Dorothy A. Sipkins, MD, PhD
Year elected: 2017
Current membership category: Active
Duke University Medical Center
Genome Sci Res Bldg 1 Room 4040
905 S. LaSalle St.
Durham, NC 27710
United States of America
My research focus is in understanding how cancer’s metastatic growth is regulated by specific interactions with the host microenvironment that control behaviors ranging from organ tropism, tumor dormancy and chemoresistance. While substantial research has focused on defining targets in the tumor cell itself that can affect survival or repair mechanisms, the identification and disruption of these critical tumor-host interactions represents a comparatively unexploited area. This work therefore aims to create a fundamentally different approach to combat cancer metastasis that targets the synapse between metastatic cells and the protective tissue niches they inhabit.
To study these processes, which are often rapid and rare, in real time, my lab utilizes high resolution, video rate in vivo imaging technologies. Using this approach in combination with genomic, immunohistochemical and functional ex vivo analyses of xenograft tissues and of primary human samples, we have made several novel observations. These have included the identification of a novel vascular tumor niche in the bone marrow (BM) that represents the site of metastatic tumor entry from the circulation (Nature, 2005); the first demonstration of a molecular mechanism to explain the suppression of normal hematopoiesis seen in patients with malignant invasion of the BM (Science, 2008); and the first demonstration of a molecular mechanism regulating leukemia cell quiescence within the BM niche, contributing to cancer cell chemo-evasion (Blood, 2013). In addition, our lab recently defined the key molecular interactions that control the transit of circulating breast cancer cells into and out of bone and showed that dormant breast cancer cells could be rapidly mobilized from the BM into the peripheral circulation by inhibiting a single stromal interaction (Science Translational Medicine, 2016).
Ongoing projects in my laboratory seek to define further targets that control leukemia and breast cancer cell migration, proliferation and dormancy in the BM and other metastatic sites. In addition, we are actively working to translate our findings to investigator-initiated trials in leukemia and breast cancer patients.