Alteration of Folic Metabolism in Breast Cancer.

摘要

My postdoctoral research focuses on alteration of folate metabolism in breast cancer. The connection between folate metabolism and breast cancer has long been recognized. Paradoxically, we know relatively little about the basic science of folate metabolism in the context of breast cancer. We do not yet know whether folate metabolism is altered in breast cancer compared to normal mammary tissues, and whether this alteration can contribute to breast cancer pathogenesis. These are important questions to be addressed in my research. Our central hypothesis is that either direct mutations of folate metabolic enzymes, or altered signal transduction pathways in breast cancer (such as PI3K pathway hyperactivation), leads to altered folate metabolism, which in turn contributes to the uncontrolled cell growth seen in breast cancer. In this fellowship period (Year 1), I have been investing in developing key methodologies that are essential for studying alteration of folate metabolism in breast cancer. Notably, I have successfully developed and validated a robust HPLC method that permits quantitative assessment of intracellular folates and capturing of the dynamics of their interconversions upon various stimuli, thus paving the way for future endeavors in testing specific hypotheses. I have presented part of this project in the poster session of the 2014 FASEB Folic Acid, Vitamin B12, and One- Carbon Metabolism conference. We hope that by gaining basic knowledge of folate metabolism, we can build a firm foundation for rational design of therapeutics and for early detection and diagnosis of breast cancer.