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Department of Pharmacology and Toxicology staff profiles

Dr Lyn Wise

PositionSenior Lecturer
DepartmentDepartment of Pharmacology and Toxicology
QualificationsBSc(Hons) PhD
Research summaryVirology, skin infections, angiogenesis, inflammation, wound healing, therapeutics

Research

I trained as a molecular virologist and was a key researcher in the functional characterisation of the viral family of vascular endothelial growth factors and a range of anti-inflammatory factors encoded by the parapoxviruses.

My research currently focuses on microbial manipulation of the inflammatory, vascular and wound healing responses in the skin, and the use of bio-therapeutics for skin wounds, infections and inflammatory disorders.

My interests are centered around three overlapping themes; how do microbes manipulate the tissue around them, what does this tell us about our own physiology and can we exploit this knowledge to develop new drugs for treating infections and other pathologies.




Current Research:

Our research aim is to understand how the body, particularly the skin, can heal itself after damage caused by trauma or infection.

The approach we are taking is to harness natural agonists of the healing responses and develop them as therapeutics for when our bodies fail to heal. The agonists we are developing come from our own skin cells or microbes, and from NZ’s native flora, fauna and agricultural byproducts.

Our goals are to use these natural therapeutics to accelerate healing of chronic ulcers and skin burns, and to reduce the scarring that occurs following trauma or surgery. We are looking to use these agonists to treat both human and veterinary conditions. We are also exploring the utility of these therapeutics for other parts of the body suffering from damage or impaired healing. This includes the brain following stroke or injury, fibrotic lungs, irritated bowels and various tumours.


Past and present funding:

  • The Health Research Council of New Zealand.
  • The New Zealand Equine Research Foundation.
  • Otago Innovation Ltd.
  • The University of Otago.
  • The Otago Medical Research Foundation.
  • HalcyGen Pharmaceuticals Limited.

Current Collaborations:

  • Professor Andrew Mercer and Dr Stephen Fleming, Department of Microbiology and Immunology, University of Otago.
  • Professor Chris Jackson, Kolling Institute of Medical Research, University of Sydney.
  • Professor Kurt Krause, Dr Monica Gerth and Dr Anita Dunbier, Department of Biochemistry, University of Otago.
  • Associate Professor Tim Woodfield and Dr Khoon Lim, Department of Orthopaedic Surgery and Centre for Bioengineering & Nanomedicine, University of Otago Christchurch.
  • Associate Professor Michael Stitely, Department of Women’s and Children’s Health, University of Otago.
  • Professor Christine Theoret, Département de Biomédecine Vétérinaire, Université de Montréal.
  • Professor Chris Riley, Institute of Vet, Animal and Biomedical Sciences, Massey University.
  • Associate Professor Merilyn Hibma and Dr Heather Cunliffe, Department of Pathology, University of Otago.
  • Dr Georgina Dowd, Marine Products Group, Plant & Food Research.

Current Group Members:


Wise

Wise Lab Group June 2017
(Back, left-right): Zabeen Lateef, Lauren Collins, Rory Burgess, Gabriella Stuart.
(Front, left-right): Lyn Wise, Nicky Real.

Principal Investigator

Dr Lyn Wise
Email lyn.wise@otago.ac.nz
Office: +64 479 7723
Lab: +64 479 5720

Postdoctoral Fellow

Dr Zabeen Lateef
Email zabeen.lateef@otago.ac.nz
Office: +64 479 4174
Lab: +64 479 5720
Project: Viral proteins as novel therapeutics for human skin wounds.


Research Technicians

Gabriella Stuart
Email gabriella.stuart@otago.ac.nz
Nicola Real
Email nicky.real@otago.ac.nz
Office: +64 479 4174
Lab: +64 479 5720
Project: Viral proteins as novel therapeutics for human skin wounds.


Postgraduate Students


Lauren Collins, BSc Hons (Genetics)
Project: Interleukin-10 and fibroproliferative disorders in horses.

Rory Burgess, PGDipSc (Pharmacology)
Project: Development and screening of a SCHEMA library of cytokine binding proteins.

Aarthi Rajesh, PhD (Pathology)
Project: Langerhans cells and skin repair.

Ashley Holland, MSc, (Pathology)
Project: Viruses in the placenta and associations with birth complications and future fertility.


Opportunities for Postgraduate Students:

The overarching theme of our research is the use of natural agonists of healing responses to correct impaired healing and scarring impairments. Our research utilises molecular genetics, bioinformatics and biochemistry to identify and produce novel healing agonists. We then utilise cell, 3D skin culture and small animal models, along with histological and molecular analyses, to evaluate potential therapeutics. Projects are available looking at novel therapeutics that regulate inflammation, vascularisation, fibrosis, and nerve and fat regeneration. The group has a strong track record in these areas and the positions will provide the student with excellent opportunities to build their scientific career in these exciting areas.

The University of Otago is one of the top research universities in New Zealand and includes excellent facilities available for our research (e.g. next-generation sequencing, proteomics, histology, microscopy etc.). Our group actively collaborates with other researchers, locally, nationally and internationally. The Department of Pharmacology and Toxicology also has a thriving post-graduate community.

PhD and MSc scholarships are available for talented students interested in studying skin or healing therapeutics. Applicants with a BSc(Hons) or MSc in Molecular Biology, Biochemistry, Genetics, Physiology, Pharmacology or a related discipline and high motivation for research are encouraged to apply. If interested, please contact Dr Lyn Wise providing an explanation of your interest in the project, a CV and details of 2-3 academic referees (lyn.wise@otago.ac.nz). Please include a copy of your full academic transcript and if applicable an explanation of content. Starting dates are flexible. Applicants must be eligible for admission to the PhD or MSc programme at the University of Otago and apply for a scholarship (http://www.otago.ac.nz/study/scholarships/index.html). A GPA of 7.5 or greater and demonstration of proficiency in English are essential.

Publications

Lateef, Z., Stuart, G., Jones, N., Mercer, A., Fleming, S., & Wise, L. (2019). The cutaneous inflammatory response to thermal burn injury in a murine model. International Journal of Molecular Sciences, 20(3), 538. doi: 10.3390/ijms20030538

Sharif, S., Ueda, N., Nakatani, Y., Wise, L. M., Clifton, S., Lateef, Z., Mercer, A. A., & Fleming, S. B. (2019). Chemokine-binding proteins encoded by parapoxvirus of red deer of New Zealand display evidence of gene duplication and divergence of ligand specificity. Frontiers in Microbiology, 10, 1421. doi: 10.3389/fmicb.2019.01421

Wise, L. M., Bodaan, C. J., Stuart, G. S., Real, N. C., Lateef, Z., Mercer, A. A., … Theoret, C. L. (2018). Treatment of limb wounds of horses with orf virus IL-10 and VEGF-E accelerates resolution of exuberant granulation tissue, but does not prevent its development. PLoS ONE, 13(5), e0197223. doi: 10.1371/journal.pone.0197223

Wise, L. M., Stuart, G. S., Real, N. C., Fleming, S. B., & Mercer, A. A. (2018). VEGF receptor-2 activation mediated by VEGF-E limits scar tissue formation following cutaneous injury. Advances in Wound Care, 7(8), 283-297. doi: 10.1089/wound.2016.0721

Lateef, Z., & Wise, L. M. (2018). Exploitation of receptor tyrosine kinases by viral-encoded growth factors. Growth Factors, 36(3-4), 118-140. doi: 10.1080/08977194.2018.1520229

Journal - Research Article

Lateef, Z., Stuart, G., Jones, N., Mercer, A., Fleming, S., & Wise, L. (2019). The cutaneous inflammatory response to thermal burn injury in a murine model. International Journal of Molecular Sciences, 20(3), 538. doi: 10.3390/ijms20030538

Sharif, S., Ueda, N., Nakatani, Y., Wise, L. M., Clifton, S., Lateef, Z., Mercer, A. A., & Fleming, S. B. (2019). Chemokine-binding proteins encoded by parapoxvirus of red deer of New Zealand display evidence of gene duplication and divergence of ligand specificity. Frontiers in Microbiology, 10, 1421. doi: 10.3389/fmicb.2019.01421

Wise, L. M., Bodaan, C. J., Stuart, G. S., Real, N. C., Lateef, Z., Mercer, A. A., … Theoret, C. L. (2018). Treatment of limb wounds of horses with orf virus IL-10 and VEGF-E accelerates resolution of exuberant granulation tissue, but does not prevent its development. PLoS ONE, 13(5), e0197223. doi: 10.1371/journal.pone.0197223

Wise, L. M., Stuart, G. S., Real, N. C., Fleming, S. B., & Mercer, A. A. (2018). VEGF receptor-2 activation mediated by VEGF-E limits scar tissue formation following cutaneous injury. Advances in Wound Care, 7(8), 283-297. doi: 10.1089/wound.2016.0721

Fleming, S. B., McCaughan, C., Lateef, Z., Dunn, A., Wise, L. M., Real, N. C., & Mercer, A. A. (2017). Deletion of the chemokine binding protein gene from the Parapoxvirus Orf virus reduces virulence and pathogenesis in sheep. Frontiers in Microbiology, 8, 46. doi: 10.3389/fmicb.2017.00046

Sharif, S., Nakatani, Y., Wise, L., Corbett, M., Real, N. C., Stuart, G. S., Lateef, Z., Krause, K., Mercer, A. A., & Fleming, S. B. (2016). A broad-spectrum chemokine-binding protein of bovine papular stomatitis virus inhibits neutrophil and monocyte infiltration in inflammatory and wound models of mouse skin. PLoS ONE, 11(12), e0168007. doi: 10.1371/journal.pone.0168007

Bodaan, C. J., Wise, L. M., Wakelin, K. A., Stuart, G. S., Real, N. C., Mercer, A. A., … Theoret, C. (2016). Short-term treatment of equine wounds with orf virus IL-10 and VEGF-E dampens inflammation and promotes repair processes without accelerating closure. Wound Repair & Regeneration, 24(6), 966-980. doi: 10.1111/wrr.12488

Bennett, J. R., Lateef, Z., Fleming, S. B., Mercer, A. A., & Wise, L. M. (2016). Orf virus IL-10 reduces monocyte, dendritic cell and mast cell recruitment to inflamed skin. Virus Research, 213, 230-237. doi: 10.1016/j.virusres.2015.12.015

Wakelin, K. A., Wise, L. M., Bodaan, C. J., Mercer, A. A., Riley, C. B., & Theoret, C. L. (2016). Orf virus interleukin-10 and vascular endothelial growth factor-E modulate gene expression in cultured equine dermal fibroblasts. Veterinary Determatology, 27(5), 434-438. doi: 10.1111/vde.12370

Fleming, S. B., Wise, L. M., & Mercer, A. A. (2015). Molecular genetic analysis of Orf virus: A poxvirus that has adapted to skin. Viruses, 7(3), 1505-1539. doi: 10.3390/v7031505

Lee, S., Chu, H. X., Kim, H. A., Real, N. C., Sharif, S., Fleming, S. B., Mercer, A. A., Wise, L. M., … Sobey, C. G. (2015). Effect of a broad-specificity chemokine-binding protein on brain leukocyte infiltration and infarct development. Stroke, 46, 537-544. doi: 10.1161/strokeaha.114.007298

Couñago, R. M., Knapp, K. M., Nakatani, Y., Fleming, S. B., Corbett, M., Wise, L. M., Mercer, A. A., & Krause, K. L. (2015). Structures of orf virus chemokine binding protein in complex with host chemokines reveal clues to broad binding specificity. Structure, 23(7), 1199-1213. doi: 10.1016/j.str.2015.04.023

Harvey, R., McCaughan, C., Wise, L. M., Mercer, A. A., & Fleming, S. B. (2015). Orf virus inhibits interferon stimulated gene expression and modulates the JAK/STAT signalling pathway. Virus Research, 208, 180-188. doi: 10.1016/j.virusres.2015.06.014

Wise, L. M., Stuart, G. S., Real, N. C., Fleming, S. B., & Mercer, A. A. (2014). Orf virus IL-10 accelerates wound healing while limiting inflammation and scarring. Wound Repair & Regeneration, 22(3), 356-367. doi: 10.1111/wrr.12169

Wise, L. M., Inder, M. K., Real, N. C., Stuart, G. S., Fleming, S. B., & Mercer, A. A. (2012). The vascular endothelial growth factor (VEGF)-E encoded by orf virus regulates keratinocyte proliferation and migration and promotes epidermal regeneration. Cellular Microbiology, 14(9), 1376-1390. doi: 10.1111/j.1462-5822.2012.01802.x

Lateef, Z., Baird, M. A., Wise, L. M., Young, S., Mercer, A. A., & Fleming, S. B. (2010). The chemokine binding protein encoded by the poxvirus orf virus inhibits recruitment of dendritic cells to sites of skin inflammation and migration to peripheral lymph nodes. Cellular Microbiology, 12(5), 665-676. doi: 10.1111/j.1462-5822.2009.01425.x

Lateef, Z., Baird, M. A., Wise, L. M., Mercer, A. A., & Fleming, S. B. (2009). Orf virus-encoded chemokine-binding protein is a potent inhibitor of inflammatory monocyte recruitment in a mouse skin model. Journal of General Virology, 90(6), 1477-1482. doi: 10.1099/vir.0.009589-0

Deane, D., Ueda, N., Wise, L. M., Wood, A. R., Percival, A., Jepson, C., … Fleming, S. B., Mercer, A. A., & McInnes, C. J. (2009). Conservation and variation of the parapoxvirus GM-CSF-inhibitory factor (GIF) proteins. Journal of General Virology, 90, 970-977. doi: 10.1099/vir.0.006692-0

Inder, M. K., Wise, L. M., Fleming, S. B., & Mercer, A. A. (2008). The C-terminus of viral vascular endothelial growth factor-E partially blocks binding to VEGF receptor-1. FEBS Journal, 275(1), 207-217. doi: 10.1111/j.1742-4658.2007.06189.x

Wise, L. M., Savory, L. J., Dryden, N. H., Whelan, E. M., Fleming, S. B., & Mercer, A. A. (2007). Major amino acid sequence variants of viral vascular endothelial growth factor are functionally equivalent during Orf virus infection of sheep skin. Virus Research, 128, 115-125.

Inder, M. K., Ueda, N., Mercer, A. A., Fleming, S. B., & Wise, L. M. (2007). Bovine papular stomatitis virus encodes a functionally distinct VEGF that binds both VEGFR-1 and VEGFR-2. Journal of General Virology, 88, 781-791.

Wise, L., McCaughan, C., Tan, C. K., Mercer, A. A., & Fleming, S. B. (2007). Orf virus interleukin-10 inhibits cytokine synthesis in activated human THP-1 monocytes, but only partially impairs their proliferation. Journal of General Virology, 88, 1677-1682.

Ueda, N., Inder, M. K., Wise, L. M., Fleming, S. B., & Mercer, A. A. (2007). Parapoxvirus of red deer in New Zealand encodes a variant of viral vascular endothelial growth factor. Virus Research, 124, 50-58.

Wise, L., Ueda, N., Dryden, N. H., Fleming, S. B., Caesar, C., Roufail, S., … Mercer, A. A. (2003). Viral vascular endothelial growth factors vary extensively in amino acid sequence, receptor-binding specificities, and the ability to induce vascular permeability yet are uniformly active mitogens. Journal of Biological Chemistry, 278(39), 38004-38014.

Ueda, N., Wise, L., Stacker, S. A., Fleming, S. B., & Mercer, A. A. (2003). Pseudocowpox virus encodes a homolog of vascular endothelial growth factor. Virology, 305, 298-309.

Mercer, A. A., Wise, L. M., Scagliarini, A., McInnes, C. J., Buttner, M., Rziha, H. J., McCaughan, C. A., Fleming, S. B., Ueda, N., & Nettleton, P. F. (2002). Vascular endothelial growth factors encoded by orf virus show surprising sequence variation but have a conserved, functionally relevant structure. Journal of General Virology, 83, 2845-2855.

Makinen, T., Veikkola, T., Mustjoki, S., Karpanen, T., Catimel, B., Nice, E., Wise, L. M., Mercer, A. A., … Alitalo, K. (2001). Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO Journal, 20(17), 4762-4773.

Fleming, S. B., Haig, D. M., Nettleton, P., Reid, H. W., McCaughan, C. A., Wise, L. M., & Mercer, A. (2000). Sequence and functional analysis of a homolog of interleukin-10 encoded by the parapoxvirus orf virus. Virus Genes, 21(1-2), 85-95.

Fleming, S. B., Haig, D. M., Nettleton, P. F., Reid, H. W., McCaughlan, C. A., Wise, L. M., & Mercer, A. A. (2000). Sequence and functional analysis of a homolog of interleukin-10 encoded by the parapoxvirus, orf virus. Virus Genes, 21(1/2), 85-90.

Wise, L. M., Veikkola, T., Mercer, A. A., Savory, L. J., Fleming, S. B., Caesar, C., … Stacker, S. A. (1999). Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1. PNAS, 96(6), 3071-3076. doi: 10.1073/pnas.96.6.3071

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Journal - Research Other

Lateef, Z., & Wise, L. M. (2018). Exploitation of receptor tyrosine kinases by viral-encoded growth factors. Growth Factors, 36(3-4), 118-140. doi: 10.1080/08977194.2018.1520229

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