The major research interest of our laboratory is the genetic control of the development and behavior of the nematode Caenorhabditis elegans, with the goal of understanding fundamental aspects of biology and revealing insights into human disease.  The general approach of our laboratory is to identify genes that control important biological processes and analyze molecular and cellular pathways identified by these genes.  Our major long-term areas of interest have been programmed cell death, cell lineage and cell fate, animal behavior, responses to hypoxia and other stresses, cancer, and neurodegenerative disorders (e.g., amyotrophic lateral sclerosis).  Specific problems of current interest include: (1) the pro-apoptotic function of the normally anti-apoptotic protein gene ced-9 (homolog of mammalian Bcl-2), and the anti-apoptotic function of the normally pro-apoptotic gene ced-4 (homolog of mammalian Apaf-1); (2) the mechanism by which the chromatin cohesion protein cohesin controls the development of a subset of GABAergic neurons; (3) how an animal without either eyes or opsins senses distinct specific colors of light and the molecular, cellular and neural-circuit bases of how a set of mechanosensory neurons mediates behavioral responses to colored light; (4) memory and learning, including mechanisms responsible for temporal pattern recognition and trace-conditioning (a form of classical conditioning sometimes associated with awareness) in a novel paradigm for associative learning; (5) the molecular genetic mechanisms by which specific cells and tissues respond differentially to hypoxia and how these different cellular responses are integrated to control animal physiology and behavior; (6) the roles of cytochrome P450 oxidases in transducing aspects of the hypoxia response; and (7) the interaction between the HIF-1 hypoxia-response pathway and the NMD (nonsense-mediated decay) pathway for RNA surveillance.