Dr Nicole Mifsud - Researcher Profile

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Address

The Alfred Centre
99 Commercial Road

Biography

Research interests
1.    HLA and transplant immunology: Examining allogeneic T cell responses in HLA mismatched transplants. Development of a novel cellular assay for allo-specific T cell quantitation to explore HLA alloreactivity and immunodominance hierarchies. Key findings investigating HLA alloreactivity resulted in several publications (AJT, PNAS, Transplantation, Immunity). Investigating both innate and adaptive immunity in lung transplant recipients and the association with long term outcomes. Methodologies include cell culture, cellular assays, transfected cell lines, MHC/peptide tetramers, flow cytometry and molecular techniques.
2.    Cross-reactive anti-viral memory T cells: Exploring the role of known and/or discover novel  cross-reactive anti-viral memory T cells following transplantation. Measuring the contribution of both allo-specific  and virus-specific T cells to the overall alloresponse. To determine whether the presence of cross-reactive anti-viral T cells modulates the alloresponse. Methodologies are same as outlined above. 

Research:
My scientific research career began in Immunohaematology with an interest in red cell antigens. My seminal research led to the development of novel molecular genotyping for ABO (2 first author publications) and KEL (1 first author publication in prestigious journal, Blood) blood group systems and the discovery of 3 new alleles (O, B and cis-AB groups; 1 first author publication) and an ASBT/HSANZ conference award (1998). This work led to numerous local and national invited speaker presentations to special interests groups, education meetings and conferences.
Gaining interest in transplantation immunology, particularly improved transplant donor/recipient matching strategies for better post transplant outcomes, I undertook an Honours (2000) and subsequent PhD (2001-2004) project entitled “Assessing the allogeneic T cell response in transplantation” (supervisor Prof. J. McCluskey, University of Melbourne) to develop a novel cellular assay for quantitation of allo-specific T cells. Key research findings, enabled contribution to 4 team oriented publications (Immunity, J Exp Med, PNAS) and a first author publication (Am J Transplant). Presentation of my research at national and international meetings led to the ASEATTA conference award (2001).
Consolidation of my T cell immunology research interests was achieved with a 2 year postdoctoral position (2004-06) at Ludwig Institute for Cancer Research (supervisor A/Prof W. Chen). I refined technical skills and knowledge in the areas of antigen processing/presentation and identification of novel T cell epitopes from the NY-ESO-1 protein, providing key data for 3 team publications (PNAS, J Immunol).
Shifting my focus back towards human T cell immunology in solid organ (lung) transplantation, I joined the Respiratory Medicine Laboratory (Head, A/Prof T. Kotsimbos) Monash University/Alfred Hospital (2006-current). This postdoctoral and laboratory manager position has enabled me to develop my own scientific interests in a clinical environment; (i) measurement of allo-specific T cells and dissection of the immunodominance hierarchy (Am J Transplant), (ii) heterologous immunity mediated by cross-reactive anti-viral memory T cells (ICB, Transplantation, collaborations: Dr K. Kedzierska, University of Melbourne), (iii) chronic DNA viruses and their contribution to bronchiolitis obliterans syndrome in lung transplantation (Am J Transplant, Transplantation, collaborations: clinicians in the Lung Transplant Unit, Alfred Hospital) and (iii) injury and repair mechanisms following lung transplantation (collaborations: Dr A. Bourdin, CHU Arnaud de Villeneuve, France & Dr J. Jowett, Baker IDI).
The pursuit of cutting edge translational research enabled me to obtain a NHMRC Peter Doherty Fellowship (2007-10) and funding from industry (2006 ARCBS CI-B), philanthropic foundations (2007-08, 2010-12 The Margaret Pratt Foundation CI-A) and a NHMRC project grant (2009-11 CI-B). I peer review for Am J Transplant, J Immunology, Respirology, Clin Exp Allergy, Human Immunology, Tissue Antigens and Int Arch Allergy Immunology.

 

Related Links:

Keywords

HLA, transplantation, immunology, T cells,, anti-tumour immunity; cd8+ t cells; cross-priming; influenza a, cross-reactive viral T cells, alloreactivity, cross-reactivity, t cells, lung transplant recipients, human cytomegalovirus; ie1-pp65 protein; immunodominance hierarchy

Qualifications

MICROBIOLOGY AND IMMUNOLOGY
Institution: Melbourne
Year awarded: 2005
BIOLOGICAL SCIENCES
Institution: La Trobe Uni
Year awarded: 1993

Publications

Book Chapters

Bharadwaj, M., Mifsud, N.A., McCluskey, J., 2012, Detection and characterisation of Alloreactive T cells, in Immunogenetics, eds Frank T Christiansen, Humana Press, London, pp. 309-337.

Journal Articles

Zhao, R.Y., Mifsud, N.A., Xiao, K., Chan, K., Oveissi, S., Jackson, H., Dimopoulos, N., Guillaume, P., Knights, A.J., Lowen, T., Robson, N.C., Russell, S.E., Scotet, E., Davis, I., Maraskovsky, E., Cebon, J., Luescher, I.F., Chen, W., 2012, A novel HLA-B18 restricted CD8+ T cell epitope is efficiently cross-presented by dendritic cells from soluble tumor antigen, PLoS ONE [P], vol 7, issue 9 (Art. No: e44707), Public Library of Science, United States, pp. 1-12.

Bourdin, A., Mifsud, N.A., Chanez, B., McLean, C., Chanez, P., Snell, G.I., Kotsimbos, A.T.C., 2012, Donor clara cell secretory protein polymorphism is a risk factor for bronchiolitis obliterans syndrome after lung transplantation, Transplantation [P], vol 94, issue 6, Lippincott Williams & Wilkins, United States, pp. 652-658.

Carroll, K.E., Dean, M.M., Heatley, S.L., Meehan, A.C., Mifsud, N.A., Kotsimbos, A.T.C., Snell, G.I., Westall, G.P., 2011, High Levels of Mannose-Binding Lectin Are Associated With Poor Outcomes After Lung Transplantation, Transplantation [P], vol 91, issue 9, Lippincott Williams & Wilkins, Inc., United States, pp. 1044-1049.

Carroll, K.E., Dean, M.M., Heatley, S.L., Meehan, A.C., Mifsud, N., Kotsimbos, T.C., Snell, G.I., Westall, G.P., 2011, High levels of mannose-binding lectin are associated with poor outcomes after lung transplantation, Transplantation [P], vol 91, issue 9, Lippincott Williams & Wilkins, USA, pp. 1044-1049.

Nguyen, T.H.O., Sullivan, L.C., Kotsimbos, T.C., Schwarer, A.P., Mifsud, N.A., 2010, Cross-presentation of HCMV chimeric protein enables generation and measurement of polyclonal T cells, Immunology And Cell Biology [P], vol 88, issue 6, Nature Publishing Group, United Kingdom, Australia, pp. 676-684.

Wei, J., Waithman, J., Lata, R., Mifsud, N., Cebon, J., Kay, T., Smyth, M., Sadler, A., Chen, W., 2010, Influenza a infection enhances cross-priming of CD8+ T cells to cell-associated antigens in a TLR7-and type I IFN-dependent fashion, Journal Of Immunology [P], vol 185, issue 10, American Association of Immunologists, USA, pp. 6013-6022.

Meehan, A.C., Sullivan, L.C., Mifsud, N.A., Brooks, A.G., Snell, G.I., Kotsimbos, T.C., Westall, G.P., 2010, Natural killer cell activation in the lung allograft early posttransplantation, Transplantation [P], vol 89, Lippincott Williams & Wilkins, United States, pp. 756-763.

Mifsud, N.A., Nguyen, T., Tait, B.D., Kotsimbos, A., 2010, Quantitative and functional diversity of cross-reactive EBV-specific CD8+ T cells in a longitudinal study cohort of lung transplant recipients, Transplantation [P], vol 90, issue 12, Lippincott Williams & Wilkins, United States, pp. 1439-1449.

Keating, D., Michaelides, A., Mifsud, N., Bowden, S., Kotsimbos, A., 2010, Respiratory epithelium: an unlikely reservoir for latent human polyomavirus infection but a likely portal of entry., Transplantation [P], vol 89, issue 5, Lippincott Williams & Wilkins, United States, Canada, pp. 634-635.

Van der Meulen, J.D., Mifsud, N.A., Abud, D., Paul, E., Varney, M., Lewin, S.R., Cameron, P.U., Kotsimbos, T.C., 2009, Differential dynamics of donor DC and non-DC peripheral blood mononuclear cell microchimerism in lung transplantation, Clinical Immunology [P], vol 133, issue 2, Academic Press, United States, pp. 179-183.

Allen, K.J., Mifsud, N.A., Williamson, R., Bertolino, P., Hardikar, W., 2008, Cell-mediated rejection results in allograft loss after liver cell transplantation, Liver Transplantation, vol 14, issue 5, John Wiley & Sons, United States, pp. 688-694.

Chessman, D., Kostenko, L., Lethborg, T., Purcell, A.W., Williamson, N.A., Chen, Z., Kjer-Nielsen, L., Mifsud, N.A., Tait, B.D., Holdsworth, R., Almeida, C.A., Nolan, D., Macdonald, W.A., Archbold, J.K., Kellerher, A.D., Marriott, D., Mallal, S., Bharadwaj, M., Rossjohn, J., McCluskey, J., 2008, Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity, Immunity, vol 28, issue 6, Cell Press, USA, pp. 822-832.

Mifsud, N.A., Purcell, A.W., Chen, W.W., Holdsworth, R., Tait, B.D., McCluskey, J., 2008, Immunodominance hierarchies and gender bias in direct Tcd8-cell alloreactivity, American Journal of Transplantation, vol 8, issue 1, Wiley-Blackwell Publishing Ltd., United Kingdom, United States, pp. 121-132.

Westall, G.P., Mifsud, N.A., Kotsimbos, T.C., 2008, Linking CMV serostatus to episodes of CMV reactivation following lung transplantation by measuring CMV-specific CD8+ T-cell immunity, American Journal of Transplantation, vol 8, issue 8, Wiley-Blackwell Publishing Ltd., United States, pp. 1749-1754.

Nguyen, T.H.O., Mifsud, N.A., Stewart, L.A., Rose, M.J., Etto, T.L., Williamson, N.A., Purcell, A.W., Kotsimbos, T.C., Schwarer, A., 2008, Refinement in the production and purification of recombinant HCMV IE1-pp65 protein for the generation of epitope-specific T cell immunity, Protein Expression and Purification, vol 61, issue 1, Elsevier, United States, pp. 22-30.

Kjer-Nielsen, L., Dunstone, M.A., Kostenko, L., Ely, L.K., Beddoe, T.C., Mifsud, N.A., Purcell, A.W., Brooks, A.G., McCluskey, J., Rossjohn, J., 2004, Crystal structure of the human T cell receptor CD3 heterodimer complexed to the therapeutic mAb OKT3, Proceeedings of the National Academy of Sciences of the United Stated of America, vol 101, issue 20, National Academy of Sciences, Washington USA, pp. 7675-7680.

Zernich, D., Purcell, A.W., Macdonald, W.A., Kjer-Nielsen, L., Ely, L.K., Laham, N., Crockford, T., Mifsud, N.A., Bharadwaj, M., Chang, L., Tait, B.D., Holdsworth, R., Brooks, A.G., Bottomley, S.P., Beddoe, T.C., Peh, C.A., Rossjohn, J., McCluskey, J., 2004, Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion, The Journal of Experimental Medicine, vol 200, issue 1, Rockerfeller University Press, New York USA, pp. 13-24.

Macdonald, W.A., Purcell, A.W., Mifsud, N.A., Ely, L.K., Williams, D.S., Chang, L., Gorman, J.J., Clements, C.S., Kjer-Nielsen, L., Koelle, D.M., Burrows, S.R., Tait, B.D., Holdsworth, R., Brooks, A.G., Lovrecz, G.O., Lu, L., Rossjohn, J., McCluskey, J., 2003, A naturally selected dimorphism within the HLA-B44 supertype alters Class I structure, peptide repertoire, and T cell recognition, Journal of Experiemental Medicine, vol 198, issue 5, Rockefeller University Press, New York USA, pp. 679-691.

Conference Proceedings

Lee, A., Button, B., Denehy, L., Roberts, S., Bamford, T.L., Mifsud, N.A., Mu, F., Stirling, R.G., Wilson, J.W., 2009, Pepsin, a measure of pulmonary microaspiration in COPD and bronchiectasis, APA Conference Week 2009 Online Abstracts - Cardiorespiratory Physiotherapy Australia, October 1-5, Australian Physiotherapy Association, Australia, p. 13.

Activities

Departmental committees

From: 01/01/0010 To: 01/12/0011
Monash University Central Clinical School
Early Career Researchers Committee
Founder and Chairperson

From: 01/01/0010
Monash University Faculty of Medicine Nursing and Health Science
Early Career Researchers Steering committee
Central Clinical School representative

From: 01/01/2008 To: 12/12/2009
Monash University Central Clinical School
AMREP First floor Laboratory Meetings
Chairperson

From: 01/01/2009 To: 31/12/2010
Monash University Central Clinical School
Equipment Committee
committee member

From: 01/01/2011
Alfred Medical Research and Education Precinct (AMREP)
Early Career Researchers retreat committee
Founder and Chairperson

Other committees

From: 23/03/2012
NHMRC
Postdoctoral Reference committee
committee member

Professional organisation memberships

From: 01/01/2000
Asia-Pacific Histocompatibility and Immunogenetics Association
member

From: 01/01/2001
Australasian Society for Immunology
member

From: 01/01/2010
The Transplantation Society of Australia and New Zealand
member

Languages

  • English

Citizenship

  • Australian citizen

Grants

Title:
Elucidating sub-clinical pathways to chronic rejection in lung transplantation and therapeutic implications.
Investigators:
Mifsud, N
Funding:
(2007 - 2011). National Health & Medical Research Council (NHMRC).
Title:
Cross-reactive T cells mediate allograft rejection in transplantation.
Investigators:
Kotsimbos, A, Mifsud, N, Tait, B
Funding:
(2009 - 2013). National Health & Medical Research Council (NHMRC).

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
CCSP as a biomarker post lung transplantation: genetic predisposition, abundance and function.
Supervisors:
Kotsimbos, T (Joint-co), Mifsud, N (Joint).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Investigating the function of natural killer cells during Immunological responses following human lung transplantation.
Supervisors:
Westall, G (Main), Kotsimbos, T (Associate), Mifsud, N (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
The combination of common viral hits and heterologous immunity strongly influences clinical outcomes in "at risk" lungs.
Supervisors:
Mifsud, N (Main), Kotsimbos, T (Associate), Nguyen, T (Associate).

Completed Supervision

Student:
Nguyen, T.
Program of Study:
Prevention of human cytomegalovirus disease after stem cell transplantation. (PHD) 2010.
Supervisors:
Schwarer, A (Main), Boyd, R (Associate), Mifsud, N (Associate).