David Jonah Grunwald, Ph.D.

Our research is aimed at uncovering mechanisms that regulate the generation, organization, and maintenance of tissues in the vertebrate. Toward this end, we conduct genetic analyses of wildtype development and disease states in zebrafish, mice, and humans. One theme in the lab is to understand the molecular and genetic pathways that regulate the maintenance and differentiation of stem cells. Our studies have led us to the hypothesis that promoter proximal transcription pausing is needed to maintain multipotent precursor cells and that regulation of pause release is key to governance of the differentiation of stem cells. A second theme is how the regulation of intracellular calcium mobilization is used to pattern tissue development. A third theme is the optimization of genome modification strategies in the zebrafish to advance studies of gene function. Finally, we are interested in identifying pathways that are essential for maintaining homeostasis of the joint and whose perturbation underlies osteoarthritis.

Jurynec MJ, Gavile CM, Honeggar M, Ma Y, Veerabhadraiah SR, Novak KA, Hoshijima K, Kazmers NH, Grunwald DJ. (2022). The NOD/RIPK2 signaling pathway contributes to osteoarthritis susceptibility. Annals of the Rheumatic Diseases 2022 Oct;81(10):1465-1473. PMID: 35732460

Arveseth CD, Happ JT, Hedeen DS, Zhu JF, Capener JL, Klatt Shaw D, Deshpande I, Liang J, Xu J, Stubben SL, Nelson IB, Walker MF, Kawakami K, Inoue A, Krogan NJ, Grunwald DJ, Huttenhain R, Manglik A, Myers BR. (2021). Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits. PLoS Biol 19, e3001191.

Wike CL, Guo Y, Tan M, Nakamura R, Klatt Shaw D, Diaz N, Whittaker-Tademy AF, Durand NC, Lieberman Aiden E, Vaquerizas JM, Grunwald D, Takeda H, Cairns BR (2021). Chromatin architecture transitions from zebrafish sperm through early embryogenesis. Genome Res. 31, 981-994.

Jurynec MJ, Bai X, Bisgrove BW, Jackson H, Nechiporuk A, Palu RAS, Grunwald HA, Su YC, Hoshijima K, Yost HJ, Zon LI, Grunwald DJ. The Paf1 complex and P-TEFb have reciprocal and antagonist roles in maintaining multipotent neural crest progenitors. Development. 2019 Dec 16;146(24):dev180133. PMCID: PMC6955205 (Selected as a “Research Highlight”)

Hoshijima K, Jurynec MJ, Klatt Shaw D, Jacobi AM, Behlke MA, Grunwald DJ. Highly Efficient CRISPR-Cas9-Based Methods for Generating Deletion Mutations and F0 Embryos that Lack Gene Function in Zebrafish. Dev Cell. 2019 Dec 2;51(5):645-657.e4. PMCID: PMC6891219

Chagovetz AA, Klatt Shaw D, Ritchie E, Hoshijima K, Grunwald DJ. Interactions among ryanodine receptor isotypes contribute to muscle fiber type development and function. Dis Model Mech. 2019 Sep 18;13(2). PMCID: PMC6906632 (“Editor’s Choice” article)

Klatt Shaw D, Gunther D, Jurynec MJ, Chagovetz AA, Ritchie E, Grunwald DJ. Intracellular Calcium Mobilization is Required for Sonic Hedgehog Signaling. Dev Cell. 2018 May 21;45(4):512-525.e5. PMCID: PMC6007892 (F1000 Prime recommended)

Jurynec MJ, Sawitzke AD, Beals TC, Redd MJ, Stevens J, Otterud B, Leppert MH, Grunwald DJ. A hyperactivating proinflammatory RIPK2 allele associated with early-onset osteoarthritis. Hum Mol Genet. 2018 Jul 1;27(13):2383-2391. PMCID: PMC6620756 

Hoshijima K, Jurynec MJ, Grunwald DJ. Precise Editing of the Zebrafish Genome Made Simple and Efficient. Dev Cell. 2016 Mar 21;36(6):654-67. PMCID: PMC4806538