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 two 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) The Central Canal Cilia dynamics, the 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. We recently generated a novel computer vision assisted ML approach for the automated detection , masking, and quantification of cilia morphology and dynamics which will allows us to deeply quantify cilia behaviors in vivo.
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 two 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) The Central Canal Cilia dynamics, the 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. We recently generated a novel computer vision assisted ML approach for the automated detection , masking, and quantification of cilia morphology and dynamics which will allows us to deeply quantify cilia behaviors in vivo.
