Harder Lab - Publications

Selected Publications

Roberts ME, Bishop JL, Fan X, Beer JL, Kum WW, Krebs DL, Huang M, Gill N, Priatel JJ, Finlay BB, Harder KW. Lyn Deficiency Leads to Increased Microbiota-Dependent Intestinal Inflammation and Susceptibility to Enteric Pathogens. J Immunol. 2014 Nov 15;193(10):5249-63.

Bishop JL, Roberts ME, Beer JL, Huang M, Chehal MK, Fan X, Fouser LA, Ma HL, Bacani JT, Harder KW. Lyn activity protects mice from DSS colitis and regulates the production of IL-22 from innate lymphoid cells. Mucosal Immunol. 2014 Mar;7(2):405-16.

Sio A, Chehal MK, Tsai K, Fan X, Roberts ME, Nelson BH, Grembecka J, Cierpicki T, Krebs DL, Harder KW. Dysregulated hematopoiesis caused by mammary cancer is associated with epigenetic changes and hox gene expression in hematopoietic cells. Cancer Res. 2013 Oct 1;73(19):5892-904.

Krebs DL, Chehal MK, Sio A, Huntington ND, Da ML, Ziltener P, Inglese M, Kountouri N, Priatel JJ, Jones J, Tarlinton DM, Anderson GP, Hibbs ML, Harder KW. Lyn-dependent signaling regulates the innate immune response by controlling dendritic cell activation of NK cells. J Immunol. 2012 May 15;188(10):5094-105.

Harder KW, Quilici C, Naik E, Inglese M, Kountouri N, Turner A, Zlatic K, Tarlinton DM, Hibbs ML. Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1. Blood. 2004 Dec 15;104(13):3901-10. 

Harder KW, Parsons LM, Armes J, Evans N, Kountouri N, Clark R, Quilici C, Grail D, Hodgson GS, Dunn AR, Hibbs ML. Gain- and loss-of-function Lyn mutant mice define a critical inhibitory role for Lyn in the myeloid lineage. Immunity. 2001 Oct;15(4):603-15. (Featured Article)

Xu Y, Harder KW, Huntington ND, Hibbs ML, Tarlinton DM. Lyn tyrosine kinase: accentuating the positive and the negative. Immunity. 2005 Jan;22(1):9-18. Review.

Other Publications

Tsantikos E, Maxwell MJ, Kountouri N, Harder KW, Tarlinton DM, Hibbs ML.. Genetic interdependence of Lyn and negative regulators of B cell receptor signaling in autoimmune disease development. J Immunol. 2012 Aug 15;189(4):1726-36.

Xu Y, Huntington ND, Harder KW, Nandurkar H, Hibbs ML, Tarlinton DM. Phosphatidylinositol-3 kinase activity in B cells is negatively regulated by Lyn tyrosine kinase. Immunol Cell Biol. 2012 Oct;90(9):903-11.

Nijnik A, Pistolic J, Cho P, Filewod NC, Falsafi R, Ramin A, Harder KW, Hancock RE. The role of the Src family kinase Lyn in the immunomodulatory activities of cathelicidin peptide LL-37 on monocytic cells. J Leukoc Biol. 2012 Apr;91(4):599-607.

Shio MT, Eisenbarth SC, Savaria M, Vinet AF, Bellemare MJ, Harder KW, Sutterwala FS, Bohle DS, Descoteaux A, Flavell RA, Olivier M. Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases.
PLoS Pathog. 2009 Aug;5(8):e1000559.

Tsantikos E, Quilici C, Harder KW, Wang B, Zhu HJ, Anderson GP, Tarlinton DM, Hibbs ML..Perturbation of the CD4 T cell compartment and expansion of regulatory T cells in autoimmune-prone Lyn-deficient mice. J Immunol. 2009 Aug 15;183(4):2484-94.

Priatel JJ, Chen X, Zenewicz LA, Shen H, Harder KW, Horwitz MS, Teh HS. Chronic immunodeficiency in mice lacking RasGRP1 results in CD4 T cell immune activation and exhaustion. J Immunol. 2007 Aug 15;179(4):2143-52.

McColl BK, Paavonen K, Karnezis T, Harris NC, Davydova N, Rothacker J, Nice EC, Harder KW, Roufail S, Hibbs ML, Rogers PA, Alitalo K, Stacker SA, Achen MG. Proprotein convertases promote processing of VEGF-D, a critical step for binding the angiogenic receptor VEGFR-2. FASEB J. 2007 Apr;21(4):1088-98.

Ingley, E., Schneider J.R., McCarthy D.J., Harder K.W., Hibbs, M.L. and Klinken, S.P. (2006). Cbp mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells. J. Biol. Chem.  20;281(42), 31920-9.

Hibbs ML, Harder KW. The duplicitous nature of the Lyn tyrosine kinase in growth factor signaling. Growth Factors. 2006 Jun;24(2):137-49.

Beavitt SJ, Harder KW, Kemp JM, Jones J, Quilici C, Casagranda F, Lam E, Turner D, Brennan S, Sly PD, Tarlinton DM, Anderson GP, Hibbs ML.. Lyn-deficient mice develop severe, persistent asthma: Lyn is a critical negative regulator of Th2 immunity. J Immunol. 2005 Aug 1;175(3):1867-75.

Harder KW, Quilici C, Naik E, Inglese M, Kountouri N, Turner A, Zlatic K, Tarlinton DM, Hibbs ML. Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1. Blood. 2004 Dec 15;104(13):3901-10. Epub 2004 Aug 31.

Odom S, Gomez G, Kovarova M, Furumoto Y, Ryan JJ, Wright HV, Gonzalez-Espinosa C, Hibbs ML, Harder KW, Rivera J. Negative regulation of immunoglobulin E-dependent allergic responses by Lyn kinase. J Exp Med. 2004 Jun 7;199(11):1491-502. 

Stenvers, K.L., Tursky, M.L., Harder, K.W., Kountouri, N., Amatayakul-Chantler, S., Grail, D., Small, C., Weinberg, R.A., Sizeland, A.M., and Zhu, H-J. (2003). Heart and liver defects and reduced transforming growth factor-b2 sensitivity in transforming growth factor-b type III receptor-deficient embryos. Mol. Cell. Biol. 12, 4371-4385.

Hibbs ML, Harder KW, Armes J, Kountouri N, Quilici C, Casagranda F, Dunn AR, Tarlinton DM. Sustained activation of Lyn tyrosine kinase in vivo leads to autoimmunity. J Exp Med. 2002 Dec 16;196(12):1593-604.

Xu, Y., Beavitt, S-J., Harder, K.W., Hibbs, M.L., Tarlinton, D.M. (2002). The activation and subsequent regulatory roles of Lyn and CD19 after B cell receptor ligation are independent. J. Immunol. 169, 6910-6918.

Ernst, M., Inglese, M., Scholz, G.M., Harder, K.W., Clay, F.J., Bozinovski, S., Waring, P., Darwiche, R., Kay, T., Sly, P., Collins, R., Turner, D., Hibbs M.L., Anderson, G.P., and Dunn, A.R. (2002). Constitutive activation of the Src-family kinase Hck results in spontaneous pulmonary inflammation and an enhanced innate immune response. J. Exp. Med. 196 (5), 589-604. (featured on cover)

Lei, G., Xue, S., Chery, N., Liu, Q., Xu, J., Kwan, C.L., Fu, Y.P., Lu, Y.M., Liu, M., Harder, K.W., Yu, X.M. (2002). Gain control of N-methyl-D-aspartate receptor activity by receptor-like protein tyrosine phosphatase alpha. EMBO J. 21 (12), 2977-2989.

Harder, K.W., Moller, N.P.H., Peacock, J., Jirik, F. (1998). Protein-tyrosine phosphatase alpha regulates Src family kinases and alters cell-substratum adhesion. J. Biol. Chem. 273(48), 31890-31900.

Ng, D.H., Jabali, M.D., Maiti, A., Borodchak, P., Harder, K.W., Brocker, T., Malissen, B., Jirik, F.R., Johnson, P. (1997). CD45 and RPTPa display different protein tyrosine phosphatase activities in T lymphocytes. Biochem. J. 327, 867-876.

Harder, K.W., Saw, J., Miki, N., and Jirik, F. (1995). Coexisting amplifications of the chromosome 1p32 genes (PTPRF and MYCL1) encoding protein tyrosine phosphatase LAR and L-myc in a small cell lung cancer line. Genomics 27, 552-553.

Amankwa, L.N., Harder, K.W., Jirik, F., and Aebersold, R. (1995). High-sensitivity determination of tyrosine-phosphorylated peptides by on-line enzyme reactor and electrospray ionization mass spectrometry. Protein Sci. 4, 113-125.

Ng, D.H., Harder, K.W., Clark-Lewis, I., Jirik, F., and Johnson, P. (1995). Non-radioactive method to measure CD45 protein tyrosine phosphatase activity isolated directly from cells. J. Immunol. Methods 179, 177-185.

Dechert, U., Affolter, M., Harder, K.W., Matthews, J., Owen, P., Clark-Lewis, I., Thomas, M.L., Aebersold, R., Jirik, F.R. (1995). Comparison of the specificity of bacterially expressed cytoplasmic protein-tyrosine phosphatases SHP and SH-PTP2 towards synthetic phospho-peptide substrates. Eur. J. Biochem. 231, 673-81.

Halleck, M.S., Pownall, S., Harder, K.W., Duncan, A.M., Jirik, F.R., Schlegel, R.A. (1995). A widely distributed putative mammalian transcriptional regulator containing multiple paired amphipathic helices with similarity to yeast SIN3.Genomics 26, 403-6.

Dechert, U., Adam, M., Harder, K.W., Clark-Lewis, I., and Jirik, F. (1994). Characterization of protein tyrosine phosphatase SH-PTP2. J. Biol. Chem. 269, 5602-5611.

Harder, K.W., Owen, P., Wong, L.K.H., Aebersold, R., Clark-Lewis, I., and Jirik, F.R. (1994). Characterization and kinetic analysis of the intracellular domain of human protein tyrosine phosphatase b (HPTPb) using synthetic phosphopeptides. Biochem. J. 298, 395-401.

Roberge, M., Tudan, C., Hung, S.M., Harder, K.W., Jirik, F.R., and Anderson, H. (1994). Antitumor drug fostriecin inhibits the mitotic entry checkpoint and protein phosphatases 1 and 2A. Cancer Res. 54, 6115-6121.

Charest, D.L., Mordret, G., Harder, K.W., Jirik, F., and Pelech, S.L. (1993). Molecular cloning, expression, and characterization of the human mitogen-activated protein kinase p44erk1. Mol. Cell. Biol. 13, 4679-4690.

Harder, K.W., Anderson, L.L., Duncan, A.M.V., and Jirik, F.R. (1992). The gene for receptor-like protein tyrosine phosphatase (PTPRB) is assigned to chromosome 12q15--q21. Cytogenet. Cell Genet. 61, 269-270.

Jirik, F.R., Harder, K.W., Melhado, I.G., Anderson, L.L., and Duncan, A.M.V. (1992). The gene for leukocyte antigen-related tyrosine phosphatase (LAR) is localized to human chromosome 1p32, a region frequently deleted in tumors of neuroectodermal origin. Cytogenet. Cell Genet. 61, 266-268.

Jirik, F.R., Janzen, N.M., Melhado, I.G., and Harder, K.W. (1990). Cloning and chromosomal assignment of a widely expressed human receptor-like protein-tyrosine phosphatase. FEBS Lett. 273, 239-242.