Prof. David Karasik
We are especially interested in osteoporotic fractures of the hip and spine, which affect mostly older men and postmenopausal women; the lifetime risk for osteoporosis-related morbidity is higher than a woman’s combined risk for breast cancer, endometrial cancer and ovarian cancer. Fractures, as many other common diseases of aging, represent a genetically complex (controlled by multiple genes and also environment-dependent) disease. Genetic epidemiology therefore provides tools to decipher contribution of genetic factors and provide ways of using this knowledge for treating disease. Thus, genome-wide association studies (GWAS) became state-of-the-art technique for the new gene discovery. Genome-wide association approach offers the best chance of identifying novel biochemical/molecular mechanisms underlying fracture risk. We already have generated very exciting results by this approach: with the largest sample size so far on BMD, bone geometry, and muscle mass traits, more than 80 genome-wide significant loci have been identified; some of these genes are contributing to fractures. To note, focusing on shared genetic regulation of both bone and muscle by means of quantitative genetic analyses is a novel approach that is achievable with our sample and collaborations. The currently approved therapies for the prevention and treatment of osteoporosis are universally “bone-centric,” ignoring the important contribution of muscle to the maintenance of the strength of the skeleton. Our search for biological connections between the muscles and bones is aimed to inform novel molecular strategies of treatment and prevention of osteoporotic fractures and other devastating diseases of musculoskeleton.
Research using model organisms for functional validation of the genetic associations : In addition for a requirement for a human genetic association to be reproducible (replicated in an independent human sample), statistically-only identified associations are considered hypothetical unless validated in vitro or in vivo. Furthermore, the ultimate goal of genetic discovery is to define the mechanisms that underlie the association. To this extent, we perform targeted functional studies using the molecular biology techniques, once an allelic association for a gene of interest has been identified and replicated. Both the muscle and the bone phenotypes in animal models we are working with, will be characterized by sophisticated techniques.
Our continuous efforts are dedicated to the translational research, aimed to build a much needed bridge of communication between research scientists and physicians that will lead to novel treatments and prevention strategies. We therefore conduct research in genetic causes of common diseases with the affiliated hospitals. Recently, we entered into a collaboration with Dr Hussein Osamah, MD, of the ZivMedical Center, on a project named “Identification of the genetic components which are involved in the metabolic syndrome”.