Stephen N. Thibodeau, Ph.D.

Stephen N. Thibodeau, Ph.D., is a professor of laboratory medicine and pathology in the College of Medicine, Mayo Clinic, and a co-director of the Molecular Genetics Laboratory, a clinical laboratory in the Department of Laboratory Medicine and Pathology. In addition, he is a member of the Division of Medical Genetics.

The main focus of Dr. Thibodeau's laboratory research is to understand the genetics of both prostate cancer and colon cancer. He and his colleagues want to answer the question: Why is it that some families have more cancers among family members when compared to other families?

Historically, in order to look for genes involved in hereditary cancer, Dr. Thibodeau and his team would examine the involvement of one gene at a time among the families under study. New DNA sequencing technologies, however, continue to evolve at such an extremely rapid rate that it's now possible to easily sequence all of the known genes simultaneously.

Over the last several years, Dr. Thibodeau's laboratory has explored the use of next-generation sequencing technologies for the discovery of genetic susceptibility genes for both hereditary prostate cancer and hereditary colon cancer.

Focus areas

• Prostate cancer genetics. Dr. Thibodeau is working to identify both high- and low-penetrant susceptibility genes for prostate cancer. Over the years, his laboratory has used both linkage-based and association-based studies for discovery gene and variant discovery.

  More recently, they have begun to use next-generation DNA sequencing (whole-exome sequencing) for the identification of genetic susceptibility loci.

• Colon cancer genetics. Dr. Thibodeau is interested in characterizing the molecular genetic changes that occur in both sporadic and familial colorectal cancer, primarily hereditary nonpolyposis colorectal cancer (HNPCC).

  Colon cancer results from various genetic changes at a number of different loci, including both dominant- and recessive-acting tumor suppressor genes. Additionally, the molecular events leading to cancer in patients having familiar colorectal cancer may share some common features with those patients having sporadic colorectal cancer.

  For HNPCC, abnormalities in a number of genes involved in DNA mismatch repair have been identified. The long-term goal of Dr. Thibodeau and his colleagues is to understand which DNA mismatch genes are involved, the types of mutations involved, the timing and sequence of these molecular changes, and their clinical significance.

  In other studies, Dr. Thibodeau's laboratory is identifying and characterizing genes that are upregulated and downregulated in colorectal cancer and determining their clinical significance.

Significance to patient care

Dr. Thibodeau's program has been committed to translational research — that is, work that can be implemented in a clinical laboratory setting for routine patient care.

As Dr. Thibodeau co-directs the clinical Molecular Genetics Laboratory in addition to overseeing his research laboratory, he and his team have been able to take advantage of the work performed in the research laboratory to develop and implement a variety of tests in the Molecular Genetics Laboratory that can be used directly for patient care.

As an example, new technologies in DNA sequencing mentioned are now beginning to be incorporated in routine clinical practice at Mayo Clinic. In addition, there are a number of clinical assays that are routinely used for the diagnosis of hereditary colon cancer.