Research Statement
My group works to discover and understand the functions of genes underlying the onset and progression of osteoarthritis. We use a combination of approaches including human genetics, bioinformatics, and model organisms (zebrafish and mouse) to elucidate the molecular and biological mechanisms that lead to changes in the synovial joint and contribute to the osteoarthritis phenotype.
Osteoarthritis (OA) is a common debilitating disease involving abnormal remodeling of joint tissues, severely reducing quality of life as a consequence of joint pain and limited mobility. It is the major cause of disability among adults. No cure for OA exists, and with the exception of surgical intervention, therapies tend to be solely palliative, failing to prevent the initiation or progression of the disease. Lack of basic scientific understanding of the genes and biological processes underlying or conferring susceptibility to OA is a key limitation to the development of effective therapies.
Analysis of families with highly penetrant, often severe, forms of osteoarthritis is a powerful approach for finding disease-causing variants. Deciphering how a human disease-associated variant affects gene function and leads to the disease state is a limiting step in understanding the genotype-phenotype correlation. Our recent work highlights the importance of combining human genetics with functional analyses in models. We identified gene variants associated with an inherited severe early-onset form of osteoarthritis. Analysis of the action of the gene in zebrafish embryos revealed the variant to be an activating mutation affecting the inflammation response pathway. These studies highlight inflammatory pathways as potentially important mechanisms driving the pathogenesis of osteoarthritis. Current work is aimed at testing whether the inflammation gene variant is sufficient to confer susceptibility to OA in mice and expanding the family studies to identify new gene variants and biological pathways that have strong effects on the pathogenesis of this disease.
Education History
| Postdoctoral Fellowship |
University of Utah |
Postdoctoral Fellow |
|---|---|---|
|
University of Utah |
PhD | |
| Undergraduate |
Emory University |
BS |
Selected Publications
Journal Article
- Jurynec MJ, Gavile CM, Honeggar M, Ma Y, Veerabhadraiah SR, Novak KA, Hoshijima K, Kazmers NH, Grunwald DJ (2022). NOD/RIPK2 signalling pathway contributes to osteoarthritis susceptibility. Ann Rheum Dis, 81(10), 1465-1473. (Read full article)
- Gavile CM, Kazmers NH, Novak KA, Meeks HD, Yu Z, Thomas JL, Hansen C, Barker T, Jurynec MJ (2022). Familial Clustering and Genetic Analysis of Severe Thumb Carpometacarpal Joint Osteoarthritis in a Large Statewide Cohort. J Hand Surg Am, 47(10), 923-933. (Read full article)
- Miller M, Kazmers NH, Chalmers PN, Tashjian RZ, Jurynec MJ (2021). Supraspinatus Rotator Cuff Repair: A Mouse Model and Technique. Arthrosc Tech, 10(8), e1949-e1954. (Read full article)
- Teerlink CC, Jurynec MJ, Hernandez R, Stevens J, Hughes DC, Brunker CP, Rowe K, Grunwald DJ, Facelli JC, Cannon-Albright LA (2020). A role for the MEGF6 gene in predisposition to osteoporosis. Ann Hum Genet, 85(2), 58-72. (Read full article)
- Kazmers NH, Meeks HD, Novak KA, Yu Z, Fulde GL, Thomas JL, Barker T, Jurynec MJ (2020). Familial clustering of erosive hand osteoarthritis in a large statewide cohort. Arthritis Rheumatol, 73(3), 440-447. (Read full article)
- Santoriello C, Sporrij A, Yang S, Flynn RA, Henriques T, Dorjsuren B, Custo Greig E, McCall W, Stanhope ME, Fazio M, Superdock M, Lichtig A, Adatto I, Abraham BJ, Kalocsay M, Jurynec M, Zhou Y, Adelman K, Calo E, Zon LI (2020). RNA helicase DDX21 mediates nucleotide stress responses in neural crest and melanoma cells. Nat Cell Biol, 22(4), 372-379. (Read full article)
- Kazmers NH, Yu Z, Barker T, Abraham T, Romero R, Jurynec MJ (2019). Evaluation for Kienböck Disease Familial Clustering: A Population-Based Cohort Study. J Hand Surg Am, 45(1), 1-8.e1. (Read full article)
- Jurynec MJ, Bai X, Bisgrove BW, Jackson H, Nechiporuk A, Palu RAS, Grunwald HA, Su YC, Hoshijima K, Yost HJ, Zon LI, Grunwald DJ (2019). The Paf1 complex and P-TEFb have reciprocal and antagonist roles in maintaining multipotent neural crest progenitors. Development, 146(24). (Read full article)
- Hoshijima K, Jurynec MJ, Klatt Shaw D, Jacobi AM, Behlke MA, Grunwald DJ (2019). Highly Efficient CRISPR-Cas9-Based Methods for Generating Deletion Mutations and F0 Embryos that Lack Gene Function in Zebrafish. Dev Cell, 51(5), 645-657.e4. (Read full article)
- Jurynec MJ, Sawitzke AD, Beals TC, Redd MJ, Stevens J, Otterud B, Leppert MF, Grunwald DJ (2018). A hyperactivating proinflammatory RIPK2 allele associated with early-onset osteoarthritis. Hum Mol Genet, 27(13), 2383-2391. (Read full article)
- Jurynec MJ, Sawitzke AD, Beals TC, Redd MJ, Stevens J, Otterud B, Leppert MF, Grunwald DJ (2018). A hyperactivating proinflammatory RIPK2 allele associated with early-onset osteoarthritis. Hum Mol Genet, 27(13), 2406. (Read full article)
- Klatt Shaw D, Gunther D, Jurynec MJ, Chagovetz AA, Ritchie E, Grunwald DJ (2018). Intracellular Calcium Mobilization Is Required for Sonic Hedgehog Signaling. Dev Cell, 45(4), 512-525.e5. (Read full article)
- Klatt Shaw D, Gunther D, Jurynec MJ, Chagovetz AA, Ritchie E, Grunwald DJ (10 May 2018). Intracellular Calcium Mobilization Is Required for Sonic Hedgehog Signaling. Dev Cell.
- Jurynec MJ, Sawitzke AD, Beals TC, Redd MJ, Stevens J, Otterud B, Leppert MH, Grunwald DJ (04/16/2018). A hyperactivating proinflammatory RIPK2 allele associated with early-onset osteoarthritis. Hum Mol Genet.
- Hoshijima K, Jurynec MJ, Grunwald DJ (2016). Precise Editing of the Zebrafish Genome Made Simple and Efficient. Dev Cell, 36(6), 654-67. (Read full article)
- Hoshijima K, Jurynec MJ, Grunwald DJ (2016). Precise genome editing by homologous recombination. Methods Cell Biol, 135, 121-47. (Read full article)
- Dahlem TJ, Hoshijima K, Jurynec MJ, Gunther D, Starker CG, Locke AS, Weis AM, Voytas DF, Grunwald DJ (2012). Simple methods for generating and detecting locus-specific mutations induced with TALENs in the zebrafish genome. PLoS Genet, 8(8), e1002861. (Read full article)
- Wythe JD, Jurynec MJ, Urness LD, Jones CA, Sabeh MK, Werdich AA, Sato M, Yost HJ, Grunwald DJ, Macrae CA, Li DY (2011). Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish. Dis Model Mech, 4(5), 607-21. (Read full article)
- Jurynec MJ, Grunwald DJ (2010). SHIP2, a factor associated with diet-induced obesity and insulin sensitivity, attenuates FGF signaling in vivo. Dis Model Mech, 3(11-12), 733-42. (Read full article)
- Bai X, Kim J, Yang Z, Jurynec MJ, Akie TE, Lee J, LeBlanc J, Sessa A, Jiang H, DiBiase A, Zhou Y, Grunwald DJ, Lin S, Cantor AB, Orkin SH, Zon LI (2010). TIF1gamma controls erythroid cell fate by regulating transcription elongation. Cell, 142(1), 133-43. (Read full article)
- Jurynec MJ, Xia R, Mackrill JJ, Gunther D, Crawford T, Flanigan KM, Abramson JJ, Howard MT, Grunwald DJ (2008). Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle. Proc Natl Acad Sci U S A, 105(34), 12485-90. (Read full article)
- Lamason RL, Mohideen MA, Mest JR, Wong AC, Norton HL, Aros MC, Jurynec MJ, Mao X, Humphreville VR, Humbert JE, Sinha S, Moore JL, Jagadeeswaran P, Zhao W, Ning G, Makalowska I, McKeigue PM, Odonnell D, Kittles R, Parra EJ, Mangini NJ, Grunwald DJ, Shriver MD, Canfield VA, Cheng KC (2005). SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science, 310(5755), 1782-6. (Read full article)
- Hutson LD, Jurynec MJ, Yeo SY, Okamoto H, Chien CB (2003). Two divergent slit1 genes in zebrafish. Dev Dyn, 228(3), 358-69. (Read full article)
- Buck CR, Jurynec MJ, Gupta DK, Law AK, Bilger J, Wallace DC, McKeon RJ (2003). Increased adenine nucleotide translocator 1 in reactive astrocytes facilitates glutamate transport. Exp Neurol, 181(2), 149-58. (Read full article)
- Jurynec MJ, Riley CP, Gupta DK, Nguyen TD, McKeon RJ, Buck CR (2003). TIGR is upregulated in the chronic glial scar in response to central nervous system injury and inhibits neurite outgrowth. Mol Cell Neurosci, 23(1), 69-80. (Read full article)
- McKeon RJ, Jurynec MJ, Buck CR (1999). The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. J Neurosci, 19(24), 10778-88. (Read full article)
Review
- Davies M, Jurynec MJ, Gomez-Alvarado F, Hu D, Feeley SE, Allen-Brady K, Tashjian RZ, Feeley BT (2022). Current cellular and molecular biology techniques for the orthopedic surgeon-scientist. [Review]. J Shoulder Elbow Surg, 32(1), e11-e22. (Read full article)
- Kim JS, Amendola A, Barg A, Baumhauer J, Brodsky JW, Cushman DM, Gonzalez TA, Janisse D, Jurynec MJ, Lawrence Marsh J, Sofka CM, Clanton TO, Anderson DD (2022). Summary Report of the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society's Symposium on Targets for Osteoarthritis Research: Part 1: Epidemiology, Pathophysiology, and Current Imaging Approaches. [Review]. Foot Ankle Orthop, 7(4), 24730114221127011. (Read full article)
- Kim JS, Amendola A, Barg A, Baumhauer J, Brodsky JW, Cushman DM, Gonzalez TA, Janisse D, Jurynec MJ, Lawrence Marsh J, Sofka CM, Clanton TO, Anderson DD (2022). Summary Report of the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society's Symposium on Targets for Osteoarthritis Research: Part 2: Treatment Options. [Review]. Foot Ankle Orthop, 7(4), 24730114221127013. (Read full article)
Other
- Tashjian RZ, Kazmers NH, Epperson RT, Honeggar M, Ma Y, Chalmers PN, Williams DL, Jurynec MJ (2021). The effect of estrogen-like compound on rotator cuff tendon healing in a murine model. J Orthop Res (39(12), pp. 2711-2724). United States. (Read full article)