Michael J. Jurynec, PhD
- Mouse Genetics
- Joint Diseases
- Bone Diseases
- Variation (Genetics)
- Inflammation Mediators
- Disease Models, Animal
- Departments: Orthopaedics - Research Assistant Professor
Academic Office Information
George and Dolores Eccles Institute of Human Genetics
15 N 2030 E, Room: 5160
Salt Lake City, UT 84112
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.
|Other Training||University of Utah
Human Genetics and Developmental Biology
|Postdoctoral Fellowship||University of Utah
|Doctoral Training||University of Utah
- 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.
- Hoshijima K, Jurynec MJ, Grunwald DJ (2016). Precise genome editing by homologous recombination. Methods Cell Biol, 135, 121-47.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Hutson LD, Jurynec MJ, Yeo SY, Okamoto H, Chien CB (2003). Two divergent slit1 genes in zebrafish. Dev Dyn, 228(3), 358-69.
- 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.
- 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.
- 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.