La Gruta , Nicole - Monash University - Department of Biochemistry and Molecular Biology

研究领域

My research program is focused on understanding the key drivers of CTL response magnitude and immunodominance hierarchies following viral infection (Figure 1). My research utilizes a range of cutting edge approaches, including tetramer-based magnetic enrichment, retroviral transduction, and single cell multiplexed RT-PCR analysis of TCR usage (Figure 2), to enable an unprecedented dissection of the relative contributions of naïve CTL precursor frequency and quality, and antigen abundance in dictating these highly reproducible virus-specific CTL response hierarchies. This work provides novel insights into the critical determinants of antiviral CTL response hierarchies, which is relevant to the development of an improved understanding of optimal vaccine development/use, and potentially, for evolving strategies that minimize the emergence of untoward consequences, such as autoimmunity.

近期论文

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Quinn KM, Zaloumis SG, Cukalac T, Kan WT, Sng XY, Mirams M, Watson KA, McCaw JM, Doherty PC, Thomas PG, Handel A, La Gruta NL. Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8+ T cells in aged mice (2016) Proc Natl Acad Sci USA. 113(5):1333-8. Hardy MY, Girardin A, Pizzey C, Cameron DJ, Watson KA, Picascia S, Auricchio R, Greco L, Gianfrani C, La Gruta NL, Anderson RP, Tye-Din JA. Consistency in polyclonal T-cell responses to gluten between children and adults with celiac disease (2015) Gastroenterology. Jul 27. pii: S0016-5085(15)01007-0. Cukalac, T, Kan, W-T, Dash, P, Guan, J, Quinn, K.M., Gras, S., Thomas, P.G., La Gruta, N.L. Paired TCRαβ analysis of virus-specific CD8+ T cells exposes diversity in a previously defined ‘narrow' repertoire (2015) Immunol Cell Biol. 93(9):804-14. Clemens, EB., Doherty, PC., La Gruta, NL.*, Turner, SJ*. Fixed expression of single influenza virus-specific TCR chains demonstrates the capacity for TCRα- and β-chain diversity in the face of peptide-MHC class I specificity (2015) J Immunol. 194(3):898-910. Petersen, J., Montserrat, V., Mujico, J.R., Loh, K.L., Beringer, D.X., van Lummel, M., Thompson, A., Mearin, M.L., Schweizer, J., Kooy-Winkelaar, Y., van Bergen, J., Drijfhout, J.W., Kan, W.T., La Gruta, N.L., Anderson, R.P., Reid, H.H., Koning, F., Rossjohn, J. (2014) T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease. Nat Struct Mol Biol. 21(5);480-8. Cukalac, T*., Chadderton, J.*, Zeng, W., Cullen, J.G., Kan, W.T., Doherty, P.C., Jackson, D.C., Turner, S.J., La Gruta, N.L. (2014) The influenza virus-specific CTL immunodominance hierarchy in mice is determined by the relative frequency of high-avidity T cells. J Immunol. 192(9);4061-8. Cukalac, T., Chadderton, J., Handel, A., Doherty, P.C., Turner, S.J., Thomas, P.G., La Gruta, N.L. (2014) Reporducible selection of high avidity CD8+ T cell clones following secondary acute virus infection. Proc Natl Acad Sci USA. 111(4); 1485-90. Wiede F, La Gruta NL, Tiganis T. (2013) PTPN2 attenuates T cell lymphopenia-induced proliferation. Nat Commun. 5:3073. Scally SW, Petersen J, Law SC, Dudek NL, Nel HJ, Loh KL, Wijeyewickrema LC, Eckle SB, van Heemst J, Pike RN, McCluskey J, Toes RE, La Gruta NL, Purcell AW, Reid HH, Thomas R, Rossjohn J. (2013) A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. J Exp Med. 210(12): 2569-82. Thomas PG, Handel A, Doherty PC, La Gruta NL (2013) Ecological analysis of antigen-specific CTL repertoires defines the relationship between naive and immune T-cell populations. Proc Natl Acad Sci USA. Jan 29;110(5):1839-44.