GRANTEE: Nada Kalaany, PhD
Children’s Hospital Boston
Research Project: Role of arginine metabolism in obesity-associated pancreatic cancer
Award: 2015 Pancreatic Cancer Action Network – AACR Career Development Award (Grant funded by an anonymous foundation)
Award Period: July 1, 2015 – June 30, 2017
Dr. Kalaany earned her Bachelor and Master of Science degrees from the American University of Beirut, Lebanon. She received her PhD degree from the UT Southwestern Medical Center, where she studied the role of nuclear hormone receptors in diet-induced obesity. As a postdoctoral fellow, she worked at the Whitehead Institute for Biomedical Research at MIT where she unveiled a key role for a specific signaling pathway (PI3K/Akt) in modulating the sensitivity of tumors to dietary restriction. She joined the faculty of Boston Children’s Hospital, Division of Endocrinology at Harvard Medical School in 2011. A major focus of her lab is to investigate the mechanisms underlying the correlation between systemic metabolism and cancer, particularly that of the pancreas.
A strong correlation exists between obesity and the incidence of, and mortality from, pancreatic cancer. Experiments in mice have revealed that pancreatic cancer cells implanted into obese mice lead to larger tumors and decreased survival as compared to the same cells implanted into lean mice. However, activation of a protein called Akt within the cancer cells can mimic conditions of obesity even in lean mice. Dr. Kalaany’s research has suggested that pancreatic tumors grown under obese conditions or with activated Akt require a certain nutrient, arginine, for growth and survival.
For her proposed project, Dr. Kalaany and her research team aim to better understand how the breakdown of arginine affects pancreatic tumor growth. Studies will include cancer cells with or without activated Akt implanted into lean or obese mice, and determination of the role of various genes that are involved in the breakdown, or metabolism, of arginine. Additionally, obese or lean mice genetically engineered to develop pancreatic cancer will be fed a diet with or without arginine to determine how dietary arginine influences tumor growth. Dr. Kalaany and colleagues will apply a variety of molecular, biochemical and metabolic approaches to alter the arginine metabolic pathway within the tumor cell and also suppress its utilization by the tumors through deprivation of dietary arginine. Identifying such metabolic dependencies could lead to the development of novel anti-pancreatic cancer therapeutic strategies that could be used in combination with currently available chemotherapies.