approaches, the section has been able to identify multiple genes, called modifier genes, in the mouse genome that drive the development of more aggressive forms of prostate cancer. They then explore the role of these candidate modifier genes in aggressive prostate cancer by comparing these genes to genes suspected of playing a role in human prostate cancer patients.
Over 40,000 women will succumb to breast cancer in the United States in 2014. Human breast cancers can be distinguished by the levels of genes they express, which makes it possible to determine which tumors are the most likely to metastasize. The goal of the section's breast cancer studies is to comprehensively evaluate the mechanisms by which specific genetic differences influence the expression levels of genes that are of importance in breast cancer metastasis. This project builds on earlier work that identified seven candidate genes that modulate breast cancer metastasis. The section has focused on two of these genes to determine how these modifier genes influence this process. These projects clearly demonstrate how modifier genes contribute to human disease.
Dr. Crawford obtained his M.B. Ch.B. degree (M.D. equivalent) from the University of Liverpool, United Kingdom, in 1998 and his Ph.D. from the University of Louisville, in 2004. Dr. Crawford's current work reflects his longstanding interest in the influence of germline variation on human disease. He served as Price Fellow for Surgical Research in the Department of Surgery at the University of Louisville from 2001 to 2004. There, he used molecular epidemiological techniques to characterize the influence of the germline on the development of inflammatory bowel disease.
Following this, he performed his postdoctoral fellowship in the laboratory of Kent Hunter, Ph.D., National Cancer Institute, Bethesda, Maryland, from 2004 to 2009. His studies concentrated on the influence of germline variation on breast cancer metastasis, where he identified germline regulators of metastasis-associated extracellular matrix (ECM) genes, which are frequently dysregulated in both mouse mammary tumors and human breast carcinomas prone to metastasis. Expression correlation analysis identified seven candidate genes with expression highly correlated to that of metastasis predictive ECM genes. He has be a tenure-track investigator in the National Human Genome Research Institute since September 2009.
Dr. Crawford has won a number of awards and honors, including an American Association for Cancer Research Scholar-in-Training award in 2007.
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Last Reviewed: January 5, 2015