Science Center K200A
Personal Office Hours:
- BSE, University of Pennsylvania, 1984
- Doctor of Philosophy, University of Washington, 1990
Teaching Area: Physiology - the study of how molecules, cells, organs, and organisms function
I teach three courses, each of which seeks to develop students' mastery of physiological concepts, understanding of the experimental evidence supporting these concepts, and ability to design meaningful experiments. Animal Physiology (Biol 312), which is given in the fall, examines the function of the body from molecular to oganismal levels and considers topics ranging from the communication between cells to the adaptations of animals to pregnancy or to extreme environments. Cell Physiology (Biol 313), taught in the spring, concerns the vibrant activity of cells and focuses on the intracellular machinery and signaling pathways supporting this activity, with examples drawn from developmental biology, immunology, and cancer biology. Cell Physiology Research (Biol 314), the third course, seeks to introduce students to the methods of research, from the formulation of an experiment to the presentation of findings and conclusions. Students work in pairs on a problem selected in consultation with the teacher and gain proficiency in one or more methods drawn from recombinant DNA technology, genetics, and cell biology.
Research Interests: Contraction of Muscle and Its Regulation
Before reading about my research interests, here's an experiment to do on yourself: hold a tennis ball in your hand and determine how many times you can squeeze the ball.
If you are like most people, you'll probably manage a total of about 100 squeezes, much less than the number of contractions your heart probably will tirelessly make in your lifetime (on average, about 2,500,000,000 beats!).
Research in my laboratory addresses how skeletal and cardiac muscles turn force production on and off, as well as how individual muscles gain unique contractile characteristics, such as the heart's ability to contract repeatedly for a seemingly indefinite period of time. At the simplest level, muscle has two components: a motor capable of transforming chemical energy (ATP) into mechanical work (force generation and shortening of muscle cells), and a calcium-sensitive switch for the motor. The four proteins forming the switch have been known for 25 years; however, the way they work is largely a mystery. Mutations in the switch proteins can cause lethal heart disease in humans and improper muscle development in the nematode Caenorhabditis elegans and the fly Drosophila melanogaster.
Such knowledge, if it were available, would guide pharmacologists and physicians in the treatment of muscular diseases, e.g., the weakened heart of an elderly patient, for whom stronger, perhaps more rapid heart beats might be desired.
To clarify how the switch mechanistically work, we are engineering mutations in genes that code for proteins in the switch, transferring the mutant genes into C. elegans, and then examining the consequences of these mutations to muscle function in C. elegans. By systematically mutating the genes, we shall be able to map particular functions of the switch (e.g., controlling the speed of contraction) to discrete protein surfaces. Such knowledge will enable drug designers to produce drugs that most effectively treat various muscular disorders.