The Centre for Personalised Immunology

Enquiries

Centre Administrator

cpi.admin@anu.edu.au

Executive Officer

Edward Bertram

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Patient enquiries

cpi.info@anu.edu.au

Doctors enquiries

Matthew Cook

The Centre for Personalised Immunology (CPI) was established in April 2014 to help people with immune diseases by discovering causative genetic variation with the goal of delivering treatment strategies targeted to the individual. The principal objective of the Centre for Personalised Immunology is to understand pathophysiological pathways in patients presenting with immunological disease, in order to make diagnoses more accurate, and treatment more effective.

The Centre for Personalised Immunology provides an energetic, collaborative inter-disciplinary academic structure for research students with access to state of the art technologies and equipment. The centre provides the opportunity for students to be uniquely multi-skilled by working on projects across diverse areas. There are a variety of opportunities for science or medical graduates to undertake Honours, MSc or PhD degrees with the Centre.

Partners

Research projects

The CPI will consolidate the efforts of many research groups who have established and are investigating different patient cohorts. The expected collective benefit from a combined effort is to enhance the pace of translation by implementing an efficient platform for discovery and translation that all groups can access. Technical developments be accelerated by the assembled expertise and progress will be synergistic. We expect complementary information about disease pathways to arise from concurrent analysis of autoimmune, autoinflammatory and immune deficiency diseases. Our assembled significant and diverse patient cohorts will ensure access to both monogenic and more genetically complex cases in each of the disease categories under investigation in the centre. By including many different research groups and patient cohorts in the CPI, where all groups will be able to access streamlined sequencing and technology for proof of causation, the CPI will alleviate bottlenecks to translation and ensure maximum clinical benefit to a diverse group of patients at the earliest opportunity. In the past decade, analysis of patients from within our established cohorts has provided the basis for discovery projects that have yielded proof-of-principle for components of the CPI.

We are still recruiting to these cohorts. Additional patient cohorts will be analysed in the centre. For rare diseases, access to international cohorts of similar patients increases our chances of identifying and confirming causal alleles, and allelic series, which are important for understanding gene mechanism.

CPI patient cohorts: established and recruiting

Immune deficiency

  • Primary antibody deficiency (PAD)

    • ​​The ANZADA (Australia and New Zealand Antibody Deficiency Allele) cohort led by Professor Cook and Associate Professor Fulcher.
  • Primary immune deficiency (PID)
    • ​​Ulm cohort: severe combined immunodeficiency cohorts led by Professor Schwarz.
    • Freiburg Cohort: (S)CID cohort led by Professor Ehl and Professor Schwarz.

Autoinflammatory diseases

  • Vasculitis

    • ​​Monash and Canberra cohorts with ANCA-positive focal necrotising glomerulonephritis and/or systemic vasculitis. The Monash cohort is led by Professor Kitching and the Canberra cohort is led by The Canberra Hospital's nephrologist, Dr Giles Walters, and immunologist, Professor Cook.
    • Children’s Hospital at Westmead (CHW) Kidney Gene Bank. Associate Professor Alexander and colleagues have identified families with vasculitis and autoimmune and vascular diseases.
  • Systemic Juvenile Idiopathic Arthritis; Non bacterial osteitis
    • ​​​Recruited by Dr Grewal-Singh.
  • Haemophagocytic lymphohistiocytosis (HLH)
    • ​Australian cohort from Sydney, Canberra, Melbourne and Brisbane unexplained by known genetic causes will be analysed in collaboration with Dr Ehl.
  • Sarcoidosis
    • Cohort recruited by Professor Cook.

Current Research Projects

  1. Novel assays to rapidly and efficiently determine the effects of point mutations on immune system function
  2. Developing a CRISPR/Cas9 system to rapidly replicate and examine patient cellular phenotype
  3. Novel geno-phenotype biomarkers: improving diagnosis and determination of outcomes in SLE
  4. Utilising the CRSPR/Cas9 system to evaluate novel variants in aHUS
  5. Using genome-editing tools to generate mouse models based on genome-based mutation discovery
  6. Targeting SLE treatment based on geno-phenotype: pre-clinical trials in novel mouse models
  7. Prediction of patient outcomes and response to treatment based on geno-phenotype
  8. Using peripheral blood phenotype to improve identification of pathogenic mutations
  9. Screening for novel molecular pathways in PID
  10. Understanding the contribution of copy number variation in autoimmune disease
  11. Identification of pathogenic variants in uncharacterised disease genes through mining with gene network information
  12. An autoimmune disease gene and pathway ontology for mining human genetic variation data
  13. Novel inflammatory pathways influencing the initiation and outcome of vasculitis
  14. Treating inflammatory kidney injury by targeting pathway-specific humoral and cellular mediators

Diseases

The CPI works on a range of Immune Deficiency, Autoimmune and Autoinflammatory diseases. Some key examples of these include:

Systemic lupus erythematosus

A chronic autoimmune disease which has many different clinical manifestations including arthritis, pleurisy, mouth ulcers, rashes, blood clots, and nephritis. Laboratory abnormalities include autoantibodies (eg anti-double-stranded DNA antibodies), and evidence of antibody-mediated inflammation (low complement). The variation in clinical presentation from one SLE patient to another is substantial, raising the possibility that many different mechanisms might explain the disease.

Common variable immune deficiency

A cluster of diseases unified by the presence of antibody deficiency, which results in increased susceptibility to infections, especially pneumonia. Curiously, CVID is sometimes also complicated by autoimmunity, particularly affecting the blood cells. CVID can also be complicated by inflammatory lesions identical to those observed in sarcoidosis. Management of CVID requires lifelong antibody replacement with plasma products derived from healthy donors.

Systemic vasculitis

A group of rare and inflammatory diseases of the blood vessels. Although almost any organ can be affected, there is a predilection for kidney, lung and skin involvement. In some cases, vasculitis is associated with production of autoantibodies (eg anti-neutrophil cytoplasmic antibodies, or ANCA), but in others there is no conclusive evidence of autoimmunity. All forms of vasculitis are associated with profound and severe inflammation that requires treatment often with corticosteroids and cytotoxic agents.

Sarcoidosis

A disorder characterised by formation of granulomatous inflammation in the lymph nodes of the chest, salivary glands, skin, and sometimes other organs. In addition to inflammation, sarcoidosis is often associated with mild immune deficiency. In some cases, sarcoidosis is self-limited, but in others, long-term immunosuppression is required to prevent organ damage.

Technology platform

Scope of the Centre for Personalised Immunology

The CPI will operate simultaneously at the cutting-edge of biomedical research while implementing genomics into medical practice. We will tackle autoimmune, immune deficiency, and autoinflammatory diseases, with the aim of discovering the molecular and cellular mechanisms of disease in both rare cases of Mendelian disease and common immune diseases. Whole genome sequencing will be central to discovery; the centre has developed the necessary expertise in this domain (see below). The principal aim, however, is to discover disease pathways. This task is most achievable in Mendelian disease, but the greatest potential for clinical progress is to understand pathways to complex disease.

CPI diagram

The CPI platform comprises six modules 

  1. encompassing detailed laboratory-based phenotyping 
  2. comprehensive identification and verification of rare and potentially causal variants
  3. analysis of the biochemical and cellular consequences of the mutation
  4. proof of causation by complementation of human cell lines, or by engineering the precise point mutation in mice using DNA editing techniques (CRISPR/Cas9)
  5. identification of pathway biomarkers that can be applied to the disease cohort to identify subgroups affected by the same pathogenic route to disease
  6. and testing of pathway-specific therapy in the newly-generated mouse models

Facilities

The Centre for Personalised Medicine uses state-of-the-art infrastructure located on ANU campus including:

People

Chief Investigators

Professor Carola Vinuesa

The John Curtin School of Medical Research 

Professor Matthew Cook

The John Curtin School of Medical Research 

Professor David Fulcher

The John Curtin School of Medical Research 

Professor Stephen Alexander

Westmead Hospital | The University of Sydney

Professor Richard Kitching

Monash University

Dr Anselm Enders

The John Curtin School of Medical Research

Dr Rafael Casellas

NIH/NIAIDS | United States of America

Dr Klaus Schwarz

University of Ulm | Germany

Professor Mauricio Arcos-Burgos

The John Curtin School of Medical Research

Mr Matthew Field

The John Curtin School of Medical Research

Dr Dan Andrews

The John Curtin School of Medical Research

Advisory Board

Mr Peter Yates AM (Chairman)

Deputy Chairman of The Myer Family Investments Ltd and a Director of AIA Australia Limited.

Ms Nicole Feely

Director-General, ACT Health Directorate.

Professor Simon Foote FFSc (RCPA), FAHMS, FTSE

Director of The John Curtin School of Medical Research, The Australian National University.

Professor Oliver Mayo FAA FTSE

Honorary Research Fellow, CSIRO Animal, Food and Nutrition. Adjunct Professor, Faculty of the Sciences, University of Adelaide.

Dr Sue Meek AO FTSE

Chief Executive, Australian Academy of Science.

Dr Keats Nelms

Director, Business Development, The Australian National University.

Professor Virginia Pascual MD PhD

Director, Center for Inflammation and Autoimmune Diseases Director, Center for Personalized Medicine (Baylor Research Institute).

Associate Investigators

Professor Rajiv Khana

Leads the Tumour Immunology Laboratory at QIMR and is the director of the QIMR Berghofer Centre for Immunotherapy and Vaccine Development. 

Professor Chris Goodnow

Pioneer of large-scale mouse immunogenomics projects.

Professor Ian Alexander

Heads the gene therapy group at the CMRI in the Westmead Hub.

Associate Professor Russell Dale

NHMRC fellow and paediatric neurologist.

Dr Davinder Singh Grewal

Paediatrician and Paediatric Rheumatologist.

Professor Stephan Ehl

Head of the Centre for Chronic immunodeficiency at the University of Freiburg.

Professor Robert Brink

Head of the Immunology Research Division at the Garvan Institute.

Dr Jalila Alshekaili

Immunopathologist in Oman.

Dr Keats Nelms

Director of Business Development at The Australian National University.

Professor Nicholas Glasgow 

Dean Medicine & Health Sciences and Dean Medical School College of Medicine Biology & Environment, The Australian National University.

Project Leaders

Dr Vicki Athanasopoulos

(Postdoctoral Fellow, ANU) CRISPR/Cas9 editing.

Dr Fabienne Brilot-Turville

(Postdoctoral Scientist, CHW) Autoimmune brain disease.

Dr Julia Ellyard

(Postdoctoral Fellow, ANU) Genetic basis of organ-specific autoimmunity.

Dr Jeff Fletcher

(Paediatric Nephrologist, The Canberra Hospital) National registry of renal genetic disease.

Dr Poh Gan

(Postdoctoral Fellow, Monash University) Effector pathways in renal vasculitis.

Dr Simon Jiang

(Nephrologist and PhD student ANU) Genetics of systemic autoimmunity.

Dr Hugh McCarthy

(Nephrologist, CHW, completing PhD) Genetics of Nephrotic Sd.

Dr Andrew Mallett

(Nephrologist completing PhD at UQ SIA) Renal genetic testing.

Dr Joshua Ooi

(Postdoctoral Fellow, Monash University) Effector pathways in renal vasculitis.

Dr Katrina Randall 

(Senior Lecturer, ANU) Primary immune deficiency.

Dr Rebecca Sweet 

(Postdoctoral Fellow, ANU) Pathogenesis of SLE.

Dr Giles Walters

(Nephrologist at The Canberra Hospital) Pathogenesis of vasculitis.

Dr Yuan Min Wang 

(Post Doctoral Fellow in SIA lab CHW) Autoimmune renal disease.

Dr Zuopeng Wu

(Postdoctoral Fellow, ANU) Pathogenesis of HLH and sarcoidosis.

Support Staff

Dr Ed Bertram

Executive Officer, Centre for Personalised Immunology, The John Curtin School of Medical Research, The Australian National University

Mrs Doris Morales

Administrator, The John Curtin School of Medical Research

Dr Madeleine Nicol

Outreach and Communications, Centre for Personalised Immunology, The John Curtin School of Medical Research

Ms Anastasia Wilson

Nurse/Patient Enrolments, Centre for Personalised Immunology, The John Curtin School of Medical Research

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Updated:  29 April 2017/Responsible Officer:  Director, JCSMR/Page Contact:  Web Manager