Research

1. Growth and development focusing on the relationship between skeletal size and overall body composition and 
2. The genetic basis for health disorders in dogs.

My approach to the study of skeletal and body growth is one of vertical integration going from the whole animal to the molecular events controlling the observed phenotype. This work, both collaborative and independent, centers on the effects of growth hormone (GH), its direct consequences, and its downstream effectors such as insulin-like growth factor -I (IGF-I). The strategy used to characterize bone growth mechanisms involves several distinct models. The first model is the culture of growth plate primary explants which have been dissociated and cultured as relatively pure populations of chondrocytes which represent the different growth plate zones. We have fully developed this model in order to generate a reproducible system that retains the chondrocytic positional phenotype that is essential for further studies of growth plate response. This cell culture model allows for the identification of genes that may be responsible for the transition of cells from one zonal phenotype to another as well as assessing the effects of various growth promotants. A second model centers on analyzing GH-transgenic mice brought to this campus by Dr. J.D. Murray (Animal Science) from CSIRO in Australia. The GH transgenic mouse model has allowed us to study the effects of elevated GH on overall body growth, growth plate alterations and adipocyte proliferation and differentiation. To study bone turnover Kristin Evans is studying the inhibition of osteoclast function and the role of VEGF in growth plate action. Lauren Sheppard is also studying osteoclast function and bone remodeling as a consequence of bisphosphonate treatment. Finally, Logan Smith is characterizing a genetic bone defect prevalent in the sheep industry using specifically bred sheep.

The second area of research emphasis in my laboratory focuses on characterizing the inheritance of health disorders in the dog. This work, done with the essential collaboration of Dr. Thomas R. Famula of the UC Davis Animal Science Department, has first concentrated on demonstrating whether particular disorders are indeed heritable, and if so, what is the mode of inheritance. Once a genetic basis to a disorder is confirmed, pedigree data are evaluated as to the likelihood that a concerted search for a molecular marker linked to that disorder can be identified. This approach has been applied to deafness in Dalmatians, epilepsy in the Belgian Shepherd, English Mastiff, Giant Schnauzer, and Poodle, and Addison's disease in Bearded Collies, Leonbergers, Portuguese Water Dogs, Standard Poodles, and Westhighland White Terriers. This work is being undertaken by Janelle Belanger, Debbie Grossman, and Kristin Simpson.