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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 Monash University's Department of Medicine (Monash Medical Centre), Head of the Southern Clinical School and Head of Clinical Immunology atSouthern Health.

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 an NHMRC Program Grant (2005-2009).

Publications 2002-2008

  1. 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 May 22. [Epub ahead of print]
  2. Kitching AR, Holdsworth SR, Hickey MJ.  Targeting leukocytes in immune glomerular diseases. Curr Med Chem. 2008;15(5):448-58.  
  3. 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 Mar;19(3):477-85. Epub 2008 Jan 30.
  4. 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 Jan 24. [Epub ahead of print]  
  5. 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 Mar;19(3):515-26. Epub 2008 Jan 9.     
  6. 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(3):760-70.  
  7. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW. Microbiologic follow-up study in adult bronchiectasis. Respir Med. 2007;101(8):1633-8.  
  8. 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(1):150-9.  
  9. 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(7):1940-9.
  10. 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(1):150-9.  
  11. 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 Jun;164(6):1967-77.
  12. 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(4):1044-53.   
  13. 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(12):2183-9.  
  14. 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 1;177(5):3406-12.    
  15. 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(3):440-6.    
  16. 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 20;308(1-2):167-78.
  17. 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 20;308(1-2):167-78.  
  18. 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(9):2646-56.
  19. 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(7):2023-33.   
  20. Odobasic D, Kitching AR, Tipping PG, Holdsworth SR. CD80 and CD86 costimulatory molecules regulate crescentic glomerulonephritis by different mechanisms. Kidney Int. 2005;68(2):584-94.  
  21. 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(2):566-75.  
  22. 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(7):2012-22.   
  23. 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(10):2226-30.  
  24. 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(1):132-9.  
  25. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Gallagher M, Holmes PW. Outcome in adult bronchiectasis. COPD. 2005;2(1):27-34.  
  26. 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(9):2373-82.  
  27. 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(7):1764-74.   
  28. 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(4):910-8.   
  29. 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 1;173(1):136-44.  
  30. 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(7):1785-93.     
  31. King PT, Freezer NJ, Holmes PW, Holdsworth SR, Forshaw K, Sart DD. Role of CFTR mutations in adult bronchiectasis. Thorax. 2004;59(4):357-8.   
  32. Cunningham MA, Kitching AR, Tipping PG, Holdsworth SR. Fibrin independent proinflammatory effects of tissue factor in experimental crescentic glomerulonephritis. Kidney Int. 2004;66(2):647-54.
  33. 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(2):365-70. 
  34. 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(1):55-61.
  35. 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(4):587-92. 
  36. 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(7):1785-93.
  37. 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(11):2813-22.
  38. 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(6):1487-95.  
  39. Hutchinson P, Chadban SJ, Atkins RC, Holdsworth SR. Laboratory assessment of immune function in renal transplant patients. Nephrol Dial Transplant. 2003;18(5):983-9.
  40. Kitching AR, Ru Huang X, Turner AL, Tipping PG, Dunn AR, Holdsworth SR. The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in leukocyte-mediated immune glomerular injury. J Am Soc Nephrol. 2002;13(2):350-8.
  41. Timoshanko JR, Holdsworth SR, Kitching AR, Tipping PG. IFN-gamma production by intrinsic renal cells and bone marrow-derived cells is required for full expression of crescentic glomerulonephritis in mice. J Immunol. 2002 15;168(8):4135-41.  
  42. Kitching AR, Katerelos M, Mudge SJ, Tipping PG, Power DA, Holdsworth SR. Interleukin-10 inhibits experimental mesangial proliferative glomerulonephritis. Clin Exp Immunol. 2002;128(1):36-43.
  43. Kitching AR, Huang XR, Ruth AJ, Tipping PG, Holdsworth SR. Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis in BALB/c mice. Clin Exp Immunol. 2002;128(3):429-35.
  44. Nagappan R, Parkin WG, Holdsworth SR. Acute lithium intoxication. Anaesth Intensive Care. 2002;30(1):90-2.

Reviews

  1. Kitching AR, Holdsworth SR, Hickey MJ Targeting Leukocytes in Immune Glomerular Diseases. Current Medicinal Chemistry 2008;15(5):448-58.  
  2. Summers S, Holdsworth S, Sharples E. The (re-)challenging question of erythropoiesis-stimulating agents inducing pure red cell aplasia. Nephrol Dial Transplant. 2008 Jun 16. [Epub ahead of print]  
  3. Ooi J, Holdsworth SR, Kitching AR.  Autoimmune renal disease.  Journal of Autoimmunity 2008 in press.   
  4. Holdsworth SR, Summers S. The role of the mast cell in chronic inflammatory renal diseases. J Am Soc Nephrol (in press 2008)  
  5. Tipping PG, Holdsworth SR. Cytokines in glomerulonephritis. Semin Nephrol. 2007;27(3):275-85.  
  6. Holdsworth SR, Tipping PG.Leukocytes in glomerular injury. Semin Immunopathol. 2007 Nov;29(4):355-74. Epub 2007 Oct 16.
  7. Tipping PG, Holdsworth SR. T cells in crescentic glomerulonephritis. J Am Soc Nephrol. 2006;17(5):1253-63.  
  8. Tipping PG, Holdsworth SR. T cells in glomerulonephritis. Springer Semin Immunopathol. 2003;24(4):377-93.