Skip to the content
 

Monash Centre for Inflammatory Diseases

Professor Stephen Holdsworth - Director of Centre

Professor Stephen Holdsworth

Professor Stephen Holdsworth is the Director of the Centre for Inflammatory Diseases, Head of the Department of Medicine (Monash Medical Centre) and Head of the Southern Clinical School, Monash University.  He also holds several positions at Southern Health including Director of Clinical and Diagnostic Immunology, Director Research Strategy, Chair of the Senior Medical Staff Association and Consultant Nephrologist.

Professor Holdsworth is a clinician-scientist who is a nephrologist, clinical immunologist and career academic. His long-standing research interests have focussed on the mechanisms in immune glomerular injury relevant to understanding and treating human glomerulonephritis (GN). His work has substantially contributed to revelations that cell-mediated immunity and pathological coagulation induce crescentic GN. The evidence substantiating this assertion derives from key in vivo studies in animals models bracketed with human observations confirming the relevance of experimental discoveries to human disease.

In 2005, Professor Holdsworth received the Kincaid Smith Medal, the highest accolade given in Australia for excellence in contributing to Nephrology. He served as Head of the NHMRC Program Grant Committee 1997-1999 and is currently CIA on three NHMRC Project Grants.

Publications

Journal Articles

  1. Summers SA, van der Veen BS, O'Sullivan KM, Gan PY, Ooi JD, Heeringa P, Satchell SC, Mathieson PW, Saleem MA, Visvanathan K, Holdsworth SR, Kitching AR. Intrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis. Kidney Int. 2010 Dec;78(12):1263-74.
  2. Summers SA, Steinmetz OM, Gan PY, Ooi JD, Odobasic D, Kitching A, Holdsworth SR. TLR2 induces Th17 myeloperoxidase autoimmunity, while TLR9 drives Th1 autoimmunity. Arthritis Rheum. 2010 Dec 28.
  3. Summers SA, Hoi A, Steinmetz OM, O'Sullivan KM, Ooi JD, Odobasic D, Akira S, Kitching AR, Holdsworth SR. TLR9 and TLR4 are required for the development of autoimmunity and lupus nephritis in pristane nephropathy. J Autoimmun. 2010 Dec;35(4):291-8.
  4. Steinmetz OM, Summers SA, Gan PY, Semple T, Holdsworth SR, Kitching AR. The Th17-Defining Transcription Factor ROR{gamma}t Promotes Glomerulonephritis. J Am Soc Nephrol. 2010 Dec 23.
  5. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Farmer MW, Guy P, Holmes PW. Lung diffusing capacity in adult bronchiectasis: a longitudinal study. Respir Care. 2010 Dec;55(12):1686-92.
  6. Summers SA, Steinmetz OM, Ooi JD, Gan PY, O'Sullivan KM, Visvanathan K, Akira S, Kitching AR, Holdsworth SR. Toll-like receptor 9 enhances nephritogenic immunity and glomerular leukocyte recruitment, exacerbating experimental crescentic glomerulonephritis. Am J Pathol. 2010 Nov;177(5):2234-44.
  7. Ooi JD, Kitching AR, Holdsworth SR. Review. T helper 17 cells: their role in glomerulonephritis. Nephrology (Carlton). 2010; 15(5):513-21
  8. Gan PY, Steinmetz OM, Tan DS, O'Sullivan KM, Ooi JD, Iwakura Y, Kitching AR, Holdsworth SR. Th17 cells promote autoimmune anti-myeloperoxidase glomerulonephritis. J Am Soc Nephrol. 2010 June;21(6):925-31
  9. Summers SA, Steinmetz OM, Li M, Kausman JY, Semple T, Edgtton KL, Borza DB, Braley H, Holdsworth SR, Kitching AR. Th1 and Th17 cells induce proliferative glomerulonephritis. J Am Soc Nephrol. 2009 Dec;20(12):2518-24. Epub 2009 Oct 9. 
  10. Phoon RK, Kitching AR, Jones LK, Holdsworth SR. Atorvastatin enhances humoral immune responses but does not alter renal injury in experimental crescentic glomerulonephritis. Nephrology (Carlton). 2009 Oct;14(7):650-7. 
  11. Li M, O'Sullivan KM, Jones LK, Lo C, Semple T, Kumanogoh A, Kikutani H, Holdsworth SR, Kitching R. Endogenous CD100 promotes glomerular injury and macrophage recruitment in experimental crescentic glomerulonephritis. Immunology. 2009 Sep;128(1):114-22.
  12. Jones LK, O'Sullivan KM, Semple T, Kuligowski MP, Fukami K, Ma FY, Nikolic-Paterson DJ, Holdsworth SR, Kitching AR. IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis. Nephrol Dial Transplant. 2009 Oct;24(10):3024-32. Epub 2009 May 22.
  13. King PT, Holdsworth SR, Farmer M, Freezer N, Villanueva E, Holmes PW. Phenotypes of adult bronchiectasis: onset of productive cough in childhood and adulthood. COPD. 2009 Apr;6(2):130-6.
  14. Ooi JD, Phoon RK, Holdsworth SR, Kitching AR. IL-23, not IL-12, directs autoimmunity to the Goodpasture antigen. J Am Soc Nephrol. 2009 May;20(5):980-9. Epub 2009 Apr 8.
  15. Holdsworth SR, Summers SA. Role of mast cells in progressive renal diseases. J Am Soc Nephrol. 2008 Dec;19(12):2254-61. Epub 2008 Sep 5. Review.
  16. Summers S, Holdsworth S, Sharples E: The (re)challenging question of erythropoiesis-stimulating agents inducing pure red cell aplasia. Nephrol Dial Transplant 2008;23:3053-3055.
  17. Phoon RK, Kitching AR, Odobasic D, Jones LK, Semple TJ, Holdsworth SR: T-bet deficiency attenuates renal injury in experimental crescentic glomerulonephritis. J Am Soc Nephrol 2008;19:477-485.
  18. Ooi JD, Holdsworth SR, Kitching AR: Advances in the pathogenesis of goodpasture's disease: From epitopes to autoantibodies to effector t cells. J Autoimmun 2008
  19. Odobasic D, Leech MT, Xue JR, Holdsworth SR: Distinct in vivo roles of cd80 and cd86 in the effector t-cell responses inducing antigen-induced arthritis. Immunology 2008;124:503-513.
  20. Kitching AR, Holdsworth SR, Hickey MJ: Targeting leukocytes in immune glomerular diseases. Curr Med Chem 2008;15:448-458.
  21. King PT, Ngui J, Gunawardena D, Holmes PW, Farmer MW, Holdsworth SR: Systemic humoral immunity to non-typeable haemophilus influenzae. Clin Exp Immunol 2008;153:376-384.
  22. King PT, Ngui J, Farmer MW, Hutchinson P, Holmes PW, Holdsworth SR: Cytotoxic t lymphocyte and natural killer cell responses to non-typeable haemophilus influenzae. Clin Exp Immunol 2008;152:542-551.
  23. Holdsworth SR, Summers SA: Role of mast cells in progressive renal diseases. J Am Soc Nephrol 2008
  24. Edgtton KL, Kausman JY, Li M, O'Sullivan K, Lo C, Hutchinson P, Yagita H, Holdsworth SR, Kitching AR: Intrarenal antigens activate cd4+ cells via co-stimulatory signals from dendritic cells. J Am Soc Nephrol 2008;19:515-526.
  25. Tipping PG, Holdsworth SR: Cytokines in glomerulonephritis. Semin Nephrol 2007;27:275-285.
  26. Odobasic D, Kitching AR, Semple TJ, Holdsworth SR: Endogenous myeloperoxidase promotes neutrophil-mediated renal injury, but attenuates t cell immunity inducing crescentic glomerulonephritis. J Am Soc Nephrol 2007;18:760-770.
  27. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW: Microbiologic follow-up study in adult bronchiectasis. Respir Med 2007;101:1633-1638.
  28. Holdsworth SR, Tipping PG: Leukocytes in glomerular injury. Semin Immunopathol 2007;29:355-374.
  29. Tipping PG, Holdsworth SR: T cells in crescentic glomerulonephritis. J Am Soc Nephrol 2006;17:1253-1263.
  30. Timoshanko JR, Kitching R, Semple TJ, Tipping PG, Holdsworth SR: A pathogenetic role for mast cells in experimental crescentic glomerulonephritis. J Am Soc Nephrol 2006;17:150-159.
  31. Ruth AJ, Kitching AR, Kwan RY, Odobasic D, Ooi JD, Timoshanko JR, Hickey MJ, Holdsworth SR: Anti-neutrophil cytoplasmic antibodies and effector CD4+ cells play nonredundant roles in anti-myeloperoxidase crescentic glomerulonephritis. J Am Soc Nephrol 2006;17:1940-1949.
  32. Odobasic D, Kitching AR, Semple TJ, Holdsworth SR: Inducible co-stimulatory molecule ligand is protective during the induction and effector phases of crescentic glomerulonephritis. J Am Soc Nephrol 2006;17:1044-1053.
  33. Li M, O'Sullivan KM, Jones LK, Semple T, Kumanogoh A, Kikutani H, Holdsworth SR, Kitching AR: Cd100 enhances dendritic cell and cd4+ cell activation leading to pathogenetic humoral responses and immune complex glomerulonephritis. J Immunol 2006;177:3406-3412.
  34. King PT, Hutchinson P, Holmes PW, Freezer NJ, Bennett-Wood V, Robins-Browne R, Holdsworth SR: Assessing immune function in adult bronchiectasis. Clin Exp Immunol 2006;144:440-446.
  35. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW: Characterisation of the onset and presenting clinical features of adult bronchiectasis. Respir Med 2006;100:2183-2189.
  36. Apostolopoulos J, Ooi JD, Odobasic D, Holdsworth SR, Kitching AR: The isolation and purification of biologically active recombinant and native autoantigens for the study of autoimmune disease. J Immunol Methods 2006;308:167-178.
  37. Timoshanko JR, Kitching AR, Semple TJ, Holdsworth SR, Tipping PG: Granulocyte macrophage colony-stimulating factor expression by both renal parenchymal and immune cells mediates murine crescentic glomerulonephritis. J Am Soc Nephrol 2005;16:2646-2656.
  38. Odobasic D, Kitching AR, Tipping PG, Holdsworth SR: Cd80 and cd86 costimulatory molecules regulate crescentic glomerulonephritis by different mechanisms. Kidney Int 2005;68:584-594.
  39. Odobasic D, Kitching AR, Semple TJ, Timoshanko JR, Tipping PG, Holdsworth SR: Glomerular expression of cd80 and cd86 is required for leukocyte accumulation and injury in crescentic glomerulonephritis. J Am Soc Nephrol 2005;16:2012-2022.
  40. Kitching AR, Turner AL, Wilson GR, Semple T, Odobasic D, Timoshanko JR, O'Sullivan KM, Tipping PG, Takeda K, Akira S, Holdsworth SR: Il-12p40 and il-18 in crescentic glomerulonephritis: Il-12p40 is the key th1-defining cytokine chain, whereas il-18 promotes local inflammation and leukocyte recruitment. J Am Soc Nephrol 2005;16:2023-2033.
  41. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Gallagher M, Holmes PW: Outcome in adult bronchiectasis. COPD 2005;2:27-34.
  42. Hughes AJ, Hutchinson P, Gooding T, Freezer NJ, Holdsworth SR, Johnson PD: Diagnosis of mycobacterium tuberculosis infection using esat-6 and intracellular cytokine cytometry. Clin Exp Immunol 2005;142:132-139.
  43. Dean EG, Wilson GR, Li M, Edgtton KL, O'Sullivan KM, Hudson BG, Holdsworth SR, Kitching AR: Experimental autoimmune goodpasture's disease: A pathogenetic role for both effector cells and antibody in injury. Kidney Int 2005;67:566-575.
  44. Blazik M, Hutchinson P, Jose MD, Polkinghorne KR, Holdsworth SR, Atkins RC, Chadban SJ: Leukocyte phenotype and function predicts infection risk in renal transplant recipients. Nephrol Dial Transplant 2005;20:2226-2230.
  45. Timoshanko JR, Kitching AR, Iwakura Y, Holdsworth SR, Tipping PG: Contributions of il-1beta and il-1alpha to crescentic glomerulonephritis in mice. J Am Soc Nephrol 2004;15:910-918.
  46. Timoshanko JR, Kitching AR, Iwakura Y, Holdsworth SR, Tipping PG: Leukocyte-derived interleukin-1beta interacts with renal interleukin-1 receptor i to promote renal tumor necrosis factor and glomerular injury in murine crescentic glomerulonephritis. Am J Pathol 2004;164:1967-1977.
  47. Ruth AJ, Kitching AR, Li M, Semple TJ, Timoshanko JR, Tipping PG, Holdsworth SR: An il-12-independent role for cd40-cd154 in mediating effector responses: Studies in cell-mediated glomerulonephritis and dermal delayed-type hypersensitivity. J Immunol 2004;173:136-144.
  48. Kitching AR, Turner AL, Wilson GR, Edgtton KL, Tipping PG, Holdsworth SR: Endogenous il-13 limits humoral responses and injury in experimental glomerulonephritis but does not regulate th1 cell-mediated crescentic glomerulonephritis. J Am Soc Nephrol 2004;15:2373-2382.
  49. Kitching AR, Turner AL, Semple T, Li M, Edgtton KL, Wilson GR, Timoshanko JR, Hudson BG, Holdsworth SR: Experimental autoimmune anti-glomerular basement membrane glomerulonephritis: A protective role for ifn-gamma. J Am Soc Nephrol 2004;15:1764-1774.
  50. Kitching AR, Hutchinson P, Atkins RC, Holdsworth SR: The role of flow cytometric anca detection in screening for acute pauci-immune crescentic glomerulonephritis. Nephrol Dial Transplant 2004;19:365-370.
  51. King PT, Freezer NJ, Holmes PW, Holdsworth SR, Forshaw K, Sart DD: Role of cftr mutations in adult bronchiectasis. Thorax 2004;59:357-358.
  52. Hutchinson P, Jose M, Atkins RC, Holdsworth SR: Ex vivo lymphocyte proliferative function is severely inhibited in renal transplant patients on mycophenolate mofetil treatment. Transpl Immunol 2004;13:55-61.
  53. Cunningham MA, Kitching AR, Tipping PG, Holdsworth SR: Fibrin independent proinflammatory effects of tissue factor in experimental crescentic glomerulonephritis. Kidney Int 2004;66:647-654.
  54. Tipping PG, Holdsworth SR: T cells in glomerulonephritis. Springer Semin Immunopathol 2003;24:377-393.
  55. Timoshanko JR, Sedgwick JD, Holdsworth SR, Tipping PG: Intrinsic renal cells are the major source of tumor necrosis factor contributing to renal injury in murine crescentic glomerulonephritis. J Am Soc Nephrol 2003;14:1785-1793.
  56. Ruth AJ, Kitching AR, Semple TJ, Tipping PG, Holdsworth SR: Intrinsic renal cell expression of cd40 directs th1 effectors inducing experimental crescentic glomerulonephritis. J Am Soc Nephrol 2003;14:2813-2822.
  57. Kitching AR, Kong YZ, Huang XR, Davenport P, Edgtton KL, Carmeliet P, Holdsworth SR, Tipping PG: Plasminogen activator inhibitor-1 is a significant determinant of renal injury in experimental crescentic glomerulonephritis. J Am Soc Nephrol 2003;14:1487-1495.
  58. King PT, Hutchinson PE, Johnson PD, Holmes PW, Freezer NJ, Holdsworth SR: Adaptive immunity to nontypeable haemophilus influenzae. Am J Respir Crit Care Med 2003;167:587-592.
  59. Hutchinson P, Chadban SJ, Atkins RC, Holdsworth SR: Laboratory assessment of immune function in renal transplant patients. Nephrol Dial Transplant 2003;18:983-989.

Book Chapter

   1.  Holdsworth SR and Tipping PG.  Pathways of cellular adaptive immunity in autoimmune crescentic glomerulonephritis and lupus nephritis.  2011 Lupus Nephritis 2nd edition  (edited by Lewis EJ, et al). ISBN 978-0-19-956805-5