Michael F. Clarke, MD
Karel and Abice Beekhuis Endowed Professor
Professor of Internal Medicine
Associate Director of the Stem and Regenerative Medicine Institute
Palo Alto, California
2013-2014 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.
During his BCRF-funded tenure, Dr. Clarke has made an important finding that may eventually result in decreased mortality from this disease. In the last six months, his team made progress in two areas that could directly impact patient care. First, they have found a marker that appears to predict the likelihood that a woman with triple negative breast cancer will respond to therapy. With their clinical collaborators, Dr. Clarke plans to validate this marker in retrospective and prospective clinical studies. Next, his team has developed a novel technique that enables them to grow breast cancer stem cells in culture. This should greatly facilitate multiple clinical problems. These include personalized drug therapy and identification of new therapies for this poor prognosis group of patients. Dr. Clarke hopes to collaborate with other BCRF investigators to use their culture system to study metastases, which are responsible for the vast majority of mortalities in breast cancer.
After receiving his medical 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 National Cancer Institute, Dr. Clarke was the first to demonstrate that enforced expression of a normal proto-oncogene (c-sis) could lead to transformation. 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. He was also the first to demonstrate that inhibition of programmed cell death (PCD) was essential for the survival of breast cancer cells.
Most recently, Dr. Clarke's laboratory has made three important findings. He was the first to identify a molecular pathway that regulates the essential process of adult stem cell self-renewal. 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. Finally, he found that USPP16, an antagonist of BMI1 causes a stem cell defect in Down syndrome, which causes some of the pathology associated with this syndrome. Down syndrome patients do not develop breast cancer. Preliminary evidence suggests that USP16 plays a role in human breast cancer. 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.