Transcript It’s academic - University of Western Australia

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The School of Paediatrics and Child Health (SPACH) is based at Princess
Margaret Hospital
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75 staff members (clinical and postdoctoral academic staff, professional research
staff and administrative staff)
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50 PhD and Masters students
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7 Honours students
We collaborate closely with researchers at both PMH and the Telethon
Institute for Child Health Research (TICHR)
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Students conducting projects with supervisors at PMH
School
of Paediatrics and Child Health
and TICHR are often enrolled with SPACH
Princess Margaret
Hospital for Children
OVERVIEW OF SPECIFIC RESEARCH CONTRIBUTIONS TO THE
FIELD:
University of Western Australia
School of Paediatrics and Child
Health
W/Prof Susan
Prescott
The CAIR research programme focuses on the processes that influence the developing human immune system, particularly processes
which predispose to allergic diseases and asthma in early childhood. With strong clinical and laboratory activities the group has been
ideally placed to investigate to underlying immunological mechanisms, and to also examine clinically relevant applications and practical
solutions. This includes a number of clinical intervention studies for the prevention of allergic diseases. Key activities and discoveries
have been in the following areas:
1. Defining patterns of perinatal immunity that predispose to
immune dysfunction
Since the publication by Lancet of Prof Prescott’s (still highly cited) landmark studies on early immune development 1, 2 there has been
enormous ongoing interest in how early immune dysregulation leads to the development of disease, particularly allergic disease. These
publications made a major and significant contribution to the field and the current disease paradigm. More recently we have just
demonstrated novel difference in the innate immune development 3. There are a number of ongoing projects which are extending these
findings to investigate the underlying molecular mechanisms, and to this end we have recently defined novel differences in T cell
signalling (PKC zeta expression) in children that go on to develop allergic disease (below) 4. We have also initiated microarray studies
(not yet complete) to study the patterns of gene expression during the first 5 years of life in allergic and nonallergic chil dren. Primarily, this
is likely to lead to a better understanding of disease pathogenesis, and could ultimately provide novel molecular targets for future
prevention strategies.
2. Identifying better early markers of allergic disease.
This is becoming more critical as more effective allergy prevention strategies (such as primary allergen immunotherapy) are being
developed. For the first time, the team has recently discovered that the ‘fingerprint’ pattern of neonatal T cell PKC isozyme expression
significantly predicts subsequent allergic disease 4, and that the predictive effect was stronger than any other biological marker
(including Th1 IFNg responses). Moreover, we have demonstrated that an intervention designed to prevent allergic disease (maternal
dietary supplementation with fish oil) significantly modified the expression of the same neonatal PKC pathway4. With epidemic rates of
allergic disease this highly original finding addresses several key issues that are central to reducing the burden of disease through
prevention. Firstly, it provides a potential avenue for more accurate prediction of disease. Secondly, as our preliminary data suggests, this
could also be used to monitor the effect of interventions aimed at reducing allergic disease. Thirdly, exploring the role of this key
intracellular signalling molecule could lead to a better understanding of disease pathogenesis, and fourthly this could ultimately provide a
novel molecular target for future prevention strategies. Finally, understanding these aspects of early T cell development are also highly
relevant to other important issues in early life such as susceptibility to infection, vaccine responsiveness and autoimmune propensity. This
emphasizes the wide-ranging potential significance further studies planned in this area.
A/Prof Meri Tulic
3. Identifying early influences that may promote or protect from
allergic disease.
Another key area of CAIR research has been in defining early influences in that may predispose or help prevent the development of
asthma and allergic diseases. This includes a number of diverse projects including novel studies into the clinical immunologic effects of
supplementation with probiotic bacterial 5-8 and omega-3 polyunsaturated fatty acids 9, 10 in very early life. We are also currently
investigating the influence of antioxidant status on early immune development (in progress). The CAIR team have also investigated the
potential effects of environmental pollutants on immune development, including novel exploratory studies on persistent organic
pollutants (such as pesticides) 11, and novel studies on maternal smoking in pregnancy which have shown effects on key microbial
recognition receptors (toll like receptors) 12. We are now exploring the role of early allergen exposure 13 (early feeding to induce
tolerance) in a recently NHMRC funded ($2.2 million 2010-2013) DB-RCT in collaboration with Adelaide. Finally, we have provided
evidence that interactions at the maternofetal interactions during pregnancy also have the potential to influence early fetal immune
development 14. Our research in the area is ongoing with further important publications anticipated in the next 12 months.
New directions: exploring epigenetic mechanisms in the
Developmental Origins of Allergic Disease:
We have just received new NHMRC funding (2010-2013) to explore how epigenetic modifications15 influence patterns of early gene
expression and susceptibility to disease. This will help identify pathways through which environmental pressures are likely to be driving
the epidemic rise in allergic disease. This novel study will identify genes differentially expressed during early development in relation to
subsequent allergy (using whole genome microarray), and examine epigenetic regulation of these candidate pathways in relation to in
utero influences. This study is as the cutting edge of research into allergy pathogenesis and directly addresses the recent call for human
studies in this new field.
VACCINE IMMUNOLOGY
Assoc Prof Peter Richmond, Dr Andrew Currie,
Dr Lea-Ann Kirkham and Dr Selma Wiertsema
Immunological mechanisms involved in
childhood vaccination
Surveillance and
Epidemiology
Policy &
implementation
Licensure of
vaccine
Basic research:
immunology,
microbiology
Vaccine development
trials and Child Health
School ofClinical
Paediatrics
Princess Margaret
Hospital for Children
Paediatric Respiratory
Research
W/Prof Peter Le Souef
Ingrid Laing
Catherine Hayden
Brad Zhang
Immunogenetics of asthma,
infectious disease and evolution
of the immune system
School of Paediatrics and Child Health
Princess Margaret
Hospital for Children
Paediatric Respiratory
Research
W/Prof Peter Le Souef
Ingrid Laing
PAEDIATRIC
RESPIRATORY
Catherine Hayden
Brad Zhang
RESEARCH
Immunogenetics of asthma,
infectious disease and evolution
of the immune system
Clin Prof Stephen Stick, Assoc Prof
Graham Hall & Assoc Prof Peter Franklin
Asthma and Cystic Fibrosis research
Measurements of lung function and
disease progression
Environmental studies
Bronchial epithelial cell cultures
Therapeutic clinical trials
School of Paediatrics and Child Health
Princess Margaret
Hospital for Children
Paediatric Respiratory
Research
W/Prof Peter Le Souef
Ingrid Laing
PAEDIATRIC
RESPIRATORY
Catherine Hayden
Brad Zhang
RESEARCH
Immunogenetics of asthma,
infectious disease and evolution
of the immune system
Clin Prof Stephen Stick, Assoc Prof
Graham Hall & Assoc Prof Peter Franklin
Asthma and Cystic Fibrosis research
AEROSOL RESEARCH
GROUP
Measurements of lung function and
disease progression
Assoc Prof Sunalene
Environmental studies
Devadason
Bronchial epithelial cell cultures
Effectiveness of therapeutic inhalers
for children
Therapeutic clinical trials
Development of new paediatric inhaler
devices
School of Paediatrics and Child Health
Effects of inhaled pollutants
Princess Margaret
Hospital for Children
School of Paediatrics and Child Health
Princess Margaret
Hospital for Children
CHILDHOOD DIABETES AND OBESITY
Clin Prof Tim Jones & Dr Liz Davis
Epidemiology of Type 1 diabetes (T1DM) and
hypoglycaemia in T1DM
Studies into childhood obesity, insulin resistance and
progression to Type 2 diabetes
Research includes longitudinal observational studies,
clinical assessments such as exercise tests, hypoglycaemic
clamps and microvascular function, as well as cellular and
genetic studies
School of Paediatrics and Child Health
Princess Margaret
Hospital for Children
CHILDREN’S ONCOLOGY
GROUP W/Prof Cathy Cole
Phase II and II therapeutic clinical
trials
Lab-based mechanistic studies
DEVELOPMENTAL
NEUROSCIENCE GROUP
Assoc Prof Jonathan Foster
Profiling of hypothalamic-pituitary-adrenal (HPA) axis
function in adolescents
HPA axis function as a predictor of cognitive development
Teaching and Learning Research
Assoc Prof Pam Nicol
Investigating the effectiveness of different
teaching and learning techniques
Teaching of paediatric cardiac auscultation skills
School of Paediatrics and Child Health
Scenario based integrated resuscitation learning
Princess Margaret
Hospital for Children