During embryogenesis, a cluster of apparently undifferentiated cells is transformed into an ordered array of differentiated tissues. Using Drosophila as a model system, Dr. Albert Courey's research group combines biochemical and genetic approaches to study the molecular basis of this amazing transformation. Essentially, all the regulatory circuits they study are conserved throughout the animal kingdom. Their studies therefore have important implications for human health and development.
Courey and his colleagues have been extensively examining mechanisms of activation and repression by the Dorsal morphogen, a transcription factor that determines the dorsal/ventral axis during early development. This factor is the Drosophila homolog of the vertebrate regulatory protein NF-kB. Like Dorsal, NF-kB is involved in both the determination of embryonic polarity and in the innate immune response. Furthermore, both Dorsal and NF-kB are regulated by homologous signal transduction cascades that control transcription factor activity by regulating nuclear import.
Sumo is a recently discovered member of the ubiquitin family that is conserved throughout all eukaryotes. This polypeptide is a substrate for a protein conjugation system, in which Sumo becomes covalently attached to numerous target proteins, modifying their behavior in various ways. Courey's lab team studies the roles of Sumo in cell biology and development. Their analysis has revealed possible roles for this process in regulated nuclear import, embryonic pattern formation, the immune response and the stress response.
Selected Cancer-Related Publications:
Ratnaparkhi GS, Jia S, Courey AJ. Uncoupling dorsal-mediated activation from dorsal-mediated repression in the Drosophila embryo. Development. 2006; 133(22): 4409-14.
Bhaskar V, Smith M, Courey AJ. Conjugation of Smt3 to dorsal may potentiate the drosophila immune response. Mol Cell Biol. 2007; 22:492-504.
Chen G, Fernandez J, Mische S, Courey AJ. A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in drosophila development. Genes Dev. 1999; 13:2218-2230.