Our research focuses on how tumor cells and “normal” cells interact with each other in the tumor organ. By doing so, we hope to generate next generation of anticancer drugs that can attack cancer on multiple fronts.
Research Interest and Activities
A tumor’s ability to proliferate, resist apoptosis, invade and thwart the immune system is the essence of cancer. Although many anti-cancer therapies show promise, most are aimed at the tumor cell as an independent entity and ignore the importance of the many cell types that constitute the tumor microenvironment. An emerging picture of the tumor as an organ highlights the role of multiple tumor-associated cells, including fibroblasts, endothelial cells, hematopoietic cells/immune cells and stem cells, that interact intimately with the transformed cells in modulating the oncogenic process.
My group has shown that Stat3, which is constitutively-activated in tumor cells, is also persistently activated in normal cells associated with the tumor. We have further demonstrated that Stat3 signaling coordinates multiple levels of crosstalk between tumor cells and their microenvironment, affecting tumor growth, apoptosis, angiogenesis and immune surveillance.
Our work, along with other studies, has established that Stat3 in tumor cells regulates a large array of genes important for proliferation, survival, angiogenesis, invasion/metastasis and immune suppression. Its central role in organizing the tumor microenvironment makes Stat3 a promising target both in tumor cells and in the normal cells that constitute the tumor organ.
The goal of my program is to use novel technologies to target Stat3 in the entire tumor, thereby inducing its collapse through multiple mechanisms, while sparing cells in the normal organs.
Identifying the Connection between Stat3 and Diabetes
It has long been established that obesity is a major cause of type 2 diabetes, due in part to specific cells in fat tissue that promote pathogenic T cells and blunt the activity of insulin. Dr. Yu is exploring the connection between Stat3 and the development of diabetes. In efforts to learn more about this potential link, her lab has used genetically-engineered mice whose T cells lack the Stat3 gene. When these mice became obese through forced consumption of a fatty diet, they showed better glucose tolerance compared with comparably overfed normal mice, as well as a shift in the balance of pathogenic T cells toward regulatory T cells. These intriguing findings suggest that Stat3 is common to both cancer and diabetes and suggest that anti-Stat3 therapies, which have thus far been considered primarily for cancer, might also be effective against type 2 and perhaps type 1 diabetes.
