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ZFIN ID: ZDB-PERS-060807-13
Oehlers, Stefan
Affiliation: Oehlers Lab
Address: Centenary Institute Locked Bag 6 Newtown NSW 2042 Australia
Phone: +61 2 9565 6192
ORCID ID: 0000-0003-0260-672X

Tuberculosis pathogenesis and host-directed therapies
Novel host-directed therapies against tuberculosis (TB) are required to overcome the threat posed by multidrug resistant Mycobacterium tuberculosis. Pathogenic mycobacteria modify or co-opt a range of evolutionarily conserved host responses to infection to successfully establish persistent granulomatous infections. We have shown that inhibiting angiogenesis in zebrafish models of mycobacterial infection reduces the growth and spread of mycobacteria by limiting the supply of oxygen to granulomas. Thrombosis is another basic and conserved response to infection that may aid the survival of mycobacteria in granulomas by redirecting the immune response.

Immune response to Cryptococcal infection
Cryptococcus neoformans is an opportunistic fungal pathogen responsible for upwards of 600,000 deaths annually and is one of the most deadly infectious afflicting AIDS patients. The related species Cryptococcus gattii is endemic to Australia and capable of causing disease even in immunocompetent people. These fungi home to the central nervous system and are capable of causing severe meningitis even with conventional treatments. Cryptococcal infection of zebrafish can be used to model this process and fungus-immune system interactions can be analysed by live imaging.

Inflammatory Bowel Disease
IBD encompasses a range of chronic inflammatory diseases affecting the gut including Crohn's Disease and Ulcerative Colitis. The aetiology of IBD is multifactorial involving an interplay for host genetics (IBD susceptibility genes) and environment (microbiota, diet and other exposures). We have utilised zebrafish models of intestinal inflammation to study the impact of susceptibility genes and the environment on IBD aetiology.

Wright, K., de Silva, K., Plain, K.M., Purdie, A.C., Blair, T.A., Duggin, I.G., Britton, W.J., Oehlers, S.H. (2021) Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis. PLoS pathogens. 17:e1009186
Cronan, M.R., Hughes, E.J., Brewer, W.J., Viswanathan, G., Hunt, E.G., Singh, B., Mehra, S., Oehlers, S.H., Gregory, S.G., Kaushal, D., Tobin, D.M. (2021) A non-canonical type 2 immune response coordinates tuberculous granuloma formation and epithelialization. Cell. 184(7):1757-1774.e14
Cholan, P.M., Han, A., Woodie, B.R., Watchon, M., Kurz, A.R., Laird, A.S., Britton, W.J., Ye, L., Holmes, Z.C., McCann, J.R., David, L.A., Rawls, J.F., Oehlers, S.H. (2020) Conserved anti-inflammatory effects and sensing of butyrate in zebrafish. Gut microbes. 12:1-11
Oehlers, S.H., Hortle, E., Cook, K.M. (2020) A zebrafish model of tuberculosis comorbidity and the effects of HIF-activating intervention. The FEBS journal. 287(18):3917-3920
Obeidy, P., Ju, L.A., Oehlers, S.H., Zulkhernain, N.S., Lee, Q., Galeano NiƱo, J.L., Kwan, R.Y., Tikoo, S., Cavanagh, L.L., Mrass, P., Cook, A.J., Jackson, S.P., Biro, M., Roediger, B., Sixt, M., Weninger, W. (2020) Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and cell biology. 98:93-113
Cheng, T., Kam, J.Y., Johansen, M.D., Oehlers, S.H. (2019) High content analysis of granuloma histology and neutrophilic inflammation in adult zebrafish infected with Mycobacterium marinum. Micron (Oxford, England : 1993). 129:102782
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
Black, H.D., Xu, W., Hortle, E., Roberston, S.I., Britton, W.J., Kaur, A., New, E.J., Witting, P.K., Chami, B., Oehlers, S.H. (2019) The cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targets. Free radical biology & medicine. 135:157-166
Johansen, M.D., Hortle, E., Kasparian, J.A., Romero, A., Novoa, B., Figueras, A., Britton, W.J., de Silva, K., Purdie, A.C., Oehlers, S.H. (2018) Analysis of mycobacterial infection-induced changes to host lipid metabolism in a zebrafish infection model reveals a conserved role for LDLR in infection susceptibility. Fish & shellfish immunology. 83:238-242
Johansen, M.D., Kasparian, J.A., Hortle, E., Britton, W.J., Purdie, A.C., Oehlers, S.H. (2018) Mycobacterium marinum infection drives foam cell differentiation in zebrafish infection models. Developmental and comparative immunology. 88:169-172
Spain, M., Wong, J.K., Nagalingam, G., Batten, J.M., Hortle, E., Oehlers, S., Jiang, X.F., Murage, H.E., Orford, J.T., Crisologo, P., Triccas, J.A., Rutledge, P.J., Todd, M.H. (2018) Anti-Tubercular bis-Substituted Cyclam Derivatives: Structure-Activity Relationships and In Vivo Studies. Journal of medicinal chemistry. 61(8):3595-3608
Alvarez, M.I., Glover, L.C., Luo, P., Wang, L., Theusch, E., Oehlers, S.H., Walton, E.M., Tram, T.T.B., Kuang, Y.L., Rotter, J.I., McClean, C.M., Chinh, N.T., Medina, M.W., Tobin, D.M., Dunstan, S.J., Ko, D.C. (2017) Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.. Proceedings of the National Academy of Sciences of the United States of America. 114(37):E7746-E7755
Oehlers, S.H., Cronan, M.R., Beerman, R.W., Johnson, M.G., Huang, J., Kontos, C.D., Stout, J.E., Tobin, D.M. (2017) Infection-induced vascular permeability aids mycobacterial growth. The Journal of infectious diseases. 215(5):813-817
Oehlers, S.H., Flores, M.V., Hall, C.J., Wang, L., Ko, D.C., Crosier, K.E., Crosier, P.S. (2017) A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation. The FEBS journal. 284(3):402-413
Cronan, M.R., Beerman, R.W., Rosenberg, A.F., Saelens, J.W., Johnson, M.G., Oehlers, S.H., Sisk, D.M., Jurcic Smith, K.L., Medvitz, N.A., Miller, S.E., Trinh, L.A., Fraser, S.E., Madden, J.F., Turner, J., Stout, J.E., Lee, S., Tobin, D.M. (2016) Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection. Immunity. 45:861-876
Matty, M.A., Oehlers, S.H., Tobin, D.M. (2016) Live Imaging of Host-Pathogen Interactions in Zebrafish Larvae. Methods in molecular biology (Clifton, N.J.). 1451:207-23
Cronan, M.R., Rosenberg, A.F., Oehlers, S.H., Saelens, J.W., Sisk, D.M., Smith, K.L., Lee, S., Tobin, D.M. (2015) CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections. Disease models & mechanisms. 8(12):1643-50
Tenor, J.L., Oehlers, S.H., Yang, J.L., Tobin, D.M., Perfect, J.R. (2015) Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion. mBio. 6(5):e01425-15
Wang, L., Oehlers, S.H., Espenschied, S.T., Rawls, J.F., Tobin, D.M., Ko, D.C. (2015) CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation. Genome biology. 16:190
Okuda, K.S., Misa, J.P., Oehlers, S.H., Hall, C.J., Ellett, F., Alasmari, S., Lieschke, G.J., Crosier, K.E., Crosier, P.S., Astin, J.W. (2015) A zebrafish model of inflammatory lymphangiogenesis. Biology Open. 4(10):1270-80
Chew, T.S., O'Shea, N.R., Sewell, G.W., Oehlers, S.H., Mulvey, C.M., Crosier, P.S., Godovac-Zimmermann, J., Bloom, S.L., Smith, A.M., Segal, A.W. (2015) Optineurin deficiency contributes to impaired cytokine secretion and neutrophil recruitment in bacteria driven colitis. Disease models & mechanisms. 8(8):817-29
Oehlers, S.H., Cronan, M.R., Scott, N.R., Thomas, M.I., Okuda, K.S., Walton, E.M., Beerman, R.W., Crosier, P.S., Tobin, D.M. (2015) Interception of host angiogenic signalling limits mycobacterial growth. Nature. 517(7536):612-5
Hall, C.J., Boyle, R.H., Astin, J.W., Flores, M.V., Oehlers, S.H., Sanderson, L.E., Ellett, F., Lieschke, G.J., Crosier, K.E., and Crosier, P.S. (2013) Immunoresponsive Gene 1 Augments Bactericidal Activity of Macrophage-Lineage Cells by Regulating β-Oxidation-Dependent Mitochondrial ROS Production. Cell Metabolism. 18(2):265-278
Oehlers, S.H., Flores, M.V., Hall, C.J., Okuda, K.S., Sison, J.O., Crosier, K.E., and Crosier, P.S. (2013) Chemically Induced Intestinal Damage Models in Zebrafish Larvae. Zebrafish. 10(2):184-93
Oehlers, S.H., Flores, M.V., Hall, C.J., Crosier, K.E., and Crosier, P.S. (2012) Retinoic acid suppresses intestinal mucus production and exacerbates experimental enterocolitis. Disease models & mechanisms. 5(4):457-467
Hall, C.J., Flores, M.V., Oehlers, S.H., Sanderson, L.E., Lam, E.Y., Crosier, K.E., and Crosier, P.S. (2012) Infection-Responsive Expansion of the Hematopoietic Stem and Progenitor Cell Compartment in Zebrafish Is Dependent upon Inducible Nitric Oxide. Cell Stem Cell. 10(2):198-209
Crawford, K.C., Flores, M.V., Oehlers, S.H., Hall, C.J., Crosier, K.E., and Crosier, P.S. (2011) Zebrafish heat shock protein a4 genes in the intestinal epithelium are up-regulated during inflammation. Genesis (New York, N.Y. : 2000). 49(12):905-11
Oehlers, S.H., Flores, M.V., Hall, C.J., Swift, S., Crosier, K.E., and Crosier, P.S. (2011) The inflammatory bowel disease (IBD) susceptibility genes NOD1 and NOD2 have conserved anti-bacterial roles in zebrafish. Disease models & mechanisms. 4(6):832-41
Oehlers, S.H., Flores, M.V., Chen, T., Hall, C.J., Crosier, K.E., and Crosier, P.S. (2011) Topographical distribution of antimicrobial genes in the zebrafish intestine. Developmental and comparative immunology. 35(3):385-391
Oehlers, S.H., Flores, M.V., Okuda, K.S., Hall, C.J., Crosier, K.E., and Crosier, P.S. (2011) A chemical enterocolitis model in zebrafish larvae that is dependent on microbiota and responsive to pharmacological agents. Developmental dynamics : an official publication of the American Association of Anatomists. 240(1):288-298
Oehlers, S.H., Flores, M.V., Hall, C.J., O'Toole, R., Swift, S., Crosier, K.E., and Crosier, P.S. (2010) Expression of zebrafish cxcl8 (interleukin-8) and its receptors during development and in response to immune stimulation. Developmental and comparative immunology. 34(3):352-359