ZFIN ID: ZDB-PERS-060829-5
Shavit, Jordan
Email: jshavit@umich.edu
URL: http://www.shavitlab.org
Affiliation: Shavit Lab
Address: Department of Pediatrics University of Michigan 8301 MSRB III 1500 E. Medical Center Drive Ann Arbor, MI 48109-5646 USA
Phone: 734-647-4365
Fax: 734-936-2888

Our interest is in “clinically directed basic research” in the field of blood coagulation disorders. We have been developing zebrafish models of human clotting diseases using targeted mutagenesis with zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and CRISPR/Cas (clustered regularly interspaced short palindromic repeats) endoribonuclease technology. Sensitized ENU mutagenesis and small molecule screens are currently being performed on zebrafish mutants to identify modifier loci.

Bando, H., Gergics, P., Bohnsack, B.L., Toolan, K.P., Richter, C.E., Shavit, J.A., Camper, S.A. (2020) otx2b mutant zebrafish have pituitary, eye and mandible defects that model mammalian disease. Human molecular genetics. 29(10):1648-1657
Grzegorski, S.J., Hu, Z., Liu, Y., Yu, X., Ferguson, A.C., Madarati, H., Friedmann, A.P., Reyon, D., Kim, P.Y., Kretz, C.A., Joung, J.K., Shavit, J.A. (2020) Disruption of the kringle 1 domain of prothrombin leads to late onset mortality in zebrafish. Scientific Reports. 10:4049
Weyand, A.C., Grzegorski, S.J., Rost, M.S., Lavik, K.I., Ferguson, A.C., Menegatti, M., Richter, C.E., Asselta, R., Duga, S., Peyvandi, F., Shavit, J.A. (2019) Analysis of factor V in zebrafish demonstrates minimal levels needed for early hemostasis. Blood advances. 3:1670-1680
Thiessen, K.D., Grzegorski, S.J., Chin, Y., Higuchi, L., Wilkinson, C.J., Shavit, J.A., Kramer, K.L. (2019) Zebrafish otolith biomineralization requires polyketide synthase. Mechanisms of Development. 157:1-9
Hortle, E., Johnson, K.E., Johansen, M.D., Nguyen, T., Shavit, J.A., Britton, W.J., Tobin, D.M., Oehlers, S.H. (2019) Thrombocyte inhibition restores protective immunity to mycobacterial infection in zebrafish. The Journal of infectious diseases. 220(3):524-534
Hu, Z., Lavik, K.I., Liu, Y., Vo, A.H., Richter, C.E., Di Paola, J., Shavit, J.A. (2019) Loss of fibrinogen in zebrafish results in an asymptomatic embryonic hemostatic defect and synthetic lethality with thrombocytopenia. Journal of thrombosis and haemostasis : JTH. 17(4):607-617
Maitra, D., Bragazzi Cunha, J., Elenbaas, J.S., Bonkovsky, H.L., Shavit, J.A., Omary, M.B. (2019) Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury. Cellular and molecular gastroenterology and hepatology. 8:535-548
Rost, M.S., Shestopalov, I., Liu, Y., Vo, A.H., Richter, C.E., Emly, S.M., Barrett, F.G., Stachura, D.L., Holinstat, M., Zon, L.I., Shavit, J.A. (2018) Nfe2 is dispensable for early but required for adult thrombocyte formation and function in zebrafish. Blood advances. 2:3418-3427
Khoriaty, R., Hesketh, G.G., Bernard, A., Weyand, A.C., Mellacheruvu, D., Zhu, G., Hoenerhoff, M.J., McGee, B., Everett, L., Adams, E.J., Zhang, B., Saunders, T.L., Nesvizhskii, A.I., Klionsky, D.J., Shavit, J.A., Gingras, A.C., Ginsburg, D. (2018) Functions of the COPII gene paralogs SEC23A and SEC23B are interchangeable in vivo. Proceedings of the National Academy of Sciences of the United States of America. 115(33):E7748-E7757
Hu, Z., Liu, Y., Huarng, M.C., Menegatti, M., Reyon, D., Rost, M.S., Norris, Z.G., Richter, C.E., Stapleton, A.N., Chi, N.C., Peyvandi, F., Joung, J.K., Shavit, J.A. (2017) Genome editing of factor X in zebrafish reveals unexpected tolerance of severe defects in the common pathway. Blood. 130(5):666-676
Williams, L.M., Lago, B.A., McArthur, A.G., Raphenya, A.R., Pray, N., Saleem, N., Salas, S., Paulson, K., Mangar, R.S., Liu, Y., Vo, A.H., Shavit, J.A. (2016) The transcription factor, Nuclear factor, erythroid 2 (Nfe2), is a regulator of the oxidative stress response during Danio rerio development. Aquatic toxicology (Amsterdam, Netherlands). 180:141-154
Kc, R., Srivastava, A., Wilkowski, J.M., Richter, C.E., Shavit, J.A., Burke, D.T., Bielas, S.L. (2016) Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation detection. Scientific Reports. 6:32048
Elenbaas, J.S., Maitra, D., Liu, Y., Lentz, S.I., Nelson, B., Hoenerhoff, M.J., Shavit, J.A., Omary, M.B. (2016) A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 30(5):1798-810
Rost, M.S., Grzegorski, S.J., Shavit, J.A. (2016) Quantitative methods for studying hemostasis in zebrafish larvae. Methods in cell biology. 134:377-89
Huarng, M.C., Shavit, J.A. (2015) Simple and Rapid Quantification of Thrombocytes in Zebrafish Larvae. Zebrafish. 12(3):238-42
Kretz, C.A., Weyand, A.C., Shavit, J.A. (2015) Modeling Disorders of Blood Coagulation in the Zebrafish. Current pathobiology reports. 3:155-161
Ghosh, A., Vo, A., Twiss, B.K., Kretz, C.A., Jozwiak, M.A., Montgomery, R.R., Shavit, J.A. (2015) Corrigendum to "Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage". Advances in hematology. 2015:526854
Weyand, A.C., Shavit, J.A. (2014) Zebrafish as a model system for the study of hemostasis and thrombosis. Current opinion in hematology. 21(5):418-22
Liu, Y., Kretz, C.A., Maeder, M.L., Richter, C.E., Tsao, P., Vo, A.H., Huarng, M.C., Rode, T., Hu, Z., Mehra, R., Olson, S.T., Joung, J.K., and Shavit, J.A. (2014) Targeted mutagenesis of zebrafish antithrombin III triggers disseminated intravascular coagulation and thrombosis, revealing insight into function. Blood. 124(1):142-50
Raeker, M.Ö., Shavit, J.A., Dowling, J.J., Michele, D.E., and Russell. M.W. (2014) Membrane-myofibril cross-talk in myofibrillogenesis and in muscular dystrophy pathogenesis: lessons from the zebrafish. Frontiers in Physiology. 5:14
Vo, A.H., Swaroop, A., Liu, Y., Norris, Z.G., and Shavit, J.A. (2013) Loss of fibrinogen in zebrafish results in symptoms consistent with human hypofibrinogenemia. PLoS One. 8(9):e74682
Ghosh, A., Vo, A., Twiss, B.K., Kretz, C.A., Jozwiak, M.A., Montgomery, R.R., and Shavit, J.A. (2012) Characterization of zebrafish von Willebrand factor reveals conservation of domain structure, multimerization, and intracellular storage. Advances in hematology. 2012:214209
Chen, X.W., Leto, D., Xiao, J., Goss, J., Wang, Q., Shavit, J.A., Xiong, T., Yu, G., Ginsburg, D., Toomre, D., Xu, Z., and Saltiel, A.R. (2011) Exocyst function regulated by effector phosphorylation. Nature cell biology. 13(5):580-588
Su, F., Juarez, M.A., Cooke, C.L., LaPointe, L., Shavit, J.A., Yamaoka, J.S., and Lyons, S.E. (2007) Differential Regulation of Primitive Myelopoiesis in the Zebrafish by Spi-1/Pu.1 and C/ebp1. Zebrafish. 4(3):187-199
Buchner, D.A., Su, F., Yamaoka, J.S., Kamei, M., Shavit, J.A., Barthel, L.K., McGee, B., Amigo, J.D., Kim, S., Hanosh, A.W., Jagadeeswaran, P., Goldman, D., Lawson, N.D., Raymond, P.A., Weinstein, B.M., Ginsburg, D., and Lyons, S.E. (2007) pak2a mutations cause cerebral hemorrhage in redhead zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 104(35):13996-140001

1. Shavit JA and Motto DG. Coagulation and metastasis; an unexpected role for von Willebrand factor. J Thromb Haemost 4:517-518, 2006.
2. Lemmerhirt HL, Shavit JA, Levy GG, Cole SM, Long JC, and Ginsburg D. Enhanced VWF biosynthesis and elevated plasma VWF due to a natural variant in the murine Vwf gene. Blood 108:3061-7, 2006.
3. Lemmerhirt HL, Broman KW, Shavit JA, and Ginsburg D. Genetic regulation of plasma von Willebrand factor levels: QTL analysis in a mouse model. J Thromb Haemost 5:329-335, 2007.
4. Shavit JA, Manichaikul A, Lemmerhirt HL, Broman KW, Ginsburg D. Modifiers of von Willebrand factor identified by natural variation in inbred strains of mice. Blood, 114:5368-74, 2009.
5. Peters LL, Shavit JA, Lambert AJ, Tsaih S, Li Q, Su Z, Leduc MS, Paigen B, Churchill, GA, Ginsburg D, and Brugnara C. Sequence variation at multiple loci influences red cell hemoglobin concentration. Blood, 116:e139-49, 2010.
6. Chen X, Leto D, Xiao J, Goss J, Wang Q, Shavit JA, Xiong T, Yu G, Ginsburg D, Toomre D, Xu Z, and Saltiel AR. The function of the exocyst is regulated by effector phosphorylation. Nat Cell Biol, 13:580-8, 2011.
7. Shavit JA. The bleeding edge of symptom assessment. Pediatr Blood Cancer, 58:657-8, 2012.
8. Desch KC, Ozel AB, Siemieniak D, Kalish Y, Shavit JA, Thornburg CD, Sharathkumar AA, McHugh CP, Laurie CC, Crenshaw A, Mirel DB, Kim Y, Cropp CD, Molloy AM, Kirke PN, Bailey-Wilson JE, Wilson AF, Mills JL, Scott JM, Brody LC, Li JZ, Ginsburg D. Linkage analysis identifies a novel locus for plasma von Willebrand factor undetected by genome-wide association. Proc Natl Acad Sci USA, 110:588-93, 2013.
9. Dang, LT, Shavit JA, Singh, RK, Joshi SM, Leber SM, Barks, JD, and Shellhaas RA. Subdural hemorrhages associated with antithrombotic therapy in infants with cerebral atrophy, Pediatrics, 134(3):e889-93, 2014.
10. Weyand AC, Lombel RM, Pipe SW, and Shavit JA. The role of platelets and ε-aminocaproic acid in arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome associated hemorrhage. Pediatr Blood Cancer, 63:561-3, 2016.
11. Hacker KE, Fahey CC, Shinsky SA, Chiang YJ, DiFiore JV, Jha DK, Vo AH, Shavit JA, Davis IJ, Strahl BD, Rathmell WK. Structure/function analysis of recurrent mutations in SETD2 reveals a critical and conserved role for a SET domain residue in maintaining protein stability and H3K36 trimethylation. J Biol Chem, 291:21283-95, 2016.
12. Weyand AC and Shavit JA. Agent specific effects of anticoagulant induced alopecia. Res Pract Thromb Haemost, 1:90-92, 2017.
13. Nielsen JB, Thorolfsdottir RB, Fritsche LG, Zhou W…(49 total authors)…Shavit JA…Stefansson K, Abecasis GR, Hveem K, and Willer CJ. Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. Nat Genet, 50:1234-9, 2018.
14. Weyand AC, Dorfman A, Shavit JA, and Pipe SW. Emicizumab prophylaxis to facilitate anticoagulation therapy for management of intra-atrial thrombosis in severe hemophilia with an inhibitor. Haemophilia, 25:e203-5, 2019.
15. Khoriaty R, Ozel AB, Ramdas S, Ross C, Desch K, Shavit JA, Everett L, Siemieniak D, Li JZ, Ginsburg D. Genome-wide linkage analysis and whole-exome sequencing identifies an ITGA2B mutation in a family with thrombocytopenia. Br J Haematol, 186:574-9, 2019.
16. Maitra D, Cunha JB, Elenbaas JS, Bonkovsky HL, Shavit JA, and Omary MB. Porphyrin-induced protein oxidation and aggregation as a mechanism of porphyria associated cell injury. Cell Mol Gastroenterol Hepatol, 8:535-48, 2019.
17. Weyand AC, Flood VH, Shavit JA, and Pipe SW. Efficacy of emicizumab in a pediatric patient with type 3 von Willebrand disease and alloantibodies. Blood Adv, 3:2748-50, 2019.
18. Helms AS, Tang VT, O’Leary TS, Friedline S, Wauchope M, Arora A, Wasserman AH, Smith ED, Lee LM, Wen X, Shavit JA, Liu AP, Previs MJ, and Day SM. Effects of MYBPC3 loss of function mutations preceding hypertrophic cardiomyopathy. JCI Insight, 5:133782, 2020.