My laboratory studies fundamental mechanisms of odor recognition and olfactory behavior. The following projects are currently ongoing in my laboratory:

(1) In collaboration with Dr. Trudy Mackay we are investigating how the coordinated expression of ensembles of genes shapes behavior, using odor-guided behavior in Drosophila melanogaster as a model system. Using P-element insertional mutagenesis in an isogenic strain we can identify loci that participate in shaping olfactory behavior. These "smell-impaired (smi)" genes are then characterized at the molecular level and reduction in their expression products can be correlated quantitatively with impairment in odor- guided behavior.

(2) Among most mammals social interactions, such as courtship, mating, and aggression, are influenced by conspecific chemical cues (pheromones) that trigger stereotypic instinctive behaviors via the vomeronasal organ, the chemoreceptive organ of the accessory olfactory system. The long-term goal of this proposed research program is to increase our understanding of the nature and diversity of mammalian pheromones, the molecular mechanisms by which they activate chemosensory neurons in the vomeronasal organ, and the way in which the vomeronasal neural projection encodes messages that trigger distinct stereotyped behaviors in conspecific recipients. The role of pheromones in speciation is also of interest.

(3) In collaboration with Dr. Vandenbergh we are investigating the functions of axonal G-proteins in the vertebrate olfactory system. Whereas the role of G-proteins in the chemosensory transduction at the specialized dendritic endings of olfactory neurons has been investigated extensively, virtually no information is available about possible involvement of axonal G-proteins in signal transduction during the formation and maintenance of chemotopic projections. Previous studies revealed differential expression patterns of G_i2and G₀on axons of primary chemosensory neurons converging on distinct glomeruli in both the main and accessory olfactory bulb.We are using mice in which the gene for the a subunit of G₀ has been deleted via homologous recombination to determine whether deletion of the a subunit of  G₀ alters the functional organization of the olfactory projection.

(4) We are pursuing studies on the function and diversity of a new gene family, of which we discovered the first member, olfactomedin. Originally discovered as the major structural constituent of the lower mucus layer that coats the olfactory neuroepithelium, olfactomedin homologues have now been discovered throughout the mammalian brain and in many species, including invertebrates, such as Caenorhabditis elegans. The recent discovery that the trabecular meshwork inducible glucocorticoid response gene (TIGR), a protein closely associated with glaucoma, one of the leading causes of blindness, is a member of the olfactomedin family, is likely to generate considerable interest in this new gene family. Our recent work on olfactomedin involves extensive genomic analysis to identify highly divergent members of a gene family of human olfactomedin related problemswith distinct expression patterns.This new family of extracellular matrix proteins may in future studies become implicated in a variety of human diseases.