Paul N. Adler, PhD
Genetics of cell polarity and relationship to tissue structure and uncontrolled growth
Research in the Adler laboratory focuses on cell polarity and its relationship to tissue structure and development. Two distinct regulatory pathways have been studied in depth using the Drosophila model system. One of these is the frizzled planar polarity pathway. In both vertebrates and invertebrates this pathway shares about half of its components with canonical wnt pathways. Mutations in many of the genes in these pathways (both loss and gain of function) are often found in human cancers. Current studies are directed at understanding how protein components of this pathway become polarized within epithelial cells, how they functions to control the cytoskeleton and how the two types of wnt/fz pathways function separately in the same cell. The second pathway studied in the lab is the tricornered/furry pathway, which controls cell shape and the morphogenesis of cellular extensions such as dendrites and sensory bristles. The Tricornered kinase needs to bind to adapter proteins of the Mob family to function. The lab has recently found that mutations in the Mats adapter protein (a Mob family member) leads to the inactivation of both the trc/fry pathway and the warts/lats pathway. The warts/lats gene encodes a related kinase that functions as a tumor suppressor in both flies and mammals. Mutations in warts/lats also lead to cell morphology defects that are the opposite to those of trc. This suggests that these two kinase modules may regulate one another. A major focus of future research in the lab will be directed toward determining if the uncontrolled growth is a cause or an effect of the altered cell morphology. The lab will also focus on determining the relationship between these kinases pathways.
The central facilities supported by the cancer center play an important role in the activities of the lab. Hybridomas isolated at the Lymphocyte Culture Center have and continue to play a key role. For example, the monoclonals isolated at the center were absolutely essential for the recent Adler lab paper in Curent Biology. The molecular biology core facility has been used extensively by the lab for DNA sequencing. In recent years this has been used primarily for the sequencing of constructs used in generating transgenic animals, in constructs used to express fusion proteins and for constructs used in 2-hybrid experiments. The lab has also made use of the gene expression lab to characterize the transcriptome of relevant cell types. In the past they have also used the electron microscope facility to look at ultrastructural changes in mutants and to show that the Frizzled protein was a transmembrane protein.