Ovarian cancer has the highest mortality rate among the gynecologic cancer types in the United States due to the difficulties in early diagnosis, the development of chemotherapy resistance, and the dismal outcome of immunotherapy. Stress, inflammation and cell injury signals are often accompanying early tumor progression and are seen following the administration of chemotherapy. How the presence of these stress signals in the tumor microenvironment contribute to the development and progression of ovarian cancer, is not clear. Our lab has a long-standing interest in one key stress signaling molecule MK2, which has implications in the functionalities of macrophages in other types of cancer with unknown mechanisms. We will test the hypothesis that MK2 coordinates extracellular stress signals for macrophages, which in turn create a microenvironment that support ovarian cancer cells prosper and limits anti-tumor surveillance by the immune system. To test this, we will compare macrophages with or without MK2 in mouse models that reflect true origin of ovarian cancer and consolidate the results in human cells. By doing so, we will be able to understand what cell types macrophages would interact with under the influence of MK2, and what molecules make macrophages promote ovarian cancer development. The expected results will help explain how macrophages change from being anti-tumorigenic to pro-tumorigenic, identify markers for the tumor-promoting status of macrophages, and reveal MK2-related novel therapeutic targets to prevent or slow ovarian cancer development, and improve the treatment of this disease by both chemotherapy and immunotherapy approaches.
This grant was made possible in part by a generous donation from The Rock ‘n Run event.
Dr. Xueyang Yu is a postdoctoral fellow working in the laboratory of Dr. Michael B. Yaffe at Koch Institute for Integrative Cancer Research at MIT, Cambridge. She obtained her master degree in Molecular and Cellular Biology at Heidelberg University in Germany, and her Ph.D. at the Institute of Experimental Immunology at University of Zurich in Switzerland. During her Ph.D. training, Dr. Yu focused on the interplay of tissue microenvironment and macrophage heterogeneity. Her Ph.D. thesis work on the role of transforming growth factor beta (TGF-β) in the development and homeostasis of tissue-resident macrophages, became a landmark discovery in field of myeloid cell biology. With her expertise in innate immunology, Dr. Yu joined Dr. Michael B. Yaffe’s group, who has a long history of studying stress signaling and pathway cross-talk in cancer. Dr. Yu is aimed at discovering the role of stress pathways in controlling macrophage-regulated tumor microenvironment during ovarian cancer progression.