The primary objective of our research is to understand the function and pathology of complex physiological systems and metabolic processes. Our research focuses on identifying genes involved in the genetic variation of complex traits, mostly associated with musculoskeletal aging.
Osteoporotic fractures of the hip and spine are significant and prevalent health problems. Loss of muscle is an essential step in the osteoporotic fracture pathway, muscles transmit loads directly onto bones and contribute to stability and the risk of falling. The current therapies for the prevention and treatment of osteoporosis are universally “bone-centric,” ignoring the important contribution of muscle to maintaining skeletal strength. Our search for biological connections between the muscles and bones is aimed to inspire novel molecular strategies for the treatment and prevention of osteoporotic fractures and other devastating musculoskeletal diseases.
The ultimate goal of genetic discovery is to define mechanisms that underlie an observed association. Toward this aim, we perform targeted functional experiments, using molecular biology techniques, once an allelic association for a gene that has been identified – using bioinformatic approaches – and replicated in other human cohorts. We utilize the zebrafish (Danio rerio, ZF) as a valuable model for the human’s physiology and disease. The ZF is ideal for evaluating multiple organs simultaneously in vivo. The genomic organization, the genetic pathways controlling signal transduction, and the developmental pattern are largely conserved between ZF and mammals. The ZF is highly amenable to both molecular analysis and genetic manipulation, which allows establishing high-throughput screening platforms. ZF is a well-established model for embryogenesis and musculoskeletal development, especially for studying complex interactions between genes and the environment on both the development/growth and adult morphology and function.
We apply a CRISPR/Cas9 mediated genome editing, usually producing knockout models of fish genes, and establish genetically modified zebrafish lines. Muscle, adipose and bone phenotypes in animal models we are working with are characterized by sophisticated techniques. These include histological and fluorescent staining, transgenics, as well as microCT.
Our continuous efforts are dedicated to translational research that is aimed to fill the communication gap between research scientists and physicians. We hope to support the development of novel treatments and prevention strategies for of fracture, disability and frailty. This knowledge of pleiotropic relationships and cross-talk between muscles, bones, and fat, has a clinical value in advanced diagnostic measures of future risk of fracture and related diseases.
Updated: July 2021
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