Office: Biology 217
Phone: (970) 491-0782
My research combines my expertise in exercise and skeletal muscle physiology with molecular techniques to focus on oxygen metabolism; especially on the control and regulation of skeletal and cardiac muscle adaptations to extreme environmental conditions such as hypoxia. The ultimate goal is to enhance our understanding of molecular changes associated with hypoxia and translate these results for therapeutic applications in the treatment of myopathies. One aspect of this research explores the regulation of the physiological and metabolic adaptations of marine mammals to an aquatic lifestyle. Air-breathing diving vertebrates, especially those that make deep and long dives, exhibit physiological adaptations in their muscles (and other tissues) that sustain an aerobic, lipid-based metabolism under extreme conditions of hypoxia and ischemia. These adaptations increase an animal's aerobic dive limit (ADL), which is the longest dive that an animal can make while relying primarily on oxygen stored in the blood and muscle to sustain aerobic metabolism. Our previous studies of adult Weddell seals, harbor seals and Steller sea lions have shown that these muscle adaptations include: 1) an increased aerobic capacity (or one that is matched to routine levels of exertion), 2) a reliance on fatty acid catabolism for aerobic ATP production, 3) enhanced oxygen storage and diffusion capacity, and 4) a reduced dependency (e.g., decreased capillary density) on blood-borne oxygen and metabolites compared to terrestrial mammals. My current and future research builds on these results to investigate the ontogeny of these adaptations and the genetic control of their development. One objective is to characterize the ontogenetic changes in aerobic capacity, lipid metabolism, fiber type, and myoglobin concentration using enzymatic, immuno-histochemical and myoglobin assays in newborn, newly weaned, subadult, and adult seals. The second objective is to determine the molecular controls that regulate these changes during maturation. Through subtractive hybridization and subsequent analysis, we will determine the differences in mRNA populations in the swimming muscles of the different age classes of seals. These techniques will allow us to identify the proteins and transcription factors that influence the ontogenetic changes in myoglobin concentration, aerobic capacity and capillary density in skeletal muscle. The other major focus of my research is on oxygen metabolism and the transcriptional regulation of myoglobin and fiber type differentiation. Specifically this research investigates the importance of calcium signaling and the calcineurin/NFAT pathway on skeletal and cardiac muscles during exercise under normoxic and hypoxic conditions. This work utilizes a multidisciplinary approach which incorporates cell culture, biochemical, calorimetric and histological techniques along with transgenic mouse models.