Research Interests
Musculoskeletal Development and Homeostasis
The Gray laboratory pursues research on fundamental questions of vertebrate musculoskeletal developmental and homeostasis. We combine mouse and zebrafish genetics with cell, molecular, and systems biology approaches to determine the molecular genetics of how the elements of the spine undergo developmental morphogenesis in the embryo and during adolescent growth and how these same tissues are maintained in the adult. The lab has three main research programs:
1) Spine Development and Scoliosis
We pursue mouse and zebrafish genetic-based projects focused on understanding the contributions of 1) regulators of cartilaginous and soft connective tissues of the spine and 2) Adgrg6/cAMP/CREB signaling to spine development and disorders such as scoliosis and intervertebral disc degeneration. These projects characterize cellular and molecular origins of common musculoskeletal pathologies observed in humans, using a variety of genetic models which we have developed. From this work thus far, we determine origins and progression of idiopathic scoliosis that affect 3-4% of the pediatric population worldwide. We also established a new regulator of endochondral ossification and of early onset idiopathic scoliosis through our work on Prmt5 in collaboration with Steve Vokes.
2) Osteoarthritis and Disc Degeneration
In collaboration with Dr. Zhaoyang Liu, we use mouse as a model to determine roles of cartilage regulation and epigenetic regulators during the pathogenesis of osteoarthritis. We intend to determine the role of the G-protein coupled receptor Adgrg6 signaling in articular cartilage and intervertebral disc development and homeostasis. As an example, we showed how Adgrg6 is responsible for maintain anabolic factors in these tissues, while at the same time inhibiting catabolic and pro-inflammatory factors. We discover that this is in part due to the cAMP/CREB activating function of Adgrg6 which we seek to test as a disease modifying therapeutic for spine disorders and osteoarthritis. We are pursuing how additional pathways are integrated into this signaling pathway and how the signals cooperate with chromatin regulators such as Protein Methyltransferases and chondrogenic transcription factor to maintain homeostatic gene expression programs that promote healthy musculoskeletal tissues.
3) The Central Canal and Reissner Fiber and Spine Morphogenesis
Our work in zebrafish has established over 30 essential loci for spine development from which we have identified the crucial role of ependymal cell cilia and the Reissner fiber in the central spinal canal as regulators of spine morphogenesis. Additional spine development and scoliosis projects are studying mechanisms of upstream and downstream of the Reissner fiber to better understand how this structure is instructive for spine morphogenesis and homeostasis in the juvenile zebrafish model and whether this signaling is essential in mouse.
Musculoskeletal Development and Homeostasis
The Gray laboratory pursues research on fundamental questions of vertebrate musculoskeletal developmental and homeostasis. We combine mouse and zebrafish genetics with cell, molecular, and systems biology approaches to determine the molecular genetics of how the elements of the spine undergo developmental morphogenesis in the embryo and during adolescent growth and how these same tissues are maintained in the adult. The lab has three main research programs:
1) Spine Development and Scoliosis
We pursue mouse and zebrafish genetic-based projects focused on understanding the contributions of 1) regulators of cartilaginous and soft connective tissues of the spine and 2) Adgrg6/cAMP/CREB signaling to spine development and disorders such as scoliosis and intervertebral disc degeneration. These projects characterize cellular and molecular origins of common musculoskeletal pathologies observed in humans, using a variety of genetic models which we have developed. From this work thus far, we determine origins and progression of idiopathic scoliosis that affect 3-4% of the pediatric population worldwide. We also established a new regulator of endochondral ossification and of early onset idiopathic scoliosis through our work on Prmt5 in collaboration with Steve Vokes.
2) Osteoarthritis and Disc Degeneration
In collaboration with Dr. Zhaoyang Liu, we use mouse as a model to determine roles of cartilage regulation and epigenetic regulators during the pathogenesis of osteoarthritis. We intend to determine the role of the G-protein coupled receptor Adgrg6 signaling in articular cartilage and intervertebral disc development and homeostasis. As an example, we showed how Adgrg6 is responsible for maintain anabolic factors in these tissues, while at the same time inhibiting catabolic and pro-inflammatory factors. We discover that this is in part due to the cAMP/CREB activating function of Adgrg6 which we seek to test as a disease modifying therapeutic for spine disorders and osteoarthritis. We are pursuing how additional pathways are integrated into this signaling pathway and how the signals cooperate with chromatin regulators such as Protein Methyltransferases and chondrogenic transcription factor to maintain homeostatic gene expression programs that promote healthy musculoskeletal tissues.
3) The Central Canal and Reissner Fiber and Spine Morphogenesis
Our work in zebrafish has established over 30 essential loci for spine development from which we have identified the crucial role of ependymal cell cilia and the Reissner fiber in the central spinal canal as regulators of spine morphogenesis. Additional spine development and scoliosis projects are studying mechanisms of upstream and downstream of the Reissner fiber to better understand how this structure is instructive for spine morphogenesis and homeostasis in the juvenile zebrafish model and whether this signaling is essential in mouse.