Prince Henry's Institute 2008/09 Scientific Report

60 Pages·2010·1.21 MB·English

prince henry’s institute
2008/09 scientific report
phi scientific report 2008/09 | 1
CONTENTS
About Us 3
Research Overview 4
Research Highlights 2008/09 6
PHI in the Community 8
Monash Health Translation Precinct 9
Chairman’s Report 10
Director’s Report 11
Institute Governance 12
Research Report - Bone, Joint & Cancer 16
Research Report - Brain and Gender 17
Research Report - Cancer Drug Discovery 18
Research Report - Cardiovascular Endocrinology 19
Research Report - Clinical Andrology 20
Research Report - Embryo Implantation 21
Research Report - Endometrial Remodelling 22
Research Report - Growth Factor Signalling 23
Research Report - Implantation and Placental Development 24
Research Report - Male Fertility Regulation 25
Research Report - Metabolism and Cancer 26
Research Report - Ovarian Biology 27
Research Report - Ovarian Cancer Biomarkers 28
Research Report - Reproductive Development & Cancer 29
Research Report - Reproductive Hormones 30
Research Report - Sex Determination and Gonadal Development 31
Research Report - Steroid Receptor Biology 32
Commercialisation, Scientific Services and Clinical Facilities 33
Awards & Prizes, Service to the Scientific Community 35
Staff List 37
Students 39
Honorary Appointments 42
Committees 43
Publications 46
Invited Presentations 52
Visiting Speakers 54
Grant Funding 56
Community Support 57
Support Us 58
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ABOUT US
Prince Henry’s Institute is a not-for-profit medical research
institute located at Monash Medical Centre Clayton in
Victoria, Australia.

PHI has over 160 staff and students and our vision is to improve quality of life through the
investigation of hormones in the fields of reproductive health, cancer, obesity, bone health and
cardiovascular disease.

Since its inception in 1960 as the Medical Research Centre at the former Prince Henry’s
Hospital, we have made significant contributions to health and medicine. The past five decades
have seen major discoveries, impacting the lives of tens of millions of people across the globe.
Some highlights include:
• New technologies developed by PHI researchers to detect common hormone deficiencies.
• We were part of a team of researchers that, after several decades of intensive research,
discovered the reproductive hormone inhibin. This hormone was later used by PHI
researchers to produce the first blood test for ovarian cancer.
• PHI research played a key part in the development of a brand new class of drugs to treat
breast cancer - aromatase inhibitors.
• PHI studies have proven how the aromatase gene plays an essential role in breast cancer
development, sperm formation and the metabolism of body fat.
• PHI jointly developed and commercialised a biochemical test for the detection of endometrial
cancer.
• PHI studies have led to a new hormonal method of contraception for men which has
shown this can be an effective approach. We are now leading the Australian arm of a major
international late-stage clinical trial of male contraception.
Prince Henry’s Institute is:
- a partner of the Monash Health Translation Precinct (MHTP)
- an affiliated institute of Southern Health
- an affiliated institute of Monash University
- a member of the Cancer Council Victoria
- a member of the Victorian Breast Cancer Research Consortium Inc.
- an alliance partner with the Ovarian Cancer Research Foundation
- an accredited institute of the National Health and Medical Research Council
- supported by the Victorian Government’s Operational Infrastructure Support Program
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reseArcH overvIeW
PHI specialises in medical research that improves the detection, diagnosis
and treatment of serious health conditions that are controlled by hormones.
Hormones are made by almost If ovarian cancer is detected and critical need to increase contraceptive
every organ of the body and play a treated early survival rates increase options for women.
significant role in a person’s health and from less than 30% to 90%.
For many women, existing
wellbeing. Our primary research areas
We are committed to reducing the contraceptives are not acceptable or
are: Cancer, Cardiovascular disease,
number of women dying from ovarian not available. We are investigating new
Reproductive Health and Positive start
cancer by conducting research to find ways to prevent pregnancy as well as
to life and healthy ageing
an early detection test for the disease. block sexually transmitted diseases,
including HIV.
Endometrial cancer (cancer of the
Cancer uterus) We are also studying male hormone
contraception, how it affects sperm
Breast cancer Endometrial cancer is the most
production and action and whether
common gynaecological cancer. We
there are new opportunities to translate
Breast cancer is one of the leading
have identified factors that may affect
discoveries into effective contraception
causes of cancer related death in
the progression of this disease and are
methods.
Australian women, with one in 12
determining the success of blocking
women diagnosed with breast cancer
these factors as a form of treatment. Pre-eclampsia
before 75.
We are also working on an early
Pre-eclampsia is a life threatening
diagnostic test for those at high risk of
We have uncovered how certain
condition experienced during
developing endometrial cancer.
factors drive breast cancer growth,
pregnancy, which often causes
which is paving the way towards new
multi-organ failure in the mother and
targeted breast cancer treatments that
can result in death for both mother
block cancer growth with fewer side- Reproductive health
and baby. Onset of pre-eclampsia is
effects than current approaches.
sudden and as there is no cure the only
Fertility
treatment is pre-term delivery.
PHI researchers are also working to
Approximately 15% of Australian
identify why cancers such as breast
Pre-eclampsia is associated with
couples of reproductive age have
cancer spread to bone and determine
intrauterine growth retardation and
problems with fertility. PHI researchers
ways to limit this growth.
babies of low birth weight, which
are working to understand the role of
can increase the chance of long-
Ovarian cancer hormones in fertility and the changes
term health problems such as heart
with age.
While ovarian cancer isn’t the most disease, hypertension and diabetes in
common cancer, it is one of the most We are also working to understand adulthood.
frightening – because most women factors regulating sperm production
We are endeavouring to develop a
who are diagnosed with ovarian cancer and why this fails, causing infertility
test to predict high risk pregnancies
survive less than five years. and conversely how it can be used
for pre-eclampsia, allowing for better
for contraception when reversed and
Unlike cancers such as breast management of the condition and
suppressed.
cancer, there are no self-examination reducing life threatening risks to mother
techniques or discernible symptoms Contraception and baby.
of ovarian cancer and there is no
Between 1995 and 2000 more
conclusive way to make a diagnosis
than 700,000 women, most in
without surgery. Sadly the result is
the developing world, died due to
a very high proportion of late stage
causes associated with unintended
diagnoses, meaning the cancer is well
pregnancies. As a result the World
advanced and has often spread to
Health Organization has identified a
other parts of the body.
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Cardiovascular disease Our aim is to identify the genes that
cause disorders of sex development
Cardiovascular disease (heart, stroke
and the mechanisms underlying the
and blood vessel disease) is the
formation of testes and ovaries in an
leading cause of death in Australia,
embryo.
killing one Australian every ten minutes.
In 2006, 46,000 people died as a result Neurological Disorders
of cardiovascular disease, representing
Chromosomal differences between
a staggering 34% of all deaths.
men (XY) and women (XX), is a
Around 3.67 million Australians are key area of investigation for PHI
affected by cardiovascular diseases researchers who are especially
with 1.10 million Australians disabled interested in the SRY or ‘male only’
long-term as a result. Sadly, over the gene.
past decade, the prevalence of heart,
We are unravelling the genetic factors
stroke and vascular conditions in
that underlie gender differences
Australia has increased by 18.2%*.
in susceptibility to neurological
We are looking at the effects of disorders such as Parkinson’s disease,
hormones on the cardiovascular schizophrenia and drug addiction.
system in order to develop drugs that
Bone health
are better targeted to prevent cardiac
failure and treating cardiac problems
Osteoporosis and other conditions
such as hypertension.
that affect the skeleton, such as
orthopaedic implant failure and cancer-
* Statistics sourced from Heart Foundation
induced and inflammatory bone loss,
are an enormous health cost burden to
Australia.
Positive start to life and healthy
ageing Whilst there are several therapies
available to stop the breakdown of
Disorders of Sex Development
bone, the same is not true for therapies
that build new bone.
One percent of babies are born
with a disorder that affects their sex
We are working on new approaches
development, meaning their testes or
to treatments that build bone and
ovaries have not developed correctly,
investigating possible treatments for
their genitalia may not be distinctly
osteoporosis.
male or female, the development of
their sex anatomy may be incomplete
or they may have chromosome
abnormalities.
.
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RESEARCH HIGHLIGHTS 2008/09
2008 2009
Older men testosterone boost Breast cancer, hormones and Sticky proteins required for
A clinical study led by researchers at obesity link pregnancy
Prince Henry’s Institute provided strong A new molecular link was discovered Research, which may explain why
evidence that a testosterone boost that helps account for the increased some women have fertility problems,
could have the benefits for some older incidence of breast cancer in obese revealed how two proteins are needed
men. older women. for the embryo to successfully attach to

the inside of the uterus.
Allan CA, Strauss BJ, Burger HG, Forbes EA Brown KA, McInnes KJ, Hunger NI, Oakhill JS,
& McLachlan RI. (2008). Testosterone therapy Steinberg GR & Simpson ER. (2009). Subcellular Marwood M, Visser K, Salamonsen LA &
prevents gain in visceral adipose tissue and loss of localization of cyclic AMP-responsive element Dimitriadis E. (2009). Interleukin-11 and leukemia
skeletal muscle in nonobese aging men. Journal binding protein-regulated transcription coactivator inhibitory factor regulate the adhesion of
of Clinical and Endocrinology and Metabolism 93, 2 provides a link between obesity and breast endometrial epithelial cells: implications in fertility
139-146. cancer in postmenopausal women. Cancer regulation. Endocrinology 150, 2915-2923.
Research 69, 5392-5399.

3D view of sperm development
Sex reversal gene
Study links enzyme to family breast
pathway
A gene has been identified that is
cancer
PHI research has provided a 3D
important for male sex determination
A study showed that some women,
view of how genes and hormones
and the finding may help explain
known to be at high family risk of
interact in diverse ways during sperm
unexplained cases of Disorders of Sex
breast cancer, have higher levels
production. This understanding may
Development.
than other women of a key enzyme, also lead to novel approaches to male
Bagheri-Fam S, Sim H, Bernard P, Jayakody aromotase, in their breast tissues.
contraception.
I, Taketo MM, Scherer G & Harley VR. (2008).
Chand AL, Simpson ER & Clyne CD. (2009).
Loss of Fgfr2 leads to partial XY sex reversal. o’Donnell L, Pratis K, Wagenfeld A, Gottwald U,
Aromatase expression is increased in BRCA1
Developmental Biology 314, 71-83 Muller J, Leder G, McLachlan RI & Stanton PG.
mutation carriers. BMC Cancer 9, 148.
(2009). Transcriptional profiling of the hormone-

responsive stages of spermatogenesis reveals

Hormone changes in menopausal cell-, stage-, and hormone-specific events.
Gene link gender identity
transition Endocrinology 150, 5074-5084.
The largest ever genetic study of
A series of studies have shown how
male to female transsexuals found
hormones produced by the ovary are
a significant genetic link between
involved with the decline in eggs during Bone loss mechanisms
gender identity and a gene involved in
late reproductive life. A study found that an experimental
testosterone action.
drug with potential as a diabetes
Robertson DM, Hale GE, Fraser IS, Hughes CL
Hare L, Bernard P, Sanchez FJ, Baird PN, Vilain treatment causes rapid loss of bone.
& Burger HG. (2008). A proposed classification
E, Kennedy T & Harley VR. (2009). Androgen
system for menstrual cycles in the menopause Quinn JM, Tam S, Sims NA, Saleh H, McGregor
receptor repeat length polymorphism associated
transition based on changes in serum hormone NE, Poulton IJ, et al. Germline deletion of
with male-to-female transsexualism. Biological
profiles. Menopause 15, 1139-1144 AMP-activated protein kinase {beta} subunits
Psychiatry 65, 93-96.
reduces bone mass without altering osteoclast

differentiation or function. FASEB J. 2009 Sep 2.

Development of the ovary
Endometrial repair and activin
A study has shown that transforming
In a study that may lead to new
growth factor-beta inhibits follicle
treatments of abnormal uterine
development by increasing the rate of
bleeding problems it was shown that
follicle death.
endometrial repair is controlled by the
Rosairo D, Kuyznierewicz I, Findlay J & Drummond action of activin.

A. (2008). Transforming growth factor-beta: its role
in ovarian follicle development. Reproduction 136, Kaitu’u-Lino TJ, Phillips DJ, Morison NB &
Salamonsen LA. (2009). A new role for activin in
799-809.
endometrial repair after menses. Endocrinology

150, 1904-1911.

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Proteomics and establishing Immune cells and hypertension
pregnancy This research has demonstrated
Proteomics technology has been an important, unexpected role for
used to identify novel proteins key to the mineralocorticoid receptor in
establishing pregnancy. The study macrophage function and of the
showed how the enzyme PC6 is macrophage in determining the
regulated in the uterus. inflammation in cardiac fibrosis and

high blood pressure.
Kilpatrick LM, Stephens AN, Hardman BM,
Salamonsen LA, Li Y, Stanton PG, et al. rickard AJ, Morgan J, Tesch G, Funder JW,
Proteomic identification of caldesmon as a Fuller PJ & Young MJ. (2009). Deletion of
physiological substrate of proprotein convertase mineralocorticoid receptors from macrophages
6 in human uterine decidual cells essential for protects against deoxycorticosterone/salt-induced
pregnancy establishment. J Proteome Res. 2009 cardiac fibrosis and increased blood pressure.
Nov;8(11):4983-92. Hypertension 54, 537-543.

Identification of a protein which
inhibits the spread of cancer
A study showed how the molecule
betaglycan may affect cell behaviours
including the ability of ovarian cancer
cells to metastasise.

Bilandzic M, Chu S, Farnworth P, Harrison CA,
Nicholls P, Wang Y, escalona rM, Fuller PJ,
Findlay JK, Stenvers KL. 2009. Loss of betaglycan
contributes to the malignant properties of human
granulosa tumor cells. Mol Endocrinol. 23(4): 539-
548.

Ageing and female hormones
A detailed study has helped unpick the
complex relationships between several
female hormones involved in the
menstrual cycle and how these alter in
later life.

Robertson DM, Hale GE, Jolley D, Fraser IS,
Hughes CL & Burger HG. (2009). Interrelationships
between ovarian and pituitary hormones in
ovulatory menstrual cycles across reproductive
age. Journal of Clinical Endocrinology &
Metabolism 94, 138-144.

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PHI IN THE COMMUNITY
Medical research should never simply begin and end in the laboratory.
Central to research are the benefits it provides to the broader community.
PHI embraces the multiple opportunities to engage with the wider community,
to share how our discoveries are bringing science to life. The support and
generosity of the community also further enhances our capacity to undertake
research and for that we are very thankful.
Raising awareness and public PHI on the Internet through the CSIRO’s Scientists in
support for ovarian cancer Schools scheme. They have developed
In 2009 the Institute developed and
ongoing partnerships with teachers
In partnership with the Ovarian Cancer launched a brand new “community
and these special relationships
Research Foundation, our researchers friendly” web site. New social
broaden school students’ experiences
have provided scientific expertise at media initiatives such as Twitter and
in their science studies.
dozens of major community, education, Facebook also broadened the online
fundraising campaigns such as opportunities to promote the Institute’s Other researchers have gone on the
the NAB Silver Ribbon Appeal and latest discoveries. road with the Australian Society for
other social events such as L’Oréal Medical Research (ASMR) to visit

Melbourne International Fashion Week. schools through country Victoria. The
Community support of clinical
ASMR is the peak body for Australian
research
Media engagement medical researchers and in 2009 PHI
researcher Dr Sarah Meachem was
Hundreds of non-scientists play an
PHI research discoveries are promoted ASMR President. Sarah led dozens
essential role in the Institute’s research
through local, state, national and of further related events and activities
by supporting our research in a very
international media. which raised community awareness
special fashion. These are research
of Victorian medical research and
Major coverage in 2009 included our participants in clinical studies and trials
innovation.
research trial of male contraception, who are generous enough to give us
endometriosis research and the some of their time.
discovery of a molecular link between
Hundreds of Victorian women have
breast cancer and obesity, which was
actively supported our sample
featured nationally on ABC TV news.
collection for ovarian cancer research.
Also, during 2009, participant
Reliable health information for recruitment commenced for the
Victorians Melbourne arm of a major international
study of a new male contraceptive
Institute researchers provide scientific method. The male contraception study
expertise and editorial content for is supported by the World Health
multiple community health factsheets Organization.
which are available through the
Victorian Government’s website Better
Health Channel. Researchers in the community
Many PHI researchers are active in
school education initiatives which
promote careers in medical research
and innovation. Some researchers
have been matched with local schools
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MONASH HEALTH TRANSLATION
PRECINCT
The Institute is proud to be associated with Southern
Health, Monash University and Monash Institute of
Medical Research in the Monash Health Translation
Precinct (MHTP). The Precinct has been awarded
$71M by the Commonwealth Government towards the
development of a new translation research facility.
MHTP vision • To optimise productive interactions MHTP research themes are specifically
between MHTP partners and external aligned to national health priorities:
Monash Health Translation Precinct
stakeholders
(MHTP) will be a world leader in • cancer
delivering the best healthcare by • To increase efficiency in the utilisation
• cardiovascular
translating innovative scientific of shared resources and cutting edge
discoveries into best clinical practice platform technologies
• endocrinology and metabolism
in a dynamic and collaborative
environment. • Inflammatory and infectious diseases
MHTP key facts
• Men’s health
MHTP purpose
We are:
• Mental health and neurosciences
Monash Health Translation Precinct
• Prince Henry’s Institute – world
is dedicated to translating medical • Paediatrics
leaders in the field of endocrinology,
research to improve healthcare; uses
the study of hormones • Women’s health
clinical insights to focus the agenda
of basic research; is committed to • southern Health – victoria’s largest For further information about Monash
innovative research development and public health service providing uniquely Health Translation Precinct visit
enhances research collaboration. integrated care across the entire www.mhtp.org.au
lifespan

MHTP aims • Monash Institute of Medical
Research – leaders in stem cell,
• To develop the Precinct’s capacity for
infection, immunity and cancer
world-leading innovative translational
research
research
• Monash University – Australia’s
• To identify new opportunities for the
largest university with an international
translation of research into advances in
reputation for innovative health
healthcare
research
• To improve the health and wellbeing
The Precinct is located in Melbourne’s
of the population
South Eastern corridor within the
grounds of Southern Health’s 640 bed
• To encourage collaboration and
tertiary teaching and research hospital,
partnerships between clinicians and
Monash Medical Centre, and in close
researchers
proximity to some of Australia’s leading
research organisations and companies,
including the Australian Synchrotron,
Monash on-campus Centres, CSIRO
and emerging biotechnology entities.
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CHAIRMAN’S REPORT
The Institute’s report this year is the first under its
new structure. In 2009 PHI became a corporate
entity limited by guarantee, having previously
operated under the Prince Henry’s Institute of
Medical Research Act.
This change, recommended by the The coming year marks the 50th
Victorian Government and endorsed by anniversary of Prince Henry’s Institute
Parliament in 2008, allows the Institute and it is with great pride we look back
to operate under a structure that better over achievements of the past five
supports the Institute’s operations decades and see the contributions PHI
and governance as a modern medical has made to the world of medicine.
research institute.
Highlighted throughout this report
Changes to the Board have also are some recent scientific discoveries
occurred and I would like to made by our researchers such
acknowledge the contribution of former as discovering a molecular link
Board members Mr Richard Amos, Mrs that contributes to the increased
Margaret Lothian, Ms Carmel Mortell, incidence of breast cancer in obese
Mr Trevor Montgomery, Professor older women; demonstration of
Nicos Nicola, Mr John Robinson and the importance of immune cells in
Mr Bob Stensholt. hypertension; identifying a protein
which inhibits the spread of cancer
I would particularly like to thank
and finding that an experimental drug
Trevor Montgomery for his more than
with potential as a diabetes treatment
15 years of service during which he
results in rapid bone loss.
made significant and long lasting
contributions. Mr John Robinson, It is discoveries such as these and
should also be recognised for his their wide-reaching impact that are
leadership as the past Chairman of at the heart of PHI and why the work
the Board taking the Institute safely conducted here is so important. The
through its transition to a corporate new members of the Board are greatly
entity. impressed by the calibre of the PHI
research team and the importance of
The Institute has been fortunate to
the work conducted at the Institute.
secure new Board members - Ms
I hope readers of this report will gain
Jennifer Joiner, Professor Steve
insight into these discoveries as well
Wesselingh and Mr John Weste, who
the ones we are hoping to make in the
all bring with them a range of skills and
future.
expertise that will guide PHI through
the coming years.
The job of a Board is always easier Bob Edgar
when it has confidence in the Chairman
organisation’s operational leadership.
Institute Director Professor Matthew
Gillespie has now been with the
Institute for two years and on behalf of
the Board I would like to acknowledge
his leadership and direction.
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