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Otago Medical School staff profiles

Dr Paul Hessian

PositionSenior Research Fellow
DepartmentDepartment of Medicine (DSM)
QualificationsBSc(Hons) PhD(Otago)
Research summaryMacrophages and adhesion molecules in inflammation

Research

Research in the Leukocyte and Inflammation Research Laboratory focuses on human inflammation biology. The laboratory uses a range of specialist research techniques that span the broad topics of cell biology, biochemistry and molecular biology.

The rheumatoid nodule appears in rheumatoid arthritis patients with the worst disease. Found in subcutaneous sites, and also on the lungs and heart valves, a nodule is a granulomatous lesion, typified by a necrotic centre that is surrounded by a palisading layer of inflammatory monocyte/macrophages. T-lymphocytes and dendritic cells are also present. We have compared this lesion with the joint synovial lesion more commonly associated with RA. The range of proinflammatory and chemotactic cytokines within each lesion is remarkably similar as are the cell populations with the exception that B-lymphocytes are present in inflamed synovium but not the nodule lesion.

We are continuing to characterise the inflammatory milieu of the rheumatoid lesions and have recently expanded the scope of this approach using microarray analysis. Of particular interest are the immune/inflammatory components that initiate and maintain the formation of ectopic lymphoid follicles in the joint synovium. These follicles reflect the presence of follicular dendritic cells (FDC) within the joint. The FDC, even in early stages of follicle development, may provide an indication of the potential for joint damage in patients with early RA. Follicles do not occur in rheumatoid nodules. Follicles and there influence on outcome of rheumatoid arthritis is a topic of research recently funded by the Health Research Council of New Zealand.

The S100 calcium-binding proteins have been implicated as important to a number of inflammatory situations. We continue to work on two members of this family, named S100A8 (or MRP-8) and S100A9 (MRP-14). These two proteins form a heterodimeric complex present in large amounts in the cytosol of monocytes and neutrophils. In human systems, separated S100A9 activates the integrin adhesion molecule, Mac-1, a function consistent with a role for the S100 proteins in inflammation. Current work focuses on how S100A8 and S100A9 mediate any biological effect and particularly the role of RAGE (receptor for advanced glycation end products) as a possible receptor. Detailed analysis of the N-linked glycosylation pattern of RAGE and of modifications to the carbohydratecould provide clues as to how this ligand-receptor axis operates in inflammation.

Publications

McKelvey, K. J., Millier, M. J., Doyle, T. C., Stamp, L. K., Highton, J., & Hessian, P. A. (2018). Co-expression of CD21L and IL17A defines a subset of rheumatoid synovia, characterised by large lymphoid aggregates and high inflammation. PLoS ONE, 13(8), e0202135. doi: 10.1371/journal.pone.0202135

Eason, C. T., Adams, S. L., Puddick, J., Romanazzi, D., Miller, M. R., King, N., … Hessian, P. A., Stamp, L. K., & Packer, M. A. (2018). Greenshell™ mussels: A review of veterinary trials and future research directions. Veterinary Sciences, 5(2), 36. doi: 10.3390/vetsci5020036

Houlder, E. L., Millier, M. J., Highton, J., Gwynne-Jones, D., Stamp, L. K., & Hessian, P. A. (2017). Expression of the genes facilitating methotrexate action within subcutaneous rheumatoid nodules. Clinical & Experimental Rheumatology, 35(6), 943-947.

Millier, M. J., Stamp, L. K., & Hessian, P. A. (2017). Digital-PCR for gene expression: Impact from inherent tissue RNA degradation. Scientific Reports, 7, 17235 . doi: 10.1038/s41598-017-17619-0

Denison, J., Pringle, R., Cassidy, T., & Hessian, P. (2015). Informing coaches' practices: Towards an application of Foucault's ethics. International Sport Coaching Journal, 2(1), 72-76. doi: 10.1123/iscj.2014-0147

Journal - Research Article

McKelvey, K. J., Millier, M. J., Doyle, T. C., Stamp, L. K., Highton, J., & Hessian, P. A. (2018). Co-expression of CD21L and IL17A defines a subset of rheumatoid synovia, characterised by large lymphoid aggregates and high inflammation. PLoS ONE, 13(8), e0202135. doi: 10.1371/journal.pone.0202135

Houlder, E. L., Millier, M. J., Highton, J., Gwynne-Jones, D., Stamp, L. K., & Hessian, P. A. (2017). Expression of the genes facilitating methotrexate action within subcutaneous rheumatoid nodules. Clinical & Experimental Rheumatology, 35(6), 943-947.

Millier, M. J., Stamp, L. K., & Hessian, P. A. (2017). Digital-PCR for gene expression: Impact from inherent tissue RNA degradation. Scientific Reports, 7, 17235 . doi: 10.1038/s41598-017-17619-0

Denison, J., Pringle, R., Cassidy, T., & Hessian, P. (2015). Informing coaches' practices: Towards an application of Foucault's ethics. International Sport Coaching Journal, 2(1), 72-76. doi: 10.1123/iscj.2014-0147

Stamp, L. K., Hazlett, J., Highton, J., & Hessian, P. A. (2013). Expression of methotrexate transporters and metabolizing enzymes in rheumatoid synovial tissue. Journal of Rheumatology, 40(9), 1519-1522. doi: 10.3899/jrheum.130066

Kazantseva, M. G., Hung, N. A., Highton, J., & Hessian, P. A. (2013). MMP expression in rheumatoid inflammation: The rs11568818 polymorphism is associated with MMP-7 expression at an extra-articular site. Genes & Immunity, 14(3), 162-169. doi: 10.1038/gene.2012.65

Kazantseva, M. G., Highton, J., Stamp, L. K., & Hessian, P. A. (2012). Dendritic cells provide a potential link between smoking and inflammation in rheumatoid arthritis. Arthritis Research & Therapy, 14, R208. doi: 10.1186/ar4046

Hazlett, J., Stamp, L. K., Merriman, T., Highton, J., & Hessian, P. A. (2012). IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis. Genes & Immunity, 13, 282-287. doi: 10.1038/gene.2011.80

Stamp, L. K., Hazlett, J., Roberts, R. L., Frampton, C., Highton, J., & Hessian, P. A. (2012). Adenosine receptor expression in rheumatoid synovium: A basis for methotrexate action. Arthritis Research & Therapy, 14, R138. doi: 10.1186/ar3871

Park, S. J., Kleffmann, T., & Hessian, P. A. (2011). The G82S polymorphism promotes glycosylation of the receptor for advanced glycation end products (RAGE) at Asn81: A comparison of wild-type RAGE with the G82S polymorphic variant. Journal of Biological Chemistry, 286(24), 21384-21392. doi: 10.1074/jbc.M111.241281

McKelvey, K. J., Highton, J., & Hessian, P. A. (2011). Cell-specific expression of TLR9 isoforms in inflammation. Journal of Autoimmunity, 36(1), 76-86. doi: 10.1016/j.jaut.2010.11.001

Sutherland, W. H. F., de Jong, S. A., Hessian, P. A., & Williams, M. J. A. (2010). Ingestion of native and thermally oxidized polyunsaturated fats acutely increases circulating numbers of endothelial microparticles. Metabolism, 59(3), 446-453. doi: 10.1016/j.metabol.2009.07.033

Stamp, L. K., Easson, A., Pettersson, L., Highton, J., & Hessian, P. A. (2009). Monocyte derived interleukin (IL)-23 is an important determinant of synovial IL-17A expression in rheumatoid arthritis. Journal of Rheumatology, 36(11), 2403-2408. doi: 10.3899/jrheum.081304

Stamp, L. K., Easson, A., Lehnigk, U., Highton, J., & Hessian, P. A. (2008). Different T cell subsets in the nodule and synovial membrane: Absence of interleukin-17A in rheumatoid nodules. Arthritis & Rheumatism, 58(6), 1601-1608. doi: 10.1002/art.23455

Highton, J., Hung, N., Hessian, P., & Wilsher, M. (2007). Pulmonary rheumatoid nodules demonstrating features usually associated with rheumatoid synovial membrane. Rheumatology, 46, 811-814.

Adams, S. L., Hessian, P. A., & Mladenov, P. (2006). The potential for cryopreserving larvae of the sea urchin, Evechinus chloroticus. Cryobiology, 52, 139-145.

Quinn, M. C. J., McGregor, S. B., Stanton, J. L., Hessian, P. A., Gillett, W. R., & Green, D. P. L. (2006). Purification of granulosa cells from human ovarian follicular fluid using granulosa cell aggregates. Reproduction, Fertility & Development, 18, 501-508.

Adams, S. L., Hessian, P. A., & Mladenov, P. V. (2004). Cryopreservation of sea urchin (Evechinus chloroticus) sperm. CryoLetters, 25, 287-299.

Mabuchi, A., Mullaney, I., Sheard, P. W., Hessian, P. A., Mallard, B. L., Tawadrous, M. N., … Wheatley, A. M. (2004). Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat. Journal of Hepatology, 40, 910-916.

Mabuchi, A., Mullaney, I., Sheard, P., Hessian, P., Zimmermann, A., Senoo, H., & Wheatley, A. M. (2004). Role of hepatic stellate cells in the early phase of liver regeneration in rat: Formation of tight adhesion to parenchymal cells. Comparative Hepatology, 3(Suppl. 1), S29.

Adams, S., Kleinhans, F. W., Mladenov, P., & Hessian, P. A. (2003). Membrane permeability characteristics and osmotic tolerance limits of sea urchin (Evechinus chloroticus) eggs. Cryobiology, 47, 1-13.

Highton, J., Hessian, P. A., Kean, A., & Chin, M. J. (2003). Cell death by apoptosis is a feature of the rheumatoid nodule. Annals of the Rheumatic Diseases, 62, 77-80.

Adams, S., Hessian, P. A., & Mladenov, P. (2003). Flow cytometric evaluation of mitochondrial function and membrane integrity of marine invertebrate sperm. Invertebrate Reproduction & Development, 44(1), 45-51.

Hessian, P. A., Highton, J., Kean, A., Sun, C. K., & Chin, M. J. (2003). Cytokine profile of the rheumatoid nodule suggests that it is a Th1 granuloma. Arthritis & Rheumatism, 48(2), 334-338.

Hessian, P. A., & Fisher, L. (2001). The heterodimeric complex of MRP-8 (S100A8) and MRP-14 (S100A9), antibody recognition, epitope definition and the implications for structure. European Journal of Biochemistry, 268, 353-363.

Highton, J., Kean, A., Hessian, P. A., Thomson, J., Rietveld, J., & Hart, D. N. (2000). Cells expressing dendritic cell markers are present in the rheumatoid nodule. Journal of Rheumatology, 27(2), 339-346.

Wikaningrum, R., Highton, J., Smith, M., Parker, A., Coleman, M., Roberts-Thomson, P. J., Hessian, P. A., & Ahern, M. J. (1998). Pathogenic mechanisms in the rheumatoid nodule: comparison of pro-inflammatory cytokine production and cell adhesion molecule expression in rheumatoid nodules and synovial membranes from the same patient. Arthritis & Rheumatism, 41, 1783-1797.

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Journal - Research Other

Eason, C. T., Adams, S. L., Puddick, J., Romanazzi, D., Miller, M. R., King, N., … Hessian, P. A., Stamp, L. K., & Packer, M. A. (2018). Greenshell™ mussels: A review of veterinary trials and future research directions. Veterinary Sciences, 5(2), 36. doi: 10.3390/vetsci5020036

Highton, J., Hessian, P. A., & Stamp, L. (2007). The rheumatoid nodule: Peripheral or central to rheumatoid arthritis? [Editorial]. Rheumatology, 46, 1385-1387.

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