Research Interests

Lab Research and Objectives:

            The ultimate goal of my research is to understand how cells that migrate during animal development are directed to their proper destinations. Numerous cell types migrate extensively from their sites of birth to adopt positions critical for normal animal development. Such cell movements accompany prominent events in early vertebrate development. During an early developmental stage called gastrulation, large-scale cellular rearrangements are essential for establishing tissue types. Later in development, many cell and tissue types are positioned properly within the animal by cell migrations. For example, in mammals, primordial germ cells move to the gonad, precardiac cells migrate to the heart, and muscle precursors migrate into the developing limb. In the developing mammalian nervous system, neurons migrate to generate the layers of the cerebral cortex, and neuronal growth cones migrate to their synaptic targets, an essential step in achieving connectivity. Given the diverse array of processes in which cell migration is necessary, it is critical that we have a detailed molecular understanding of the proteins involved and the pathways through which they act.

            The importance of cell migration is also highlighted by the many human developmental disorders that occur when proper migration fails. For example, defective cell migration can lead to Hirschsprung’s disease, an intestinal disorder, lissencephaly, a brain development disorder, Kallman syndrome, another brain development disorder, or congenital heart defects. Furthermore, cell migration underlies cancer metastasis, in which cancer cells migrate within the body to establish secondary tumors. This ability of cancerous cells to metastasize is often the factor that makes cancer so serious. Because metastatic cells utilize many of the same proteins as other migrating cells, elucidating the mechanisms of directed cell migration offers the potential for greater understanding of diverse developmental disorders and for developing new cancer therapies.

            The underlying molecular mechanisms that help guide the process of cell migration include cellular signal transduction cascades. Many developmental decisions are mediated by signals that are transduced between cells. In classical signal transduction pathways, extracellular ligands produced by one cell bind to cell receptors on the surface of another cell to ultimately produce changes in the activity of specific targets within the receiving cell. Most cells have a multitude of signaling receptors and molecules that act in a complex interwoven network within cells. The importance of these signal transduction cascades is evidenced by the fact that many cancers have altered activity in one or more components of these cascades. Therefore elucidation of the molecular mechanisms underlying signal transduction is fundamental to controlling tumor progression. 

            To investigate complicated biological problems like cell migration, we often utilize “model organisms”, such as the fruit fly, nematode or mouse. These animals offer several advantages including short life cycles, ease of culture and the availability of many genetic and molecular tools for deciphering biological processes. Within model organisms, each system has its own set of advantages and disadvantages. We have chosen to study cell migration in the small nematode, Caenorhabditis elegans, for several reasons. Individual migratory cells can be identified readily either by differential interference contrast microscopy or by use of the numerous cell-specific markers that are available. Additionally, the complete genome sequence is known, which greatly facilitates the identification of genes that are involved in the process of interest. C. elegans can also be transformed easily to produce transgenic animals, which are necessary to study protein function in the living organism. Finally, because many of the proteins required for cell migration are conserved between C. elegans and mammals, information learned about cell migration in C. elegans is relevant to other organisms.