2017 GRANTEE: Jason Doles, PhD
Research Project: Metabolic Alterations Driving PDAC-associated Muscle Wasting
Award: 2017 Pancreatic Cancer Action Network – AACR Career Development Award
Award Period: July 1, 2017 – June 30, 2019
Dr. Doles earned an AB degree in political science and biology from Brown University in 2003. In 2010, he received his PhD from the Massachusetts Institute of Technology, where he studied genetic mechanisms of chemotherapeutic resistance with Dr. Michael Hemann. As a postdoctoral fellow, Dr. Doles transitioned to adult stem cell research with Dr. Bill Keyes at the Centre for Genomic Regulation (Spain) and with Dr. Bradley Olwin at the University of Colorado-Boulder. He joined the Mayo Clinic as an assistant professor of biochemistry and molecular biology in 2016. His lab currently studies adult stem cell dysfunction in skeletal muscle wasting disorders.
Cachexia is a devastating muscle and fat wasting syndrome that affects many individuals with chronic disease, especially cancer. Pancreatic cancer patients are particularly at risk, with up to 70 to 80 percent exhibiting significant muscle wasting. This is a troubling statistic, given the correlation between muscle wasting and poor patient outcomes, including mortality, morbidity, response to chemotherapy and surgical prognosis. Despite decades of extensive preclinical and clinical research, therapeutic options for cachexia are limited.
Dr. Doles’ team aims to understand how muscle repair and regeneration are impaired in pancreatic cancer-associated cachexia. This proposal focuses on skeletal muscle stem cells, or satellite cells, and how they respond to cachexia-related (cachectic) stimuli. Mounting evidence suggests that tumor-derived secreted factors can directly impair satellite cell function by altering satellite cell metabolism. Research in the group will 1) identify and characterize novel cachectic factors and 2) elucidate how these factors disrupt satellite cell energy metabolism and muscle regeneration.
Together, these studies will reveal how systemic metabolic changes elicited by pancreatic cancer impact skeletal muscle stem cells. The results will likely provide insight into interventions that reduce muscle wasting and improve pancreatic cancer-associated mortality, therapeutic outcomes and quality of life.