My initial research interests focused on cytoskeletal changes in neuronal growth cones at the tips of outgrowing nerve fibers as they navigated through their environment. Outgrowing nerve fibers were studied in cultured neurons where live cell imaging was used to record changes in growth cone dynamics. Reorganization of actin filaments and microtubules that determine growth cone structure and motility was visualized using fluorescent cytoskeletal analogs that incorporate into cytoskeletal polymers. Dynamic flow of actin filaments in growth cone lamellipodia at their leading edge was studied with the technique of fluorescent speckle microscopy, which utilizes low-level, stochastic incorporation of fluorescent analogs into the actin filament network. Similarly, microtubule extension into growth cones was studied simultaneously to visualize the interaction between actin filaments and microtubules that forms the basis of growth cone turning.

In current experiments, we have applied the technique of fluorescent speckle microscopy to study formation of the spindle during meiosis. focused on the dynamics of microtubule assembly in spindles during the process of meiosis using live imaging of fluorescent labeled microtubules. We utilized cranefly spermatocytes isolated into acute cultures containing cells at various stages of cell division that can be studied for several hours. Microtubule dynamics are studied by the technique of fluorescent speckle imaging whereby spermatocytes are injected with low concentrations of fluorescent-labeled tubulin that incorporates into microtubules at low density. This creates a patterned, discontinuous labeling of microtubules that enables quantification of the rates and sites of assembly. Our experiments examined the role of tension as a modulator of microtubule polymerization during anaphase of cell division. Chromosome kinetochores exert dragging forces on attached microtubule ends favoring microtubule assembly as chromosomes move from spindle equator to spindle poles. However, microtubule disassembly is induced when dragging forces are eliminated by laser ablation of attached chromosomes. These observations reveal some of the self-organizing mechanisms that control the orderly separation of chromosomes during cell division.



Current work is devoted to creating specimens for the Brain Museum in the Jacobs School and maintaining its collection. This is a resource for our medical students learning about the brain and for visitors to the school. It provides a unique opportunity to see a human brain.

As part of my commitment to teaching, I also am course director for the Neuroscience and Behavior module for second year medical students. I have developed numerous teaching materials, including a dedicated web site. I have recently made major organizational changes to the teaching format of the module to emphasize self-directed learning and problem-solving