This is a summer student position supervised by Younghwan Lee from Karen Vousden's lab.
Introduction to the Science
Metabolic reprogramming is a hallmark of cancer which provides unique vulnerabilities for the selective targeting of cancer cells. However, these vulnerabilities can be affected by the surrounding tumour microenvironment (TME), which can support the nutritional demands of cancer cells and cause differential responses to metabolism-targeted therapies .
About the Project
Obesity can induce the accumulation of adipocytes in the TME around the tumour. However, how obesity affects tumour progression is unknown. One way in which obesity might effect tumour progression, is via the promotion of systemic oxidative stress. Oxidative stress is defined as an imbalance between the production of reactive oxygen species (ROS) and the antioxidant capacity of the cell. Although obesity has also been shown to increase ROS and drive metabolic changes in adipocytes, how ROS affects the interaction of adipocytes with cancer cells is unknown.
The proposed work will investigate whether and how adipocytes support the metabolic demands of cancer cells and how mitochondrial ROS affects adipocyte interaction with cancer cells. We are going to employ mitochondria-targeted chemical modulators of ROS and genetic modulation of TIGAR (an antioxidant protein that has been shown to limit ROS), as our previous work showed a role for TIGAR in regulating ROS and Pancreatic ductal adenocarcinoma cells metastasis .
The work in our laboratory is focused on how nutrient availability and metabolism effect cancer development. For this project, we are looking for a summer student who has an interest in cancer cell biology and metabolism. The summer student will investigate how mitochondrial ROS controls the interplay between cancer cells and adipocytes usingcell and molecular biology techniques.
1. Lyssiotis, C.A. and Kimmelman, A.C. (2017)
Metabolic interactions in the tumor microenvironment.
Trends in Cell Biology 27: 863-875. PubMed abstract
2. Cheung, E.C., DeNicola, G.M., Nixon, C., Blyth, K., Labuschagne, C.F., Tuveson, D.A. and Vousden, K.H. (2020)
Dynamic ROS control by TIGAR regulates the initiation and progression of pancreatic cancer.
Cancer Cell 37: 168-182 e164. PubMed abstract