2015 Outstanding New Investigator: James Mitchell

James MitchellJames Mitchell
Associate Professor of Genetics and Complex Diseases
Harvard T. H. Chan School of Public Health
Boston, MA, USA

After graduating from the University of Virginia in 1993, Dr. Mitchell worked as a technician at Cold Spring Harbor Laboratory in Dr. Bruce Stillman’s lab for two years, where he became interested in biochemistry, the genetics of DNA replication in yeast, and fishing in the Long Island Sound. He chose biochemistry and moved to California to do his graduate studies at UC Berkeley, where he worked on human telomerase ribonucleoprotein structure and function in the lab of Dr. Kathleen Collins. There, he helped to identify the aplastic anemia syndrome dyskeratosis congenita as the first recognized telomere maintenance disorder, or telomeropathy.

Dr. Mitchell moved to Rotterdam in the Netherlands to learn mouse genetics as a postdoc in Prof. Jan Hoeijmakers’ lab, where he worked on premature aging in a DNA repair-deficient mouse models of the segmental progeria Cockayne syndrome. He found that these mice, although short-lived, display many key adaptive metabolic and physiologic features of dietary restriction, an intervention best known for extending lifespan in organisms as diverse as roundworms, fruit flies, and rodents. These studies sparked his interest in the benefits of dietary restriction and its potential translation to the clinic.

Dr. Mitchell started his own lab at the Harvard T.H. Chan School of Public Health in Boston in 2008, where the main focus remains on the use of dietary restriction to protect against acute inflammatory stressors ranging from ischemia reperfusion injury to metabolic syndrome to experimental rodent malaria. Dr. Mitchell’s team uncovered the ability of short-term dietary interventions lasting one week or less, and consisting of reduced overall food intake or reduction of specific amino acids such as methionine and cysteine, to improve outcomes in preclinical models of surgical stress. Mechanistically, these benefits require upstream nutrient sensing pathways involving amino acid sensing kinases including GCN2 and mTORC1, and novel downstream effector molecules including a beneficial product of the transsulfuration pathway, hydrogen sulfide. Dr. Mitchell’s long-term goal is to translate these findings to best practice in the clinic, beginning with the question of what we should or shouldn’t eat before the planned stress of major surgery.