Research Interests
Musculoskeletal Development and Homeostasis
Our research laboratory is dedicated to elucidating the critical processes that underpin the development and maintenance of the vertebral column, or spine. Utilizing state-of-the-art genomic and genome editing techniques, we explore these processes in both mouse and zebrafish model systems to uncover the molecular genetics associated with spinal disorders in humans. Our approach integrates a variety of methodologies, including i) the use of animal models and cell culture, ii) advanced imaging techniques, and other 'omics data, to deepen our understanding of the molecular genetics and pathogenesis of spine disorders. We have successfully established mouse and zebrafish models representing various musculoskeletal and spinal disorders, with relevance to human idiopathic or neuromuscular scoliosis. Through our research, we have identified crucial roles for signaling factors that regulate the homeostasis of dense cartilaginous tissues, which serve as significant contributors to idiopathic scoliosis. Additionally, we have discovered novel functions of motile cilia in the spinal canal and the Reissner fiber in the context of neuromuscular scoliosis development. In our commitment to advancing the global scientific community, we have developed innovative transgenic tools, including precision-edited genetic mutations, fluorescently tagged protein alleles, and enhancer-reporter lines that label specific cellular and tissue structures resources that have been actively requested and distributed worldwide. Moving forward, we will maintain our multi-tiered approach by combining zebrafish, mouse, and cell culture models, while drawing insights from human genomic studies. Our goal is to enhance the early diagnosis of pediatric and musculoskeletal diseases and to establish foundational knowledge of the genes and pathways involved in spine homeostasis.
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
Our research laboratory is dedicated to elucidating the critical processes that underpin the development and maintenance of the vertebral column, or spine. Utilizing state-of-the-art genomic and genome editing techniques, we explore these processes in both mouse and zebrafish model systems to uncover the molecular genetics associated with spinal disorders in humans. Our approach integrates a variety of methodologies, including i) the use of animal models and cell culture, ii) advanced imaging techniques, and other 'omics data, to deepen our understanding of the molecular genetics and pathogenesis of spine disorders. We have successfully established mouse and zebrafish models representing various musculoskeletal and spinal disorders, with relevance to human idiopathic or neuromuscular scoliosis. Through our research, we have identified crucial roles for signaling factors that regulate the homeostasis of dense cartilaginous tissues, which serve as significant contributors to idiopathic scoliosis. Additionally, we have discovered novel functions of motile cilia in the spinal canal and the Reissner fiber in the context of neuromuscular scoliosis development. In our commitment to advancing the global scientific community, we have developed innovative transgenic tools, including precision-edited genetic mutations, fluorescently tagged protein alleles, and enhancer-reporter lines that label specific cellular and tissue structures resources that have been actively requested and distributed worldwide. Moving forward, we will maintain our multi-tiered approach by combining zebrafish, mouse, and cell culture models, while drawing insights from human genomic studies. Our goal is to enhance the early diagnosis of pediatric and musculoskeletal diseases and to establish foundational knowledge of the genes and pathways involved in spine homeostasis.
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.