Comparative Muscle Physiology
  I am generally interested in the physiology of vertebrate skeletal and cardiac muscle, and in particular, the myosin heavy-chain contractile protein. Myosin is the major force producing component of muscle, and has many functionally different isoforms; each protein is a distinct gene product and is differentially expressed in individual muscles. The control of myosin protein expression is complex, and is very sensitive to activity, temperature, and hormone influences. Skeletal muscle and the heart are both affected by exercise, resistance training, and other factors, which may dramatically change the muscle size and myosin heavy chain composition. I am most interested in shifts or transitions in myosin protein expression with increased activity, or conversely, with disuse.

  As a proponent of the comparative approach, my laboratory investigates a wide variety of vertebrates, each of whom demonstrates some remarkable aspect of muscle physiology. The techniques involved are elementary to muscle physiology and molecular biology, but are somewhat novel in their application to these diverse organisms. Protein gel electrophoresis is useful for measuring the expression of myosin isoforms in individual muscles, or even individual muscle fibers. Reverse-transcriptase polymerase chain reaction (RT-PCR) allows estimation of the mRNA expression of each myosin gene, and in general, myosin genes from new species are sequenced where possible.

Hibernating Mammals
  Hibernating mammals present many interesting opportunities to study muscle biology. Many mammals, from orders as diverse as rodents, bats, bears, and even primates, spend months in a state of lowered metabolism and reduced physical activity. In the few instances where it has been investigated, the muscles of these hibernators demonstrate the remarkable ability to withstand disuse atrophy and a loss of oxidative metabolism. I have studied this in golden-mantled ground squirrels, two species of prairie dogs, and black bears, using SDS-PAGE, and after cloning the myosin genes, RT-PCR. Myosin expression is altered following up to 6 months of inactivity, but in the direction of more oxidative, fatigue-resistant isoforms, uncharacteristic of disuse in non-hibernators. My lab continues to work on the possible transcriptional control and environmental factors that influence hibernating muscle phenotypes.

Snake Cardiovascular Response to SDA
  An increase in postprandial metabolism has been well documented in carnivorous lizards and snakes. Pythons were reported to undergo a rapid upregulation of many tissues, including an enlargement of the heart, to support the increased metabolic demands. With collaborators James Hicks, Albert Bennett and Johnnie Andersen at UC Irvine, we have recently demonstrated a remarkable 40% hypertrophy of the python ventricle within two days of consuming a large meal (25% of body mass). We are now examining the possible hormonal triggers to this hypertrophy, and continue to characterize the cardiovascular contribution to the metabolic response. We have sequenced the myosin genes from the heart of Python molurus, and are using molecular techniques to examine the response of other tissues as well.

Reptile Exercise and Muscle Response
  In mammals, increased aerobic exercise generally causes an enlargement of skeletal muscle, and an increased accumulation of type I or type IIa myosin heavy chain. Reptiles, such as the carnivorous Varanus exanthematicus, may go several months without activity during the dry season, and yet may suffer no disuse atrophy of skeletal muscle. With Amanda Szucsik at UC Irvine, we are looking at how exercise and immobilization affect the myosin isoform protein and mRNA expression in the relatively aerobic Varanus species.

Myosin Evolutionary Genetics
  As we accumulate more myosin sequences from skeletal and cardiac muscle of a variety of vertebrates, we are examining the evolutionary genetics of myosin as the new groups are cloned. New sequences are used to develop PCR primers to measure mRNA expression of the isoforms, and to analyze patterns of sequence divergence. This is now expanding into marine organisms for which little sequence information is available, including elasmobranch fishes and additional teleost species.