Dr Stefan Oehlers

Research Fellow, Central Clinical School and Marie Bashir Institute
Associate Faculty, Immune-Vascular Interactions Lab, Tuberculosis Research Program, Centenary Institute

Telephone 02 9565 6192

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Biographical details

BSc and BSc(Hons), Univeristy of Auckland 2004-2007

PhD, University of Auckland 2008-2012

Postdoc, Duke University Medical Centre 2012-2016

Research interests

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.

Atherogenesis

Atherosclerosis and complications from atherosclerotic plaques are a leading cause of death and disability in Australia. Interestingly, the atherosclerotic plaque, or atheroma, shares many similarities with the tuberculosis granuloma. I am interested in drawing parallels between these pathological structures to understand how atherosclerotic plaques form and rupture.

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.

Current projects

Available for Honours, Masters, and PhD study.

Targeting host vasculature as a novel therapy for mycobacterial infections

Angiogenesis, vascular leakiness, and haemostasis are seen around sites of active TB infection called granulomas. We have shown that stopping the growth of blood vessels towards granulomas (anti-angiogenic therapy), inhibition of vascular leakiness, or inhibiting the activation of platelets also reduce mycobacterial growth. Current projects at include determining the mechanism(s) of action of these therapies using a range of experimental models, and validating these therapies into mammalian models of TB infection.

Live imaging atherogenesis

The paradigm of foamy macrophages and lipid accumulation in the walls of blood vessels is well known. However, our understanding of the basic cellular dynamics that take place in atherogenesis has been limited by our inability to image the vessels in which these processes take place with appropriate resolution. We are applying the zebrafish model to characterise immune cell dynamics during atherogenesis, and investigate the importance of vascular remodelling and leakage in fuelling atheroma pathology.

Live imaging the immune response to cryptococcus infection

In collaboration with University of Sydney cryptococcal research groups, we are using zebrafish as an infection model to determine how the fungus evades or subverts the immune response to establish infection and cause disease.

Awards and honours

2018 Richard Perham Prize (FEBS)

In the media

Media coverage for "Interception of host angiogenic signalling limits mycobacterial growth" https://nature.altmetric.com/details/2919238

Media coverage for "Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion" https://www.altmetric.com/details/4566991

International links

United States

(Duke University Medical Center) Ongoing zebrafish-Mycobacterium marinum research projects with postdoctoral mentor Dr David Tobin

Selected grants

2018

  • Zebrafish models of mycobacterial infection; Oehlers S, Grau G; DVC Research/Postdoctoral Research Fellowship Scheme.
  • Live imaging endothelial-immune interactions in atherogenesis; Oehlers S; NSW Health/Early Mid Career Fellowship.

2013

  • Identification of Mycobacterial Gene Products that Modulate Host Inflammation; Oehlers S; National Health and Medical Research Council (NHMRC)/Early Career Fellowships.

Selected publications

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Book Chapters

  • Matty, M., Oehlers, S., Tobin, D. (2016). Live Imaging of Host�Pathogen Interactions in Zebrafish Larvae. In Koichi Kawakami, E. Elizabeth Patton, & Michael Orger (Eds.), Zebrafish: Methods and Protocols, (pp. 207-223). New York: Springer Science+Business Media. [More Information]

Journals

  • Johansen, M., Hortle, E., Kasparian, J., Romero, A., Novoa, B., Figueras, A., Britton, W., de Silva, K., Purdie (Williams), A., Oehlers, S. (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 and Shellfish Immunology, 83, 238-242. [More Information]
  • Spain, M., Wong, J., Nagalingam, G., Batten, J., Hortle, E., Oehlers, S., Jiang, X., Murage, H., Orford, J., Crisologo, P., Triccas, J., Rutledge, P., Todd, M. (2018). Antitubercular bis-substituted cyclam derivatives: Structure-activity relationships and in vivo studies. Journal of Medicinal Chemistry, 61(8), 3595-3608. [More Information]
  • Johansen, M., Kasparian, J., Hortle, E., Britton, W., Purdie (Williams), A., Oehlers, S. (2018). Mycobacterium marinum infection drives foam cell differentiation in zebrafish infection models. Developmental and Comparative Immunology, 88, 169-172. [More Information]
  • Namivandi-Zangeneh, R., Kwan, R., Nguyen, T., Yeow, J., Byrne, F., Oehlers, S., Wong, E., Boyer, C. (2018). The effects of polymer topology and chain length on the antimicrobial activity and hemocompatibility of amphiphilic ternary copolymers. Polymer Chemistry, 9(13), 1735-1744. [More Information]
  • Oehlers, S., Flores, M., Hall, C., Wang, L., Ko, D., Crosier, K., Crosier, P. (2017). A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation. The FEBS Journal, 284(3), 402-413. [More Information]
  • Alvarez, M., Glover, L., Luo, P., Wang, L., Theusch, E., Oehlers, S., Walton, E., Tram, T., Kuang, Y., Rotter, J., et al (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. [More Information]
  • Oehlers, S., Cronan, M., Beerman, R., Johnson, M., Huang, J., Kontos, C., Stout, J., Tobin, D. (2017). Infection-induced vascular permeability aids mycobacterial growth. The Journal of Infectious Diseases, 215(5), 813-817. [More Information]
  • Okuda, K., Misa, J., Oehlers, S., Hall, C., Ellett, F., Alasmari, S., Lieschke, G., Crosier, K., Croiser, P., Astin, J. (2015). A zebrafish model of inflammatory lymphangiogenesis. Biology Open, 4(10), 1270-1280. [More Information]
  • Cronan, M., Rosenberg, A., Oehlers, S., Saelens, J., Sisk, D., Jurcic Smith, K., Lee, S., Tobin, D. (2015). CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections. Disease Models & Mechanisms, 8(12), 1643-1650. [More Information]
  • Wang, L., Oehlers, S., Espenschied, S., Rawls, J., Tobin, D., Ko, D. (2015). CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation. Genome Biology, 16(1), 1-18. [More Information]
  • Oehlers, S., Cronan, M., Scott, N., Thomas, M., Okuda, K., Walton, E., Beerman, R., Crosier, P., Tobin, D. (2015). Interception of host angiogenic signalling limits mycobacterial growth. Nature, 517(7536), 612-615. [More Information]
  • Tenor, J., Oehlers, S., Yang, J., Tobin, D., Perfect, J. (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), 1-11. [More Information]

2018

  • Johansen, M., Hortle, E., Kasparian, J., Romero, A., Novoa, B., Figueras, A., Britton, W., de Silva, K., Purdie (Williams), A., Oehlers, S. (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 and Shellfish Immunology, 83, 238-242. [More Information]
  • Spain, M., Wong, J., Nagalingam, G., Batten, J., Hortle, E., Oehlers, S., Jiang, X., Murage, H., Orford, J., Crisologo, P., Triccas, J., Rutledge, P., Todd, M. (2018). Antitubercular bis-substituted cyclam derivatives: Structure-activity relationships and in vivo studies. Journal of Medicinal Chemistry, 61(8), 3595-3608. [More Information]
  • Johansen, M., Kasparian, J., Hortle, E., Britton, W., Purdie (Williams), A., Oehlers, S. (2018). Mycobacterium marinum infection drives foam cell differentiation in zebrafish infection models. Developmental and Comparative Immunology, 88, 169-172. [More Information]
  • Namivandi-Zangeneh, R., Kwan, R., Nguyen, T., Yeow, J., Byrne, F., Oehlers, S., Wong, E., Boyer, C. (2018). The effects of polymer topology and chain length on the antimicrobial activity and hemocompatibility of amphiphilic ternary copolymers. Polymer Chemistry, 9(13), 1735-1744. [More Information]

2017

  • Oehlers, S., Flores, M., Hall, C., Wang, L., Ko, D., Crosier, K., Crosier, P. (2017). A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation. The FEBS Journal, 284(3), 402-413. [More Information]
  • Alvarez, M., Glover, L., Luo, P., Wang, L., Theusch, E., Oehlers, S., Walton, E., Tram, T., Kuang, Y., Rotter, J., et al (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. [More Information]
  • Oehlers, S., Cronan, M., Beerman, R., Johnson, M., Huang, J., Kontos, C., Stout, J., Tobin, D. (2017). Infection-induced vascular permeability aids mycobacterial growth. The Journal of Infectious Diseases, 215(5), 813-817. [More Information]

2016

  • Matty, M., Oehlers, S., Tobin, D. (2016). Live Imaging of Host�Pathogen Interactions in Zebrafish Larvae. In Koichi Kawakami, E. Elizabeth Patton, & Michael Orger (Eds.), Zebrafish: Methods and Protocols, (pp. 207-223). New York: Springer Science+Business Media. [More Information]

2015

  • Okuda, K., Misa, J., Oehlers, S., Hall, C., Ellett, F., Alasmari, S., Lieschke, G., Crosier, K., Croiser, P., Astin, J. (2015). A zebrafish model of inflammatory lymphangiogenesis. Biology Open, 4(10), 1270-1280. [More Information]
  • Cronan, M., Rosenberg, A., Oehlers, S., Saelens, J., Sisk, D., Jurcic Smith, K., Lee, S., Tobin, D. (2015). CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections. Disease Models & Mechanisms, 8(12), 1643-1650. [More Information]
  • Wang, L., Oehlers, S., Espenschied, S., Rawls, J., Tobin, D., Ko, D. (2015). CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation. Genome Biology, 16(1), 1-18. [More Information]
  • Oehlers, S., Cronan, M., Scott, N., Thomas, M., Okuda, K., Walton, E., Beerman, R., Crosier, P., Tobin, D. (2015). Interception of host angiogenic signalling limits mycobacterial growth. Nature, 517(7536), 612-615. [More Information]
  • Tenor, J., Oehlers, S., Yang, J., Tobin, D., Perfect, J. (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), 1-11. [More Information]

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