I am an investigator in a program project to study the cross-talk between bone and skeletal muscle directed by Dr. Lynda Bonewald, an expert on osteocyte cell biology. One of the projects in this program focuses on muscle factors that mediate the beneficial effects of exercise on the musculoskeletal system with the goal of developing therapeutics against aging-induced osteoporosis and sarcopenia. I helped to identify the metabolite b-aminoisobutyric acid (BAIBA) as an osteocyte viability factor and conducted in vivo unloading experiments showing that BAIBA prevents bone and skeletal muscle loss. These findings were published in Cell Reports. I also found that irisin, like BAIBA, is also an osteocyte survival under oxidative stress. These results were published in Cell as a collaboration with Dr. Bruce Spiegelman. Also, as a component of the program project, I have been working on a project studying the impact of long-term exercise from middle-age to advanced age on aging-induced musculoskeletal deterioration.
I received a Ralph W. and Grace M. Showalter Research Grant in 2017 to identify the molecular mechanisms responsible for the BAIBA effects on bone, specifically, signaling mechanisms responsible for osteocyte viability and energy metabolism using in vitro and in vivo models. I have optimized a technique for cell metabolic analysis of osteocytes using a Seahorse Analyzer to examine the effect of BAIBA. These studies have led to my independent research, where I have become interested in bone energy metabolism, especially osteocyte lipid metabolism under mechanical loading. I have substantial experience in performing in vitro mechanical loading experiments, isolating primary osteocytes from young and aged mice, and generating in vitro mechanical loading data as described in this application. I have generated a PPARd osteocyte conditional knockout mouse model with start-up funds and the related in vivo and in vitro preliminary data presented in the application.