Mark Bothwell PhD
University of Washington
Physiology and Biophysics
My main interest is the regulatory function and signaling mechanisms of growth factors in embryonic development, and particularly, the role of neurotrophins and other growth factors in mediating trophic interactions in the developing nervous system. Other research interests concern control of processing and turnover of the beta-amyloid precursor protein in the context of Alzheimer's disease and the function of a cilia-associated protein, prominin-1, in stem cells.
In the realm of growth factor signaling, we presently have two major foci. First, we are studying a family of membrane proteins, LIG proteins, various members of which either enhance, or inhibit signaling by a variety of growth factor receptors. Growth factor receptors are turned over by endocytosis leading to lysosomal degradation. Our working hypothesis is that different LIG proteins promote, or retard the delivery of receptor-bearing endosomes to lysosomes. We find that LIG proteins also control the turn-over of beta-amyloid precursor protein. Second, we are studying the signaling mechanism of the neurotrophin receptor, p75NTR and its homologs, NRH and Troy. We have observed that signaling by dimeric forms of these receptors requires formation of a unique disulfide linkage within the transmembrane domain.
We have a growing interest in the function of primary cilia, and in the stem cell marker CD133/prominin-1, which is enriched in the membrane of cilia. We have observed that prominin-1 is physically associated with several cytoskeletal proteins, as well as with an enzyme that controls DNA synthesis. We wish to know whether these interactions are important for regulation of the polarity and self-replication of stem cells. We also are interested in the role cilia play in controlling the polarity and migration of neural progenitor cells and neurons.