Monash research contributing to personalised medicine for immune disease

Professor Richard Kitching

The development of individualised treatments for autoimmune diseases to improve the quality of life for patients is the aim of a new international research collaboration, including Monash University.

RElapse PrevENTion in autoimmune diseases, known as RELENT, is a multidisciplinary group of scientists, doctors and commercial partners from Europe. The consortium of nine scientific and four commercial partners has been funded by a 6.5 million Euro grant from the European Union’s Horizon 2020 research and innovation program and is coordinated by Professor Renate Kain, Medical University of Vienna. There is one investigator each from the US and Australia.

Professor Richard Kitching, Director of the Centre for Inflammatory Disease, School of Clinical Sciences at Monash Health, Monash University is a principal investigator and only Australian member of the RELENT program collaboration.

“More than 5% of the Australian population will develop an autoimmune disease in their lifetime, often associated with significant morbidity, mortality and economic cost,” said Professor Kitching.

“Autoimmune diseases can affect many parts of the body, including the small blood vessels in the kidneys critical to their function. In some people this results in both permanent kidney failure and damage to other organs.”

Severe autoimmune and inflammatory diseases currently need to be treated with long-term immunosuppressive drugs that have significant side effects.  Despite this, the outcome for individual patients varies considerably, with some people having difficult to treat disease with multiple relapses, whilst others have much less persistent disease.

“Currently, it is rarely possible to tailor immunosuppressive therapy to the individual needs of patients, as we can’t usually predict who will respond well and who will not in advance,” said Professor Kitching.

“While this can be frustrating for clinicians, it often has a huge impact on the lives of people with these diseases. We really need to understand these diseases better to be able to adapt treatments for each individual person.”

Professor Kitching said that by closing the knowledge gap in mechanisms of disease, the RELENT program will provide the scientific underpinning for more individualised, safer and more effective management for people with severe autoimmune and inflammatory disease.

"We currently have no means of distinguishing from the outset which patients will suffer from frequent relapses of their disease—and therefore need intensive early treatment—from those who will not,” said Professor Kain.  

“Personalising treatment according to the disease activity of individual patients is already a concept established in cancer treatment.”

“By combining clinical and serological data with genetic and transcriptomic signatures to unravel the molecular mechanisms that determine disease outcome, we will be able to develop customised health care for people suffering from autoimmune disorders," added Professor Kain.

The specific expertise of Professor Kitching’s research group is not available elsewhere in the world, and is the reason for Monash University’s inclusion in RELENT’s ambitious work program.

Monash University’s contribution is critical to the success of the RELENT program.

“The expertise of Monash’s team will help us know what actually happens in autoimmune disease, so that we can better customise treatments for each individual,” said Professor Kitching.

Monash research to improve outcomes for pancreatic cancer patients

Mr Dan Croagh

A collaborative research project including Monash Health pancreatic surgeon Mr Dan Croagh and Hudson Institute of Medical Research senior research fellow Professor Brendan Jenkins has been awarded a grant of $51,500 from the CASS Foundation to improve clinical treatment of pancreatic cancer.

Pancreatic cancer, an inflammation-associated cancer, is the fourth most common cause of cancer death worldwide, with an extremely low 5% five-year survival rate.

“Typically, studies look at gene expression patterns between normal pancreas and cancerous pancreas in order to identify unique signatures, which can be indicative of sensitivity or resistance to specific chemotherapeutic treatments,” said Professor Jenkins, Head, Cancer and Immune Signalling Laboratory, Centre for Innate Immunity and Infectious Diseases.

“To date, gene expression studies have largely focused on samples taken from open surgical biopsy; a procedure known to be very invasive and only possible in 20% of pancreatic cancers.”

Professor Jenkins’ research group at the Hudson Institute, in collaboration with Mr Daniel Croagh, Director of Research, Department of Upper Gastrointestinal and Hepatobiliary Surgery at Monash Medical Centre, recently trialled an alternative and less invasive process available to nearly all pancreatic cancer patients known as endoscopic ultrasound-guided fine-needle aspirate (EUS-FNA).

“EUS-FNA uses a thin, hollow needle to collect the samples of cells from which genetic material can be extracted and analysed,” said Mr Croagh, who is also a senior lecturer in the Department of Surgery, School of Clinical Sciences at Monash University.

“Our challenge is to ensure gene sequencing from EUS-FNA samples is comparable to open surgical biopsy such that established analysis and treatment can be used.”

Results from this study so far show that data from EUS-FNA-derived samples are of high quality and also allow the identification of gene expression signatures between normal and cancerous pancreas.

Professor Jenkins’ group is now confident that EUS-FNA-derived material not only has the potential to capture nearly all of pancreatic cancer patients (compared to ~20% by surgery), but to also improve patient management and their treatment in the clinic.

Professor Jenkins said that using next generation gene sequencing, involving big instruments, big data and big computing – allows near-term disruptive change in the clinical treatment of pancreatic cancer.

“Next generation sequencing at the Monash Health Translational Precinct (MHTP) Medical Genomics Facility will be performed to identify candidate known and hitherto unknown cancer driver genes via their altered gene expression (RNA) and/or mutational (DNA) status,” added Professor Jenkins.

The clinical study, once approved by ethics, will also be performed at Epworth under the leadership of Mr Daniel Croagh using the resources from Epworth’s Clinical Research Centre. 

“Upon the successful completion of our study, the primary outcome will be laying the foundation for the introduction into clinical practice of EUS-FNA as a standard method of screening pancreatic cancer patients for molecular "signatures" which can predict the responsiveness of individual tumours to current therapies.”

Importantly, such signatures could also provide novel molecular targets for future personalized therapeutics.

“Our study highlights the benefits provided by collaboration between clinician researchers and basic scientists,” said Mr Croagh. 

Ultimately, the research team aims to increase the number of pancreatic cancer patients that respond to personalized therapy, and therefore improve upon the overall poor 5-year survival rate which has remained stagnant at 5% over the last few decades.

Monash neonatologist awarded RACP fellowship for fetal treatment of congenital heart disease

Neonatologist Associate Professor Flora Wong has been awarded a competitive Royal Australasian College of Physicians (RACP) Fellows Research Establishment Fellowship for her project “Maternal hyperoxygeneration - a potential new fetal treatment for hypoplastic left heart syndrome”.

The multi-disciplinery project, in collaboration with the obstetricians at Monash University and Monash Health, and paediatric cardiologists from the Paediatric Heart Centre at Giessen, Germany aims to develop new fetal treatment for congenital heart disease.

“We are interested in the hypoplastic left heart syndrome,” said Associate Professor Wong.

“Babies with hypoplastic left heart syndrome require very complex cardiac surgery shortly after birth with high mortality and morbidities in survivors.”

Over the last few years Associate Professor Wong and her team have developed a novel percutaneous fetal cardiac catheterisation technique, published in the fetal lamb model.

“The technique involves accessing the fetal heart via the fetal liver, by needle puncture through the maternal abdomen, under ultrasound guidance,” added Associate Professor Wong.

“Utilising this state-of-the-art cardiac catheterisation technique, we have recently created a fetal lamb model of hypoplastic left heart by closing the fetal foramen ovale.”

With her RACP Fellowship, Associate Professor Wong plans to confirm the cardiac pathology in the fetal lamb model of hypoplastic left heart.

“We will utilise this fetal lamb model to test if giving the mother (the pregnant ewes) supplementary oxygen during pregnancy would mitigate the development of the hypoplastic left heart in the fetal lamb.”

“This treatment of maternal hyperoxygenation (mothers breathing in supplementary oxygen for >4 hours per day) may be a practical and easy-to–apply fetal therapy to arrest/reduce progression of hypoplastic left heart in-utero.”

Monash University and Monash Health collaborative study improves management of ear surgery

Research team photo with prize medal (L-R):
Mr Paul Paddle, Dr. Stacy Goergen,
Mr Guillermo Hurtado

A collaborative research study at Monash has received the prestigious Royal Australasian College of Surgeons RC Bennett Award for the best clinical research paper at the 2015 Victorian-Tasmanian Annual Surgical Meeting.

Led by Monash Health Ear Nose and Throat (ENT) surgeon Mr Paul Paddle, the study investigated the diagnostic accuracy of an imaging technique, Non Echo-planar diffusion weighted (non-EPI DWI) MRI in detecting recurrent cholesteatoma—an abnormal skin growth in the middle ear behind the eardrum.

With collaborators including Director of Research, Department of Imaging Professor Stacy Goergen, Monash Health ENT surgeon Mr Guillermo Hurtado and Alfred Health ENT surgeon Professor Vince Cousins, the blinded study also analysed the role of non-EPI DWI MRI in surgical decision-making in cholesteatoma.

Temporal Bones CT scan shows
 left middle ear
non-specific opacification

“In an Australian-first, this study validates the use of this specific MRI technique as an additional tool for the management of cholesteatoma,” said Mr Hurtado.

Cholesteatoma is a common, non-malignant but destructive lesion that can cause erosion of bones such as the ossicles, the mastoid process or the skull base. Management of cholesteatoma is challenging and requires complex middle ear surgery.

‘Cholesteatoma can develop in up to 10% of people with chronic suppurative otitis media (CSOM), a chronic inflammation of the middle ear and mastoid cavity,” said Mr Hurtado. 

“CSOM is a major public health issue, with the World Health Organization estimating between 65–330 million people worldwide being affected, mostly in the developing world.”

“Imaging techniques such as CT scan and MRI assist confirmation of clinical suspicion and postoperative evaluation, however, differentiation of cholesteatoma from other types of middle ear inflammation or postoperative changes is not yet available,” said Mr Hurtado.

Currently, revision surgery and histopathology analysis is the standard of care to exclude recurrence of cholesteatoma disease.

“Conclusions from our study will aid in the development of a formal cholesteatoma post-operative patient management protocol at Monash Health ENT Department,” added Mr Hurtado.

“Further research including additional cost-effectiveness analysis could potentially lead to reducing healthcare costs for the management of our large group of patients affected by cholesteatoma disease.” 

CDH Australia contributing to vital research

(L-R) CDH researchers Dr Kelly Crossley,
Dr Ryan Hodges, Dr Philip DeKoninck
and Ms Margaret Polacska

Until the birth of her first child, Margaret Polacska had never heard of CDH Australia.

Like all expectant mothers, Margaret was looking forward to a healthy baby and starting life as a family.  Tragically, her baby boy Noah died in December 2007 from a fatal form of congenital diaphragmatic hernia.

Babies born with congenital diaphragmatic hernia, or CDH have a hole in the diaphragm that allows the stomach, intestines and liver to move up into the chest, stopping normal lung growth. Unfortunately many babies with CDH die at birth.

Margaret joined volunteer-run charity CDH Australia soon after her loss, where she made friends and found support to help her through her heartbreaking grief.

Her gratitude for CDH Australia was such that she began volunteering for the charity, and Margaret now serves as their President.

Like Margaret, Head of Perinatal Services at Monash Health Dr Ryan Hodges had never heard of CDH Australia until a chance hallway conversation with one of his research staff whose son was born with CDH.

Senior lecturer and researcher Dr Hodges is leading a novel research project at The Ritchie Centre, Hudson Institute, Monash University into CDH.

“CDH occurs in approximately 1 in 2,500 births and remains lethal or associated with serious morbidity in a large number of cases—the devastating consequences of inadequate lung growth and development,” said Dr Hodges.

“Despite modern neonatal care, 30-50% of babies born with CDH die postnatally and long-term morbidity is common, with survivors at risk for thriving problems, neurological, neurodevelopmental and chronic lung disease.”

In Dr Hodges’ research project, babies in the womb undergo keyhole surgery, placing a balloon in their airways, trapping lung-liquid and helping lung growth. 

The aim of Dr Hodges’ research project is to establish whether human amnion epithelial cells

(hAECs), a type of placental stem cell, when administered antenatally to fetuses with CDH, can restore lung growth by promoting tissue regeneration and repair in utero.

CDH Australia has recently donated $30,000 towards Dr Hodges’ research project.

“Our contribution to Dr Hodges’ pilot study is indicative of our strong support for his work and it is the first time CDH Australia has been able to donate to research,” said Margaret.

“Our donation was made possible by parents of children with CDH, who generously donated in honour and in memory of their child.”

“CDH Australia receives no government funding and we support hundreds of CDH parents and their extended families each year, relying on donations and the passion, gratitude and commitment of our volunteers,” added Margaret.  

Margaret said that CDH Australia families are very excited about the potential advancements in survival rates due to Dr Hodges' pilot study.

“The longer-term vision for our research is to develop the next major advance in the management of the very preterm infant,” said Dr Hodges.

“Ultimately, we hope that our work will lead to the future healthy survival of babies

who may have otherwise died or survived with disability from prenatal lung disease.”

Donations to CDH Australia can be made online at http://cdh.org.au/donate.

Appointment of Director, Research and Graduate Research

Dr Svetozar (Steven) Kovacevic has been appointed Director, Research and Graduate Research in the Faculty of Medicine, Nursing and Health Sciences.  Steven completed his PhD in Microbiology at Monash University, and has worked as Principal Scientist at Pfizer Animal Health. 

More recently, Steven has worked as the UK Government’s Global Science and Innovation Network (SIN) representative in Australia, based at the British Consulate-General in Melbourne and reporting to the British High Commission in Canberra. We look to Steven commencing in the role on 18 January 2016.

Monash haematology research showcased at ASH Scientific Meeting in North America

Dr Sumita Ratnasingam with poster at
the ASH in Orlando, Florida.

An abstract presented by Monash Haematology Research Fellow Dr Sumita Ratnasingam at the American Society of Haematology (ASH) Scientific Meeting in Orlando, Florida last week has been selected for the "2016 Highlights of ASH in North America".

Published this month in Blood, the abstract Bortezomib Yields High Response Rates in Antibody-Mediated Autoimmune Hematological Diseases Refractory to Conventional Immunosuppression, is a collaborative research study led by Monash researchers including Dr Rathasingam, Associate Professor Stephen Opat and Associate Professor Jake Shortt.  Other contributors included collaborating clinicians from the Alfred, Monash and Peninsula Health.

“The authors describe the first case series of bortezomib use in autoimmune hematological disease,” said co-author Associate Professor Shortt.

“Building on an initial case from Monash Health that was reported in the New England Journal of Medicine (Shortt et al, NEJM, 2013; 368: 90-2), the anti-cancer drug bortezomib has now been successfully repurposed in a range of non-malignant immune-mediated diseases.”

Bortezomib was designed to kill myeloma cells—these arise from the part of the immune system that makes antibodies.

In autoimmune disease, antibodies from non-cancerous plasma cells are produced and these can attack normal tissues, including blood cells.

“On this basis, we have now used bortezomib ‘off-label’ to reduce antibody production in autoimmune disease, and it appears to be both effective and well tolerated,” added Associate Professor Shortt.

The novelty of this work merited selection showcasing in the ‘Highlights of ASH in North America, 2016’ program, which provides a re-cap of ‘stand out’ abstracts from the ASH meeting.

Investigators at Monash Haematology and the School of Clinical Sciences at Monash Health are currently developing a trial protocol in which to formally test this approach prospectively in patients.

Dr Jim Harris receives Abbvie grant to study mechanisms of rheumatoid arthritis

Dr Jim Harris

Congratulations Dr Jim Harris who has received a grant of $48,500 from pharmaceutical company Abbvie for his study “Autophagy in rheumatoid arthritis: effects of TNF blockade”.

Chief Investigator in the Lupus and Arthritis lab, Centre for Inflammatory Diseases, Dr Harris will study autophagy in cells from patients with rheumatoid arthritis.

“In this study we will look at the effect of TNF blockers, a common treatment for rheumatoid arthritis (RA) on autophagy, a cellular process involved in numerous immune cell functions,” said Dr Harris.

In addition, Dr Harris’ group will investigate autophagic responses in cells from patients with RA, to determine whether defects in this process might account for some of the inflammatory pathology in these patients.

“This is a chance for us to utilise our close connection to the rheumatology clinic and test important regulatory mechanisms in cells from patients with RA.”

BioMedVic ‘Researcher in Residence’ Scheme – closing date 5 February 2016

BioMedVic is excited to announce the launch of the 2016 round of its ‘Researcher in Residence’ Scheme – closing date 5 February 2016​.​

A short-term ‘Researcher in Residence’ opportunity will be provided for up to five (5) early career researchers from Biomedical Research Victoria Member organisations to be placed part-time in the Victorian office of one of a range of state and federal parliamentarians.

The Researcher in Residence will join the staff of the MP’s office on relevant work, most likely carrying out a short research project to provide evidence to support the development of science, innovation, health and/or biomedical research policy papers.  If applicable, the Researcher in Residence may also travel to Canberra with the MP on at least one occasion when parliament is sitting.

For more information and application criteria contact Dr Michelle Zajac​, ​

Strategic Initiatives Manager, BioMedVic (michelle.zajac@biomedvic.org.au).

Read more about this initiative here.

myResearch Project Team: Showcase (14 Jan) - Invitation and Call for Action

You are invited to attend the next myResearch project team ‘Showcase’ scheduled for 14 January 2016 (details attached here).

Overview

The primary goal of the myResearch project is to enhance support to researchers throughout the research lifecycle and enable high quality research services. Monash will implement IT systems that have been designed with researcher needs at the forefront, and that will enable all participants in managing and supporting research to perform their roles simply and easily.

The myResearch Project Team is hosting a series of walkthrough sessions (called 'Showcases') in 2016 to showcase features of the online solution and development of business processes to interested researchers and professional staff, throughout each phase of the myResearch project.

This is also another opportunity for the community to provide feedback to the Project Team throughout the project life-cycle.

Feedback from researchers and professional staff gained at these showcase sessions is important because it will assist the Project Team with the configuration of the online solution and business processes before final release.

Invitation to the Second Showcase

This showcase is open to researchers, academic management (e.g. Deans, Associate Deans, Heads of School) and professional staff.

The showcase will provide attendees with the following:

·           Demo of the online Pure system to:

·           facilitate expression of interest and peer review processes

·           ‘create and save’ an application (called ‘proposal’ in Pure)  

(Note: the online Pure proposal will replace the current paper-based coversheet)

·           Summary of the feedback received by a group of researchers, academic management and professional staff who have taken part in a guided exploration of Pure ‘create and save’ an application in Pure

·           First showing of Infonetica, the online system to be used by researchers to prepare and submit ethics applications

Date: Thursday, 14 January 2016

Time: 9:30 - 10:30 AM

Venue:  Clayton campus (for specific venue details please register your attendance below)

Can't attend in person?

Those that can't attend in person will be able to attend remotely via Zoom. Please register below and you will be sent a Google calendar invitation with the Zoom connection details.

Please register

If you would like to attend this Showcase, please register here:

https://my.monash.edu.au/news-and-events/bookings/provost/view/156011/

Once registered, the event will be entered into your Google calendar

If you would like to attend via Zoom, the relevant connection details will be added to the Google calendar invitation.

Unable to attend?

If you are unable to attend and would like to access the Powerpoint presentation slides and Zoom recording, you can do so from the myResearch google site.

If you have any questions about the details in this email, please don't hesitate to ask.

We look forward to seeing you soon.

myResearch (formerly IRAS) update

In 2016, Monash University will implement new systems and processes to support the research lifecycle through a project called myResearch. This project was formerly known as the Integrated Research Administration System (IRAS).

The new systems and processes will cover the following areas:

• Grant and contract applications
• Post-award management
• Research outputs
• Web profiles and CVs
• Ethics
• Reporting

Benefits
myResearch uses IT systems that have been designed with researcher needs at the forefront. Infonetica is the system that will support ethics management, and Pure is the system that will support all other areas.

Benefits include:

• The ability for researchers to create and submit applications for research funding online to enable internal review and approval, removing the need for paper forms and signatures
• Accessible information about grants and contracts at all stages, from application through to post-award, in an easy-to-navigate online environment, allowing visibility of the status of grant applications and awarded grants and research contracts
• Better overall management of research project milestones, making it easier to keep the information updated and current
• Improved recording of research publications data, including automatic harvesting of indexed research outputs, simplifying the process of manually adding research outputs to the system
• The ability for researchers to add and manage a broad range of activities to add to web profiles and CVs, providing a richer picture of academic achievements
• Submission of ethics applications online with clear visibility of the status of ethics approval and milestones throughout a project
• ​S​implified and common business processes across faculties and central divisions

​.​

Timing
There will be two Go Live dates in 2016:

·        Approx. March 2016 – Infonetica (ethics)

·        Mid-2016 – Pure (award management, research outputs, web profiles, CVs and reporting)

Once both systems and the new processes have been activated the current systems and processes (including Research Master and Ropes) will be decommissioned.
Opportunities for early viewing and feedback
We would like to encourage researchers and professional staff to provide feedback on the processes. We are running guided explorations on various topics, in which participants get to practise an activity utilising the new system and provide feedback to us. Business Change Managers within each Faculty or Division are able to arrange for staff to participate in these explorations.
We are also running workshops and showcases on advertised dates (see the Events section of the myResearch website). These are open to all researchers and professional staff. Staff will be able to view elements of the system, engage in discussion and provide feedback.
Researchers and professional staff are vital to the success of this implementation. We strongly encourage staff to participate, so that we can address issues and work towards better meeting user needs.

For more information, please see the myResearch website.

NHMRC ECF and CDF Incubator Programs

Please be aware that the Research Development team within MRO will again support NHMRC ​Early Career Fellowship (​ECF​)​ and ​Career Development Fellowship (​CDF​)​ applicants through dedicated research development support. This support is additional to the MRO compliance review and submission processes coordinated by our colleagues in the Medical and Health Sciences

​(MHS) ​team.

Support includes:

• ·        Strategic, in-depth draft review of full application content (in consultation with senior academics if required)
• ·        Access to past successful applications and exemplars
• ·        Recommendations for mentors or collaborators
• ·        Provision of guidance documents to support application development - including application templates with strategy tips informed by senior Monash researchers (available online)
• ·        Workshops (TBA early in the new year)

There may be some availability of peer review or mentorship by senior academics, but please note that this year MRO will not routinely coordinate peer review for ECF and CDF applicants.

​They​ will strongly encourage peer review through their networks.

Key dates for review are as follows:

	Research Development Priority Review Period*	MRO Compliance Close	NHMRC Close
ECF	25 Jan - 10 Feb 16	10 Feb 16	24 Feb 16
CDF	11 Feb - 25 Feb 16	25 Feb 16	9 March 16

*application drafts welcome anytime, with specific schemes receiving priority in the weeks immediately prior to the MRO compliance deadline

Please encourage applicants ​to notify the Faculty Research Office (medicine.research@monash.edu) of their intention to submit an ECF or CDF application, and ​to review the MRO Research Development intranet pages, which explains the process for requesting a review and includes useful guidance for applicants.  

NHMRC Health Tracker update at 18 December 2015

Headlines

View presentations from 2015 NHMRC Symposium on Research Translation Submit your feedback: public consultation on Australian Drinking Water Guidelines Release of a costed list of standard items for clinical trials Development of a new Human Research Ethics Application (HREA) Update on Health Translation Advisory Committee (HTAC) activities Read all updates here.

Congratulations Dr Andrew Edwards on the award of his Doctor of Medicine

Dr Andrew Edwards

The Monash Institute of Graduate Research is pleased to report that Dr Andrew Edwards has been awarded the degree of Doctor of Medicine.

Dr Edwards' thesis titled: "Fetal therapy” was ratified by the Graduate Research Steering Committee on  Tuesday 8th December 2015 and will be conferred upon graduation.

Dr Edwards  presented a series of publications that address three broad aspects of fetal therapy: the impact of a common therapeutic intervention (corticosteroids) given to fetuses at risk of preterm delivery, the management of twin twin transfusion syndrome, and the development of an animal model / novel catheterisation process that has the potential to revolutionise management of structural cardiac malformations. 

Dr Edwards' papers represent a substantive and original contribution to our knowledge and understanding of various aspects of fetal therapy.

Sincere thanks to all the academic and professional staff involved in assisting Dr Edwards achieve this wonderful result.

Congratulations Jane Hayman on the award of her PhD

The Monash Institute of Graduate Research is pleased to report that Ms Jane Hayman has been awarded the degree of Doctor of Philosophy.

Jane's thesis titled: "Raising awareness of bowel cancer through workplace screening programs"  was ratified by the Graduate Research Steering Committee on  Tuesday 8th December 2015 and will be conferred upon graduation.

Sincere thanks to all the academic and professional staff involved in assisting Jane achieve this wonderful result.

Associations of calf inter- and intra-muscular adipose tissue with cardiometabolic health and physical function in community-dwelling older adults.

David Scott et al. published in the Journal of Musculoskeletal and Neuronal Interactions.

Read article here.

Methods in renal research: Kidney transplantation in the rat

David Nikolic-Paterson et al. published in Nephrology.

Read article here.