Understanding the mechanisms of immune diseases.
At the Centre for Personalised Immunology, we study novel genes using cutting edge technology. We believe the greatest potential for translating genomic research into clinical care is through studying complex disease pathways.
Research GenomicsComprehensive identification and verification of rare and potentially causal variants.
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Models of DiseaseProof of causation by complementation of human cell lines, or by engineering the precise point mutation in mice using DNA editing techniques.
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Informing TreatmentTesting of pathway-specific therapy in the newly-generated mouse models.
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Our Approach.
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CPI has a new approach that uses genomic technologies that have only become available in the last few years. This approach enables CPI to identify genes and genetic mutations involved in immune disease development. Biological pathways affected in immune diseases can be identified resulting in new drug targets and diagnostics. The net effect is improved treatment of immune disease by removing the potentially severe side effects of current treatments.
The critical first step in the CPI approach is determining each patient’s genetic code (genome) through genome sequencing. Using advanced bioinformatics the CPI clinical researcher can identify from thousands of genetic variations in the genome those that could contribute to causing the disease. Sometimes the gene identified will be well described, or in a pathway that is known, but the impact from the particular variant may not be well understood. Often the gene that causes the disease is not obvious. Further research work is required to identify and understand how it works so that treatments can be developed. CPI also has the unique capability to transfer specific genetic mutations from patients into cells and models in order to confirm the function of the mutated genes. CRISPR/Cas9 genome editing enables CPI to create human cell lines and models carrying the specific human disease variant in isolation for validation of causality. The key difference between the CPI and other research is that whilst other research identifies associations with diseases pathologies, the CPI approach identifies cause and effect. The causal genetic variants enable CPI to better classify people into specific groups based on pathways to help refine diagnosis and provide more effective “personalised” treatment. |
Recent Publications.
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P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance.
He Y, Gallman AE, Xie C, Shen Q, Ma J, Wolfreys FD, Sandy M, Arsov T, Wu X, Qin Y, Zhang P, Jiang S, Stanley M, Wu P, Tan J, Ding H, Xue H, Chen W, Xu J, Criswell LA, Nititham J, Adamski M, Kitching AR, Cook MC, Cao L, Shen N, Cyster JG, Vinuesa CG. J Exp Med. 2022 Jan 3;219(1):e20211004. doi: 10.1084/jem.20211004. Epub 2021 Dec 10. PMID: 34889940; PMCID: PMC8669517. Inborn Errors of Immunity and Their Phenocopies: CTLA4 and PD-1. Hao Y, Cook MC. Front Immunol. 2022 Jan 28;12:806043. doi: 10.3389/fimmu.2021.806043. PMID: 35154081; PMCID: PMC8832511. Subcutaneous Gammanorm® by pump or rapid push infusion: Impact of the device on quality of life in adult patients with primary immunodeficiencies. Warnatz K, Jolles S, Agostini C, Vianello F, Borte M, Bethune C, Grigoriadou S, Richter A, Jain R, Lowe DM, Katelaris C, Milito C, Cook MC. Clin Immunol. 2022 Feb 1;236:108938. doi: 10.1016/j.clim.2022.108938. Epub ahead of print. PMID: 35121105. Neutrophil extracellular traps and their histones promote Th17 cell differentiation directly via TLR2. Wilson AS, Randall KL, Pettitt JA, Ellyard JI, Blumenthal A, Enders A, Quah BJ, Bopp T, Parish CR, Brüstle A. Nat Commun. 2022 Jan 26;13(1):528. doi: 10.1038/s41467-022-28172-4. PMID: 35082281; PMCID: PMC8792063. Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease. Jiang SH, Mercan S, Papa I, Moldovan M, Walters GD, Koina M, Fadia M, Stanley M, Lea-Henry T, Cook A, Ellyard J, McMorran B, Sundaram M, Thomson R, Canete PF, Hoy W, Hutton H, Srivastava M, McKeon K, de la Rúa Figueroa I, Cervera R, Faria R, D'Alfonso S, Gatto M, Athanasopoulos V, Field M, Mathews J, Cho E, Andrews TD, Kitching AR, Cook MC, Riquelme MA, Bahlo M, Vinuesa CG. Cell Rep Med. 2021 Dec 21;2(12):100475. doi: 10.1016/j.xcrm.2021.100475. PMID: 35028616; PMCID: PMC8714939. CD4+ T cells that help B cells - a proposal for uniform nomenclature. Eisenbarth SC, Baumjohann D, Craft J, Fazilleau N, Ma CS, Tangye SG, Vinuesa CG, Linterman MA. Trends Immunol. 2021 Aug;42(8):658-669. doi: 10.1016/j.it.2021.06.003. Epub 2021 Jul 6. PMID: 34244056; PMCID: PMC8324560. Personalizing medicine and technologies to address the experiences and needs of people with multiple sclerosis Henschke A, Desborough J, Parkinson A, Brunoro C, Fanning V, Lueck C, Brew-Sam N, Bruestle A, Drew J, Chisholm K, Elisha M, Suominen H, Tricoli A, Phillips C, Cook M. J Pers Med. 2021 Aug 12;11(8):791. doi: 10.3390/jpm11080791. Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus. Lea-Henry TN, Chuah A, Stanley M, Athanasopoulos V, Starkey MR, Christiadi D, Kitching AR, Cook MC, Andrews TD, Vinuesa CG, Walters GD, Jiang SH. Lupus. 2021 Oct;30(11):1756-1763. doi: 10.1177/09612033211033979. Epub 2021 Jul 16. PMID: 34266320. Structural and functional analysis of target recognition by the lymphocyte adaptor protein LNK Morris R, Zang Y, Ellyard JI, Vinuesa CG, Murphy JM, Laktyushin A, Kershaw NJ, Babon JJ. Nat Commun. 2021 Oct 20;12(1):6110. doi: 10.1038/s41467-021-26394-6. PMID: 34671038; PMCID: PMC8528861. Expanding the clinical spectrum of pathogenic variation in NR2F2: Asplenia Arsov T, Kelecic J, Frkovic SH, Sestan M, Kifer N, Andrews D, Adamski M, Jelusic M, Cook MC. European Journal of Medical Genetics. 2021 October, 64(4):104347. doi:10.1016/j.ejmg.2021.104347. Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus. Jiang, S.H., Athanasopoulos, V., Ellyard, J.I., Chuah, A., Cappello, J., Cook, A., Prabhu, S.B., Cardenas, J., Gu, J., Stanley, M. and Roco, J.A., 2019. Nature communications. 10(1), p.2201. Gain-of-function IKBKB mutation causes human combined immune deficiency. Cardinez C, Miraghazadeh B, Tanita K, Chand R, da Silva E, Hoshino A, Okada S, Chand R, Asano T, Tsumura M, Yoshida M, Ohnishi H, Kato Z, Yamazaki M, Okuno Y, Miyano S, Kojima S, Ogawa S, Andrews TD, Field M, BurgioG, Vinuesa CG, and Cook MC. J Exp Med. DOI: 10.1084/jem.20180639 |
More Publications
Robson KJ, Ooi JD, Holdsworth SR, Rossjohn J, Kitching AR. HLA and kidney disease: from associations to mechanisms. Nature Reviews Nephrology 2018 October Issue, https://doi.org/10.1038/s41581-018-0057-8
Dorjbal B, et al Hypomorphic CARD11 mutations associated with diverse immunologic phenotypes with or without atopic disease. J Allergy Clin Immunol. 2018 Aug 28. pii: S0091-6749(18)31201-6. doi: 10.1016/j.jaci.2018.08.013. [Epub ahead of print]
Hosking L, Bannister E, Cook MC, Choo SC, Kumble S, Cole T. Trichohepatoenteric syndrome presenting with immunodeficiency and later onset diarrhoea. J Clin Immunol. 2018 Jan;38(1):1-3. doi: 10.1007/s10875-017-0460-0.
Arsov, T., Sestan, M., Cekada N., Frkovic, N., Andrews, TD., He, Y., Shen, N., Vinuesa CG.,* and Jelusic, M*. Systemic Lupus Erythematosus: A New Autoimmune Disorder in Kabuki Syndrome. Eur J Med Gen. 2018. doi: 10.1016/j.ejmg.2018.09.005. [Epub ahead of print]
Pucar PA, Hawkins CA, Randall KL, Li C, McNaughton E, Cook MC. Comparison of enzyme-linked immunosorbent assay and rapid chemiluminescent analyser in the detection of myeloperoxidase and proteinase 3 autoantibodies. Pathology. 2017 Jun;49(4):413-418. doi: 10.1016/j.pathol.2017.02.006
Walters G and Vinuesa CG 2015. T Follicular Helper cells in Transplantation. Transplantation. 2015. Transplantation. 2016 Aug; 100(8):1650-5.
Jiang SH, Shen N, Vinuesa CG, 2015. Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity. Curr Opin Immunol., 37, 21-7.
Lee, C. E., Fulcher, D. A., Whittle, B., Chand, R., Fewings, N., Field, M., Andrews, D., Goodnow, C. C. & Cook, M. C. 2014. Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood, 124, 2964-72
Dorjbal B, et al Hypomorphic CARD11 mutations associated with diverse immunologic phenotypes with or without atopic disease. J Allergy Clin Immunol. 2018 Aug 28. pii: S0091-6749(18)31201-6. doi: 10.1016/j.jaci.2018.08.013. [Epub ahead of print]
Hosking L, Bannister E, Cook MC, Choo SC, Kumble S, Cole T. Trichohepatoenteric syndrome presenting with immunodeficiency and later onset diarrhoea. J Clin Immunol. 2018 Jan;38(1):1-3. doi: 10.1007/s10875-017-0460-0.
Arsov, T., Sestan, M., Cekada N., Frkovic, N., Andrews, TD., He, Y., Shen, N., Vinuesa CG.,* and Jelusic, M*. Systemic Lupus Erythematosus: A New Autoimmune Disorder in Kabuki Syndrome. Eur J Med Gen. 2018. doi: 10.1016/j.ejmg.2018.09.005. [Epub ahead of print]
Pucar PA, Hawkins CA, Randall KL, Li C, McNaughton E, Cook MC. Comparison of enzyme-linked immunosorbent assay and rapid chemiluminescent analyser in the detection of myeloperoxidase and proteinase 3 autoantibodies. Pathology. 2017 Jun;49(4):413-418. doi: 10.1016/j.pathol.2017.02.006
Walters G and Vinuesa CG 2015. T Follicular Helper cells in Transplantation. Transplantation. 2015. Transplantation. 2016 Aug; 100(8):1650-5.
Jiang SH, Shen N, Vinuesa CG, 2015. Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity. Curr Opin Immunol., 37, 21-7.
Lee, C. E., Fulcher, D. A., Whittle, B., Chand, R., Fewings, N., Field, M., Andrews, D., Goodnow, C. C. & Cook, M. C. 2014. Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood, 124, 2964-72
Infrastructure.
ACRF Biomolecular FacilityCore lab with experience in molecular genetics, protein technologies and bioinformatics.
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NCIAustralia's national research computing service, providing access to advanced computational infrastructure.
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Australian Phenomics FacilitySpecialised facility for developing, characterising, and archiving mouse models of human disease.
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Funding Institutions.
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You can learn more about research at the centre through our youtube channel, facebook page and twitter account.
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