Jeffrey Charles Rathmell
Adjunct Associate Professor in the Department of Pharmacology and Cancer Biology

My laboratory studies the mechanisms and role of glucose metabolism in lymphocyte survival and activation. We have found that dramatic increases in glucose metabolism are necessary for lymphocytes to survive and mount immune responses. Excessive glucose metabolism, however, can lead to T cell hyperactivation and autoimmunity. A key mechanism for control of lymphocyte glucose metabolism is regulation of glucose uptake by the glucose transporter, Glut1. Interestingly, upregulation of Glut1 and glucose metabolism has also long been observed in cancer cells of all varieties and this may play an important role in cancer cell growth and survival. It remains unknown, however, how Glut1 expression or localization is regulated and how alterations in glucose uptake may affect immunity or cancer. To address this issue we are taking three approaches.

(1) Determine the signal transduction mechanisms that regulate Glut1 expression and intracellular trafficking.
(2) We have generated Glut1 transgenic mice that express Glut1 specifically in T cells and are making a conditional Glut1 knockout mouse to study the role of glucose uptake in T cell activation and regulation of Bcl-2 family proteins.
(3) We are also addressing how alterations in glucose uptake may affect development of cancer and if leukemias may become “metabolically addicted” to high glucose metabolism.

Our approach of studying the mechanism and role of metabolic regulation in lymphocytes bridges immunology and metabolism research. Ultimately, understanding this problem may lead to new metabolic approaches to immune and cancer therapies.

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