Michael F. Clarke, MD
Professor of Internal Medicine; Karel and Abice Beekhuis Endowed Professor; Deputy Director of the Stem and Regenerative Medicine Institute
Stanford University, Palo Alto, CA
2008-2009 BCRF Project:
Dr. Clarke's laboratory was the first to identify breast cancer stem cells, a minority population of cancer cells which are responsible for the growth and spread of breast cancer to distant sites. These cells are ultimately responsible for cancer-related death in women with this disease.
BCRF support has enabled his team to make three important findings that may eventually result in decreased mortality from this disease. First, using a fingerprint derived from breast cancer stem cells, the Clarke laboratory has identified a new way to identify women with early stage breast cancer who are at increased risk of relapse. This may allow researchers to better identify women who do, or just importantly do not, need adjuvant therapies. Next, they have identified a new way in which breast cancer stem cells escape specific treatments. This has allowed them to identify a potential drug that can make cancer stem cells sensitive to radiation. This could allow more effective treatment of women with radiation. Finally, the researchers have potentially identified a novel mechanism by which breast cancer stem cells maintain themselves and spread to distant organs. Again, this may lead to new therapeutic strategies for this disease.
Bio:
After receiving his MD degree from Indiana University, Dr. Clarke was an Oncology Fellow at the National Cancer Institute. In 1986, he joined the faculty at the University of Michigan where he was Professor of Internal Medicine and Professor of Cell and Developmental Biology. In the fall of 2005 Dr. Clarke moved to Stanford University where he directs the solid tumor cancer stem cell program and serves as Associate Director of the Stem and Regenerative Medicine Institute.
While a post-doctoral fellow at the NCI, Dr. Clarke was the first to demonstrate that enforced expression of a normal proto-oncogene (c-sis) could lead to transformation (Clarke, et al. Nature , 308: 1984). While at the University of Michigan, Dr. Clarke has made several discoveries relevant to cancer. He was the first to demonstrate that an alternatively spliced proto-oncogene mRNA (mbm2) could function as a dominant-negative inhibitor of the proto-oncogene (Weber, et al. Science, 249: 1990). He was also the first to demonstrate that inhibition of programmed cell death (PCD) was essential for the survival of human breast cancer cells (Clarke, et al. PNAS, 92: 1995).
Most recently, Dr. Clarke's laboratory has made two important findings. He was the first to identify a molecular pathway that regulates the essential process of adult stem cell self-renewal (Park, et al. Nature. 43: 2003). Next, he has found that not all cancer cells found in solid tumors have the capacity to self-renew and form new tumors. His laboratory has developed methods to prospectively identify this "cancer stem cell" population in breast cancer (Al-Hajj, et al. PNAS 7: 2003). These findings have linked the process of self-renewal in normal stem cells to cancer. These observations have implications for the treatment and diagnosis of human cancers. The focus of the laboratories research efforts are directed at the identification and eradication of breast cancer stem cells, the cells that drive the growth and metastasis of these tumors.
