My research program has two areas of emphasis:
Growth and development focusing on the skeleton in driving the relationship between skeletal size and body composition and
The genetic basis for health disorders and other traits 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 systemic hormones (e.g, growth hormone) and their downstream effectors such as insulin-like growth factor -I (IGF-I) along with local effectors such as vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGFs). An additional aspect that is critical to various animal industries is bone turnover and bone strength and the controlling mechanisms. The strategy used to characterize bone growth mechanisms involves different models. We are looking at heritability of bone quality in dairy cattle and sheep as well as in laboratory animals. We also use an in vitro system to 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. It also permits knockdown approaches to evaluate the impact of individual gene products. Another 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.
The second area of research emphasis in my laboratory focuses on characterizing the inheritance of health disorders and other traits 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 and traits are indeed heritable, and if so, what is the predicted mode of inheritance. Once a genetic basis to a disorder is confirmed, a concerted search for the molecular defect associated with that disorder or trait 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 West Highland White Terriers. Visit our web site for dog diseases under study: http://cgap.ucdavis.edu