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Ryan S Gray
Assistant Professor, Assistant Professor of Pediatrics
Department of Nutritional Sciences, Department of PediatricsWe study the development cell biology and genetics regulating spine development and disorders.ryan.gray@austin.utexas.edu
Phone: 512-495-5052
Office Location
HLB
Postal Address
1400 BARBARA JORDAN BLVD
AUSTIN, TX 78723-
The goal of my lab is the study of the cellular and molecular mechanisms of spine development and homeostasis using primarily the mouse and zebrafish model systems. We choose to utilize both mouse and zebrafish models to provide complementary approaches to study musculoskeletal development and disease.
We developed conditional mouse models of (i) idiopathic scoliosis (IS) and intervertebral disc herniation by removing Gpr126/Adgrg6 function in osteochondral progenitors (Human Molecular Genetics, 2015 and PLoS Genetics, 2019); and (ii) early-onset scoliosis after conditional ablation of Prmt5 function in the same progenitor cell type (Dis Model Mech. 2019). Together these results promote a model of the essential role of cartilaginous tissues and extracellular matrix or ‘matriosome’ for the pathogenesis of idiopathic scoliosis (Bone Research, 2019).
We are at the forefront of establishing the zebrafish model system to analysis a variety of scoliosis pathologies including congenital malformations (Developmental Biology, 2014) and IS (Development Dynamics, 2014 and Developmental Biology 2020). In an effort to promote gene discovery, we established a forward genetic screen in zebrafish which isolated a novel collection of adult viable scoliosis mutants, which are the focus of ongoing studies. To assist in isolation of the causative mutations in this collection, we help develop robust methods for rapid mapping and variant identification using modern genome sequencing (G3, 2017). Thus far, our studies in zebrafish identified common mechanistic roles for scoliosis and hydrocephalus affecting alterations in the physiology of the cerebrospinal fluid (PLOS Genetics, 2018) and established a novel, essential role for a cerebrospinal canal resident protein component, the ‘Reissner fiber’, which regulates spine morphogenesis downstream of disrupted cerebrospinal fluid flow (Current Biology, 2020). We will continue to use a multi-tiered approach, combining zebrafish, mouse, and cell culture models, informed by human genomic studies, with the goal to inform the diagnosis of pediatric/musculoskeletal diseases and provide avenues for therapeutic interventions of these disorders in humans.
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Cell and Developmental Biology, and Genetics of spine development and disorders using Mouse and Zebrafish animal models.
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Most recent publications:
1: Gray RS, Gonzalez R, Ackerman SD, Minowa R, Griest JF, Bayrak MN, Troutwine B, Canter S, Monk KR, Sepich DS, Solnica-Krezel L. Postembryonic screen for mutations affecting spine development in zebrafish. Dev Biol. 2021 Mar;471:18-33. doi: 10.1016/j.ydbio.2020.11.009. Epub 2020 Dec 5. PMID: 33290818.
2: Wang Y, Liu Z, Yang G, Gao Q, Xiao L, Li J, Guo C, Troutwine BR, Gray RS, Xie L, Zhang H. Coding Variants Coupled With Rapid Modeling in Zebrafish Implicate Dynein Genes, dnaaf1 and zmynd10, as Adolescent Idiopathic Scoliosis Candidate Genes. Front Cell Dev Biol. 2020 Nov 4;8:582255. doi: 10.3389/fcell.2020.582255. PMID: 33251213; PMCID: PMC7672046.
3: Bagnat M, Gray RS. Development of a straight vertebrate body axis. Development. 2020 Oct 6;147(21):dev175794. doi: 10.1242/dev.175794. PMID: 33023886; PMCID: PMC7561478.
4: Troutwine BR, Gontarz P, Konjikusic MJ, Minowa R, Monstad-Rios A, Sepich DS, Kwon RY, Solnica-Krezel L, Gray RS. The Reissner Fiber Is Highly Dynamic In Vivo and Controls Morphogenesis of the Spine. Curr Biol. 2020 Jun 22;30(12):2353-2362.e3. doi: 10.1016/j.cub.2020.04.015. Epub 2020 May 7. PMID: 32386529.
5: Wise CA, Sepich D, Ushiki A, Khanshour AM, Kidane YH, Makki N, Gurnett CA, Gray RS, Rios JJ, Ahituv N, Solnica-Krezel L. The cartilage matrisome in adolescent idiopathic scoliosis. Bone Res. 2020 Mar 9;8:13. doi: 10.1038/s41413-020-0089-0. PMID: 32195011; PMCID: PMC7062733.
6: Liu Z, Ramachandran J, Vokes SA, Gray RS. Regulation of terminal hypertrophic chondrocyte differentiation in Prmt5mutant mice modeling infantile idiopathic scoliosis. Dis Model Mech. 2019 Dec 17;12(12):dmm041251. doi: 10.1242/dmm.041251. PMID: 31848143; PMCID: PMC6955203.
7: Busse B, Galloway JL, Gray RS, Harris MP, Kwon RY. Zebrafish: An Emerging Model for Orthopedic Research. J Orthop Res. 2020 May;38(5):925-936. doi: 10.1002/jor.24539. Epub 2019 Dec 12. PMID: 31773769; PMCID: PMC7162720.
8: Liu Z, Easson GWD, Zhao J, Makki N, Ahituv N, Hilton MJ, Tang SY, Gray RS. Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice. PLoS Genet. 2019 Oct 25;15(10):e1008096. doi: 10.1371/journal.pgen.1008096. PMID: 31652254; PMCID: PMC6834287.
9: Ramachandran J, Liu Z, Gray RS, Vokes SA. PRMT5 is necessary to form distinct cartilage identities in the knee and long bone. Dev Biol. 2019 Dec 15;456(2):154-163. doi: 10.1016/j.ydbio.2019.08.012. Epub 2019 Aug 20. PMID: 31442442; PMCID: PMC6884688.
10: Konjikusic MJ, Yeetong P, Boswell CW, Lee C, Roberson EC, Ittiwut R, SuphapeetiCENSORED K, Ciruna B, Gurnett CA, Wallingford JB, Shotelersuk V, Gray RS. Mutations in Kinesin family member 6 reveal specific role in ependymal cell ciliogenesis and human neurological development. PLoS Genet. 2018 Nov 26;14(11):e1007817. doi: 10.1371/journal.pgen.1007817. PMID: 30475797; PMCID: PMC6307780.
Please find my current biblography at Google Scholar
https://scholar.google.com/citations?user=I3qwoEEAAAAJ&hl=en
Complete List of Published Work in MyBibliography:
https://www.ncbi.nlm.nih.gov/myncbi/ryan.gray.1/bibliography/public/
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UT Austin CNS Catalyst Grant Program, Vokes and Gray, “PRMT5-dependent Regulation of Articular Cartilage Homeostasis and Osteoarthritis.”
2017 - ORS Spine Section Early Investigator Podium Award
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2020, Dell Children’s Pediatrics Research Seminar “Defining the Molecular Genetics and Pathogenesis of Idiopathic Scoliosis” - CME accredited.
2020, The Allied Genetics Conference 2020, “The Reissner Fiber is Highly Dynamic in vivo and Controls Morphogenesis of the Spine” Selected speaker (online meeting due to COVID).
2019, The Company of Biologists workshop on Understanding Human Birth Defects in the Genomic Age, West Sussex, UK, “Mediators of spine stability using the zebrafish model system: from fibers to flow”.
2019, University of North Carolina Orthopedics Department Seminar, Chapel Hill, NC, “The pathogenesis of idiopathic scoliosis: effectors of the intervertebral disc and endochondral ossification”.
2019, Duke University School of Medicine, Department of Orthopedics, Durham, NC, “The pathogenesis of idiopathic scoliosis: effectors of the intervertebral disc and endochondral ossification”.
2019, Syracuse University Biology Department Seminar Series Fall 2019, “Mediators of spine stability using the zebrafish model system: from fibers to flow”.
2019, University of Colorado Denver Orthopedics Mack Clayton Visiting Scientist Lecturer, “The Pathogenesis of Idiopathic Scoliosis: Effectors of the Intervertebral Disc and Endochondral Ossification”.
2019, The 14th International Zebrafish Conference, Suzhou, China, “Identification of genetic factors contributing to spine stability and ventricular homeostasis in zebrafish”.
2019, The Orthopedics Research Society 2019 Annual Meeting, Austin, TX, “Zebrafish as an Emerging Model for Orthopaedic Research Workshop: Discovering the mediators of spine stability using the zebrafish model system”.
2019, The Orthopedics Research Society 2019 Annual Meeting, Austin, TX, “PRMT5 Is a Novel Regulator for Spine Stability and Intervertebral Disc Homeostasis in Mouse”. Selected speaker.
2019, 8th Strategic Conference of Zebrafish Investigators – January 12-15, 2019 at the Asilomar Conference Grounds, Pacific Grove, Monterey, California, “Identification of genetic factors contributing to spine stability and ventricular homeostasis in zebrafish”. Selected speaker.
2018, 9th Adhesion GPRC Workshop, Portland, OR, “ADGRG6 is essential for homeostasis of the intervertebral disc in mouse”. Selected speaker.
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NTR126L
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