Project Title: Decreasing methionine intake to improve survival in patients with metastatic melanoma
Isabelle Racine Miousse, Ph.D., is an Assistant Professor in the Department of Biochemistry and Molecular Biology in the UAMS College of Medicine. The KL2 Mentored Research Career Development Award will support her research in improving survival in patients with metastatic melanoma by exploiting a metabolic vulnerability in cancer cells.
In healthy animals, a reduction in methionine dietary intake leads to significant gains in metabolic health and an increase in lifespan. In contrast, most cancer cells are strictly dependent on the supply of exogenous methionine for survival, a phenomenon called “methionine dependence”. Based on this dichotomy, her project explores a window of methionine intake where we observe health benefits and preservation of body weight for the host, while at the same time impairing proliferation and metastasis in tumor. The three axes of the project are to link common genetic variations in methionine metabolism with the outcome of cancer therapy, to identify the molecular mechanism behind methionine dependence in cancer cells, and finally, to combine dietary methionine restriction with immunotherapy in metastatic melanoma. The long term objectives of this research is to increase the response rate to therapy with immune checkpoint inhibitors in metastatic melanoma, which currently stands at 50%, while at the same time improving quality of life in patients during the course of treatment.
Miousse joined the College of Medicine faculty in 2018 after completing her postdoctoral fellowship at UAMS. She received her doctorate in Human Genetics from McGill University in Montreal, Canada.
Mentors:
Alan Tackett, Ph.D., Scharlau Family Endowed Chair for Cancer Research; Associate Director for Basic Research, Winthrop P. Rockefeller Cancer Institute; Professor, Biochemistry and Molecular Biology, UAMS College of Medicine
Issam Makhoul, M.D., Director, Division of Hematology Oncology; Professor, Internal Medicine, UAMS College of Medicine