Department of Nutritional Sciences &
Sandy Martin, Professor at the University of Colorado School of Medicine
University of Colorado Anschutz Medical Campus
The goal of our research is to discover the relationship between genome and phenome that underlies the remarkable physiology of hibernation. Hibernators have naturally solved many of the intractable problems that plague human medicine; we believe that decoding these solutions offers unparalleled opportunity to design new approaches that will mitigate and reverse damage from cardiac arrest, stroke, trauma, obesity, and from bone and muscle disuse atrophy. Our model organism is the thirteen-lined ground squirrel, which hibernates for about half the year. During hibernation, these remarkable mammals cycle their physiology between two extremes, torpor and arousal, with the vast majority of the time spent in torpor. To enter torpor, metabolic rate is dropped to just 5% of basal in concert with severe depression of heart and respiratory rates. Core body temperature then plummets to near freezing, further enhancing and stabilizing the metabolic depression; this extreme physiology persists for ~two weeks and then is reversed rapidly and spontaneously, bringing core temperature and metabolism back to more typical mammalian homeostatic values where they remain for about 12 hours before the animal cycles back into torpor. The process of arousing from torpor and rewarming the body more than 30◦C takes just two hours, uses only endogenous mechanisms to generate heat (first non-shivering, then shivering thermogenesis), and occurs via an internal timing mechanism without environmental warming. In sharp contrast to hibernation, during the remainder of the year these animals maintain high metabolism and body temperature continuously and do not enter torpor. Annually and prior to the onset of winter, the animals also become obese. They suddenly stop eating, and switch to burning rather than storing fat, relying on this stored fuel throughout the six months of winter hibernation. The seasonal changes that distinguish the hibernation and active phases of their annual cycle include enhanced tissue protection in organs throughout the body during winter, and transient (notably, reversible) obesity. In torpor-arousal cycles, largely unknown mechanisms protect against ischemia-reperfusion damage despite intense metabolic activation during the short, rapid rewarming phase. To gain insight into the genetic and biochemical mechanisms underlying this remarkable physiology we have exploited the key feature of timing in both the seasonal cycle and the torpor-arousal cycle by collecting a tissue bank from ~ 200 precisely- timed animals in different stages of both cycles. The bank has provided robust information about protein and metabolite changes in sync with hibernation physiology, but we have just begun to scratch the surface of what this unique resource can reveal about this extraordinary phenotype. Ongoing efforts are directed towards understanding mechanisms of neuroprotection as well as metabolic control and body weight homeostasis using RNA-seq and other modern genomics methodologies.
William J. Evans, PhD
Adjunct Professor of Human Nutrition
Department of Nutritional Sciences & Toxicology
University of California, Berkeley
One of the principal areas of my research has been the examination of the causes of late life disability. My research has examined the functional and metabolic consequences of physical activity in elderly people as well as how dietary protein and energy needs change with advancing age. I was the first to describe the condition called sarcopenia, the age-related loss of muscle mass and strength. Sarcopenia is a multifactorial problem resulting from a number of factors including decreased physical activity, decreased testosterone, estrogen, and growth hormone production, increasing insulin resistance, and poor diet. My research has also demonstrated that older people lose muscle mass and strength far more rapidly than do young people during enforced bed rest. These factors result in an increased risk of disability, falls, hospitalization, and institutionalization. The loss of muscle mass is also a common consequence of many chronic diseases such as cancer, chronic heart failure, and chronic obstructive pulmonary disease. Skeletal muscle is remarkably responsive to changes in nutritional status and physical activity. Decreased dietary protein intake can result in a rapid loss of muscle and low protein intake among elderly people may be one cause of sarcopenia. We have also demonstrated that the need for dietary protein increases with advancing age. We have developed a novel, non-invasive method to measure muscle mass in infants, children, and adults using only a single urine sample. Using this method in a large cohort study, we have demonstrated that in elderly men, muscle mass is strongly associated with increased risk of disability, hip fracture, and mortality. We are currently exploring longitudinal changes in functional muscle mass in boys with Duchenne Muscular Dystrophy and in geriatric cancer survivors.
Katherine R. Tuttle, MD, FASN, FACP, FNKF
Executive Director for Research, Providence Health Care
Professor of Medicine, University of Washington
Co-Principal Investigator, Institute of Translational Health Sciences
Katherine R. Tuttle, MD, FASN, FACP, FNKF, is Executive Director for Research at Providence Health Care, Co-Principal Investigator of the Institute of Translational Health Sciences and Professor of Medicine at the University of Washington. Dr. Tuttle earned her medical degree and completed her residency in Internal Medicine at Northwestern University School of Medicine in Chicago, Illinois. She was a fellow in Metabolism and Endocrinology at Washington University in St. Louis, Missouri. Her Nephrology fellowship training was performed at University of Texas Health Science Center in San Antonio, Texas.
Dr. Tuttle’s major research interests are in clinical and translational science for diabetes and chronic kidney disease. She has published over 200 original research contributions and served two terms as Associate Editor for the Clinical Journal of the American Society of Nephrology and the American Journal of Kidney Disease. Dr. Tuttle has received many honors and awards including the Medal of Excellence from the American Association of Kidney Patients, Garbed Eknoyan Award from the National Kidney Foundation, the YWCA Woman of Achievement Award in Science, and two Outstanding Clinical Faculty Awards at the University of Washington. Dr. Tuttle served on the Board of Directors for the Kidney Health Initiative and has chaired numerous kidney and diabetes related working groups and committees for organizations including the NIDDK/NIH, the National Kidney Foundation, the American Society of Nephrology, the International Society of Nephrology, and the American Diabetes Association.