Kindrachuk, Jason - University of Manitoba - Department of Medical Microbiology and Infectious Diseases

研究领域

Emerging/re-emerging viruses pose a significant threat to global public health, and outbreaks of these pathogens have increased in frequency as a result of changing socio-economic, environmental, and ecological factors. In recent years, multiple zoonotic viruses, including Ebola virus (EBOV), severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), and Zika virus, have emerged as global public health threats. Emerging/re-emerging viruses often result in severe illness and complex pathogenesis and the molecular processes driving these events are poorly understood. A multidisciplinary approach is required to elucidate emerging/re-emerging viral pathogenesis, improve clinical management, and facilitate therapeutic discovery. Advanced molecular techniques are also needed to further validate current animal models to human disease. My research program addresses multiple critical areas of research including: 1) characterization of the molecular pathogenesis of emerging/re-emerging viruses with a focus on the role of dyregulated barrier function in disease pathogenesis; 2) assessment of alterations to kinase-mediated cell signaling in host cells or tissues during emerging and re-emerging viral infection through kinome analysis; 3) identification and assessment of kinase inhibitors as novel host-targeted antiviral therapeutics; and 4) the identification of disease biomarkers and therapeutic targets from patient samples of severe viral infections

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Falcinelli, S.D., Chertow, D.S., and KINDRACHUK, J. (2016) Integration of Global Analyses of Host Molecular Responses with Clinical Data to Evaluate Pathogenesis and Advance Therapies for Emerging and Re-Emerging Viral Infections. ACS Infect Dis. 2: 787-799. Davis, S.A.*, Chertow, D.S.*, KINDRACHUK, J., Schwartzman, L.M., Suzich, J., Alsaaty, S., Logun, C., Shelhamer, J.H., and Taubenberger, J.K. (2016) 1918 Influenza Receptor Binding Domain Variants Bind and Replicate in Primary Human Airway Cells Regardless of Receptor Specificity. Virology. 493: 283-246. *Authors contributed equally to this work Chertow, D.S., KINDRACHUK, J., Sheng, Z.M., Pujanauski, L., Cooper, K., Nogee, D., St. Claire, M., Solomon, J., Perry, D., Sayre, P., Janosko, K.B., Lackemeyer, M.G., Bohannon, J.K., Hensley, L.E., Kash, J.C., Jahrling, P.B. and Taubenberger, J.K. (2016) An experimental model of lung injury in rhesus macaques following influenza and bacterial co-infection. Antiviral Res. 129: 120-9. Walters, K.A., D’Agnillo, F., Sheng, Z.M., KINDRACHUK, J., Schwartzman, L.M., Keustner, R.E., Chertow, D.S., Golding, B., Taubenberger, J.K. and Kash, J.C. (2016) 1918 pandemic influenza virus and Streptococcus pneumoniae coinfection results in activation of coagulation and widespread pulmonary microvascular thrombosis in mice and humans. J Pathol. 238: 85-97. Falcinelli, S., Gowen, B., Trost, B., Napper, S., Kusalik, A., Safronetz, D., Prescott, J., Johnson, R.F., Wahl-Jensen, V. Jahrling, P.B. and KINDRACHUK, J. (2015) Characterization of the functional host response to Pichinde virus infection in the Syrian golden hamster. Mol Cell Proteomics. 14: 646-57. KINDRACHUK, J., Ork, B., Hart, B., Holbrook, M., Frieman, M., Johnson, R.F., Dyall, J., Olinger, G.G., Hensley, L.E., Jahrling, P.B., and KINDRACHUK, J. (2015) Temporal kinome analysis demonstrates that MERS-CoV selectively modulates ERK/MAPK and PI3K/AKT/mTOR signaling. Antimicrob Agents Chemother. 59: 1088-99. Kuhn, J.H., Andersen, K.G., Bào, Y., Bavari, S., Becker, S., Bennett, R.S., Bergman, N.H., Blinkova, O., Bradfute, S., Brister, J.R., Bukreyev, A., Chandran, K., Chepurnov, A.A., Davey, R.A., Dietzgen, R.G., Doggett, N.A., Dolnik, O., Dye, J.M., Enterlein, S., Fenimore, P.W., Formenty, P., Freiberg, A.N., Garry, R.F., Garza, N.L., Gire, S.K., Gonzalez, J.P., Griffiths, A., Happi, C.T., Hensley, L.E., Herbert, A.S., Hevey, M.C., Hoenen, T., Honko, A.N., Ignatyev, G.M., Jahrling, P.B., Johnson, J.C., Johnson, K.M., KINDRACHUK, J., et al. (2014) Filovirus RefSeq entries: evaluation and selection of filovirus type variants, type sequences, and names. Viruses. 6: 3663-82. KINDRACHUK, J.*, Wahl-Jensen, V.*, Safronetz, D., Arsenault, R., Hoenen, T., Traynor, D., Postnikova, E., Napper, S., Blaney, J.E., and Jahrling, P.B. (2014) Temporal systems kinomics demonstrates that Ebola virus infection selectively modulates transforming growth factor β signaling in hepatocytes. J Virol. 88: 9877-92. *Authors contributed equally Dyall, J., Coleman, C., Hart, B., Venkataraman, T., Holbrook, M., KINDRACHUK, J., Johnson, R.F., Olinger, G.G., Jahrling, P.B., Laidlaw, M., Johnson, L., Glass, P., Hensley, L.E., and Frieman, M. (2014) Discovery of FDA-approved inhibitors of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 58: 4885-93. Jahrling, P.B., Lauren, K., St. Claire, M., Johnson, R., Bollinger, L., Lackemeyer, M., Hensley, L., KINDRACHUK, J., and Kuhn, J.H. (2014) Medical management and imaging of animals infected with risk group 4 pathogens at the NIAID Integrated Research Facility at Fort Detrick, Maryland. Pathog Dis. 71: 213-9. KINDRACHUK, J., Falcinelli, S., Wada, J., Kuhn, J.H., Hensley, L.E., and Jahrling, P.B. (2014) Systems kinomics: a new paradigm for characterizing host responses to high consequence pathogens at the NIH/NIAID Integrated Research Facility at Frederick, MD. Pathog Dis. 71: 190-98. Lackemeyer, M.G., de Kok-Mercado, F., Wada, J., KINDRACHUK, J., Wahl-Jensen, V., Kuhn, J.H., and Jahrling, P.B. (2014) ABSL-4 aerobiology biosafety and technology at the NIH/NIAID Integrated Research Facility at Fort Detrick. Viruses. 6: 137-50. Hart, B.J., Dyall, J., Postnikova, E., Zhou, H., KINDRACHUK, J., Johnson, R.F., Olinger, G.G., Jahrling, P.B. and Hensley, L. (2014) Interferon-beta and mycophenolic acid are potent inhibitors of MERS-CoV in cell-based assays. J Gen Virol. 95: 571-7. Trost, B., KINDRACHUK, J., Maattanen, P., Napper, S., and Kusalik, A. (2013) PIIKA 2: novel tools for the analysis of kinome microarray data. PLoS ONE. 8: e80837. Trost, B., KINDRACHUK, J., Scruten, E., Griebel, P., Kusalik, A. and Napper, S. (2013) Personalized profiles of cellular kinase activity: the kinotype. BMC Genomics 14: 854. KINDRACHUK, J., Jenssen, H., Elliott, M., Nijnik, A., Fang, Y., Pistolic, J., Pasupuleti, M., Thorson, L., Ma, S., Easton, D., Bains, M., Arnusch, C.J., Finlay, B., Sahl, H.G., Breukink, E. and Hancock, R.E.W. (2013) Manipulation of innate immunity by a bacterial secreted peptide: lantibiotic nisin Z is selectively immunomodulatory. Innate Immun. 19: 315-27. Achtman, A.H., Pilat, S., Law, C.W., Lynn, D.J., Janot, L., Ma, S., KINDRACHUK, J., Finlay, B.B., Brinkman, F.S.L., Smyth, G.K., Hancock, R.E.W., and Schofield, L. (2012) Effective adjunctive therapy by an innate defense regulatory peptide in a preclinical model of severe malaria. Sci Transl Med. 4: 135ra64. Steinstraesser, L., Hirsch, T., Schulte, M., Kueckelhaus, M., Jacobsen, F., Mersch, E., Al-Benna, S., Stricker, I., Afacan, N., Jenssen, H., Hancock, R.E. and KINDRACHUK, J. (2012) Innate defense regulator peptide 1018 in wound healing and wound infection. PLoS One. 7: e39373. KINDRACHUK, J., Arsenault, R., Kusalik, T., Kindrachuk, K.N., Trost, B., Napper, S., Jahrling, P.B. and Blaney, J.E. (2012) Systems kinomics demonstrates Congo Basin Monkeypox virus infection selectively modulates host cell signaling responses as compared to West African Monkeypox virus. Mol Cell Proteomics.11: M.111.015701. Gao, G.*, Cheng, J.T.*, KINDRACHUK, J., Hancock, R.E.W., Straus, S.K. and Kizhakkedathu, J. (2011) Biomembrane interactions of polymer brush and soluble polymer tethered host defence IDR-1010: Insight into the mechanism of action of surface immobilized peptides. Chem Bio. 19: 199-209. *Authors contributed equally to this work Gao, G., Yu, K., KINDRACHUK, J., Brooks, D.E., Hancock, R.E.W., and Kizhakkedathu, J.N. (2011) Antibacterial surfaces based on polymer brushes: Investigation on the influence of brush properties on antimicrobial peptide immobilization and antimicrobial activity. Biomacromolecules. 32: 3899-909. Wahl-Jensen, V.*, Kurz, S.*, Buehler, L.K., KINDRACHUK, J., DeFilippis, V., da Silva, J., Fruh, K., Kuhn, J.H., Burton, D.R. and Feldmann, H. (2011) Ebola virion binding to and entry into human macrophages profoundly effects cellular gene expression prior to expression of virus proteins. PLoS Negl Trop Dis.5: e1359. *Authors contributed equally to this work Garlapati, S.*, Eng, N.F.*, Kiros, T., KINDRACHUK, J., Mutwiri, G.K., Hancock, R.E., Babiuk, L.A. and Gerdts, V. (2011) Immunization with PCEP microparticles containing pertussis toxoid, CpG ODN and a synthetic innate defense regulator peptide induces protective immunity against pertussis. Vaccine. 29: 6540-8.*Authors contributed equally to this work McAndrew Lynn, M.A., KINDRACHUK, J., Jenssen, H., Pante, N., Elliott, M., Napper, S., Hancock, R.E.W., and McMaster, R. (2011) Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. PLoS Negl Trop Dis. 5: e1141. Gao, G.*, Lange, D.*, Hilpert, K., KINDRACHUK, J., Zou, Y., Cheng, J.T., Kazemzadeh, M., Yu, K., Wang, R., Straus, S.K., Brooks, D.E., Chew, B.H., Hancock, R.E. and Kizhakkedathu, J.N. (2011) The biocompatibility and biofilm resistance of implant coatings based on hydrophilic polymer brushes conjugated with antimicrobial peptides. Biomaterials. 32: 3899-909.