Monash has new Sub-Faculty of Translational Medicine and Public Health

Professor Stephen Jane, newly

appointed Foundation Dean

Professor Margaret Gardner, Monash University Vice-Chancellor announced yesterday the establishment of the Sub-Faculty of Translational Medicine and Public Health, and the appointment of Professor Stephen Jane, Head of Central Clinical School (CCS) as Foundation Dean of the Sub-Faculty.

Cancer drug developer wins award for Monash-initiated protein research

Professor Stephen Jane first discovered
the importance of the enzyme PRMT5

by Anne Crawford

Melbourne-based drug developer Cancer Therapeutics CRC (CTx) has received a sought-after award in recognition of its work on novel oncology drug candidates, based on early research conducted at Monash University.

CTx received the Cooperative Research Centres (CRCs) Association’s Award for Excellence in Innovation, presented at the Association’s annual awards dinner at Parliament House in Canberra on 24 May.

Ancient gene involved in spina bifida also plays a role in motor coordination and anxiety

A/Prof Stephen Ting

by Anne Crawford

Curiosity and a compelling hypothesis prompted clinician and haematology researcher, Associate Professor Stephen Ting, to revisit the subject matter of his PhD a decade later. The findings of his recent study into the transcription factors of an ancient gene family known as the Grainyhead-like (Grhl) genes have revealed more than he expected and may have implications for future neuroscientific research.

Mutation find may help leukaemia patients

Dr Cedric Tremblay (right) with a co-author,
PhD student Dr Sung Kai Chui.  The
research group has identified a cancer
promoting mutation. See paper.

by Anne Crawford

Researchers from Monash University’s Australian Centre for Blood Diseases (ACBD) have become the first scientists to describe the mechanisms by which a recently identified mutation makes leukaemia cells more aggressive. Their work is progressing in preclinical trials that may lead to the development of a drug to help treat patients with T-cell acute lymphoblastic leukaemia (T-ALL) who are resistant to conventional chemotherapy.

Video of the week: Prof Steve Jane at the 2016 AMREP Honours night

Prof Steve Jane on why Honours at AMREP and what translational research is at the 16 Aug 2016 AMREP Honours and graduate research information night. Steve presented along with PhD student Angela Nguyen and Honours coordinator Dr Justin Hamilton for CCS. We will be posting all videos in a playlist. About 180 students attended the evening.

See more:

• Honours at AMREP: www.med.monash.edu.au/cecs/education/honours.html 
• Video: www.youtube.com/watch?v=a_lhKBfJuYQ

Video of the week: Translational research at Monash University

What is translational research? Monash University's three heads of its metropolitan based clinical schools talk about translational medical research, how it works, why Monash is equipped to deliver it so well and the support offered to graduate students starting out on this career path. Prof Eric Morand is Head of School of Clinical Sciences at Monash Health, Prof Stephen Jane is Head of Central Clinical School and Prof Ian Davis is Head of Eastern Health Clinical School. See more:

• Translational Research education: www.med.monash.edu.au/cecs/education/translational/
• Central Clinical School: www.med.monash.edu.au/cecs/ 
• Eastern Health Clinical School: www.med.monash.edu.au/ehcs/ 
• School of Clinical Sciences at Monash Health: www.med.monash.edu.au/scs/

Photo of the week: Epidermal/Development Lab group

2016 Epidermal/Development Lab group. L-R: Dr Marina Carpinelli, Mr Michael de Vries (PhD student), Dr Lee Miles, Dr Seb Dworkin, Dr Charbel Darido, Ms Lakshmi Krishnan, Ms Alana Auden, Dr Smitha Georgy. Absent: Prof Steve Jane, Mr Darren Partridge

The Epidermal/Development group headed by Prof Stephen Jane welcomes Dr Lee Miles and Mr Michael de Vries. Lee is a recent Monash PhD graduate specialising in developmental gene expression regulation using the animal model of zebra fish. Michael is a PhD student who started in 2015. His thesis topic is "The role of Grainyhead-like transcription factors in craniofacial development". See more about the group's research at www.med.monash.edu.au/medicine/alfred/research/epidermal-development.html

Identification of a mutation in red blood cells that can worsen sickle cell disease

By Dr Jodie Abramovitch

Sickle cell disease (SCD) is a genetic condition in which red blood cells (RBC) have an abnormal bowed or sickle shape due to a mutation of haemoglobin. These RBC are unable to travel well through small blood vessels, often becoming trapped and subsequently dying. This leads to a low red blood cell count (anaemia) which is why this disease can also be known as sickle cell anaemia. The trapped RBC can lead to occlusion of blood vessels leading to lack of oxygen and tissue death in many organ systems - producing extreme pain and organ failure.

L-R: Dr Fiona Brown, Prof. Stephen Jane,
Ms Loretta Cerruti, A/Prof David Curtis

RBC require electrolytes such as potassium (K) and chloride (Cl) to function properly. These electrolytes are actively moved in and out of cells by proteins called co-transporters. The K-Cl co-transporter, therefore, moves K and Cl along with water in and out of RBC to control cell size.

A recent study by researchers from the Australian Centre for Blood Diseases (ACBD), led by Associate Professor David Curtis and Professor Stephen Jane with collaborators from the Florey Institute and Walter and Eliza Hall Institute, identified a mutation within a K-Cl co-transporter known as Kcc1 in a mouse model. This mutation increased the activity of the K-Cl co-transporter leading to smaller RBC.

When the mutation in Kcc1 was introduced into a mouse model of SCD that mimics human disease, it was shown that disease was worsened. A higher proportion of RBC were sickle shaped which led to blocked small blood vessels and more extensive tissue damage. It was concluded that the mutation in Kcc1 was directly linked to a more serious presentation of SCD.

This research highlights the potential therapeutic use of targeting K-Cl (and other electrolyte) co-transporters to inhibit their activity in diseases such as SCD. 

Reference: Brown FC, Conway AJ, Cerruti L, Collinge JE, McLean C, Wiley JS, Kile BT, Jane SM, Curtis DJ. Activation of the erythroid K-Cl cotransporter Kcc1 enhances sickle cell disease pathology in a humanized mouse model. Blood. 2015 Dec:126;2863-70. 

doi: 10.1182/blood-2014-10-609362

Monash discovery central to record-breaking licensing deal

Professor Stephen Jane, Head of Central
Clinical School, Monash University

A suite of drugs developed by the Cancer Therapeutics Cooperative Research Centre (CTx) from early Monash research has just been licensed to global healthcare leader MSD, known as Merck in the US and Canada, in what is believed to be one of the largest preclinical licensing deals involving an Australian discovery.

The drugs – which are inhibitors of protein arginine methyltransferase 5 (PRMT5) – have potential clinical applications in both cancer and non-cancer blood disorders.

The importance of PRMT5 was first discovered by Professor Stephen Jane, Head of the Monash Central Clinical School, who initiated the search for inhibitory drugs.

CCS successes in 2015 NHMRC funding

Asian Scientist Magazine profiles CCS Translational Research

Asian Scientist Magazine has profiled the Monash Translational Research programs for its readership in all corners of Asia, including China, India, South Korea, Japan and Australia.

“Our motivation for establishing the program centered on three core tenets: the increasing importance of translational research at both government and community level; the lack of specific training in translational research for our post-graduate students; and the ever shrinking career opportunities offered by government-based fellowship schemes in Australia,” said Professor Stephen M. Jane, head, of the Central Clinical School at Monash University.

“The courses have been specifically designed to meet an emerging market need for scientists and clinicians to be trained in the development of basic research findings through commercial­ization and regulation of therapeutic products in multi­disciplinary environments.”

Read full article from Asian Scientist Magazine at: http://www.asianscientist.com/2015/08/academia/monash-launches-translational-phd-program/

Publication: Grhl1 gene influences heart rate, not blood pressure

Image: www.livescience.com

The Grainyhead-like 1 (GRHL1) transcription factor is tissue-specific and is very highly expressed in the kidney. In humans the GRHL1 gene is located at the chromosomal position 2p25. A locus conferring increased susceptibility to essential hypertension has been mapped to 2p25 in two independent studies, but the causative gene has never been identified. Furthermore, a statistically significant association has been found between a polymorphism in the GRHL1 gene and heart rate regulation. The aim of our study was to investigate the physiological consequences of Grhl1 loss in a mouse model and ascertain whether Grhl1 may be involved in the regulation of blood pressure and heart rate. Our work did not discover any new evidence to suggest any involvement of Grhl1 in blood pressure regulation. However, we determined that the loss of Grhl1 influences the regulation of heart rate in a mouse model.

Reference: Pawlak M, Walkowska A, Mlącki M, Pistolic J, Wrzesiński T, Benes V, Jane SM, Wesoły J, Kompanowska-Jezierska E, Wilanowski T. Consequences of the loss of the Grainyhead-like 1 gene for renal gene expression, regulation of blood pressure and heart rate in a mouse model. Acta Biochim Pol. 2015;62(2):287-96. doi: 10.18388/abp.2015_1001. Epub 2015 Apr 21.

30 Sep: Translational Research symposium and Dept Medicine 50th anniversary

L-R: James Rankin and Barry Firkin, USyd MBBS
graduates, who both went on to become leaders in
their chosen medical fields. Barry was the inaugural
head of the Monash Dept of Medicine at the Alfred.

Translational Research Symposium and Department of Medicine 50th anniversary

"Translational Research" - what does it mean? The short answer is a speeding up of basic findings in medical research into clinical practice, without any compromise of research quality. You are invited to attend this day's program, which features speakers from across the continuum, giving case studies on what has worked best to expedite discovery to application.

About the Department

The Monash Department of Medicine was established in 1965, with Professor Bryan Hudson as Foundation chair. The Department at the Alfred started in 1968 under the leadership of Professor Barry Firkin, who was succeeded in 1992 by Professor Nip Thomson AM. Professor Stephen Jane became Head of the Department of Medicine and Head of Central Clinical School in 2011.

Details

• Date: Wednesday, 30 September 2015
• Time: 8.00 am registration for 9.00 am start. See program below for detail of the day's timetable
• Venue: AMREP Lecture Theatre, adjacent to the BakerIDI Institute at 85 Commercial Road, Melbourne 3004, 200 metres east of the main Alfred Hospital entrance. See map.
• Cost: Free
• RSVP by Friday 25 September for catering purposes
• Enquiries: Catherine.Wong@monash.edu ph +61 3 9903 0640

Monash research on head and neck cancer provides first real breakthrough in decades

The research group which published this paper. L-R: Dr Charbel
Darido, Ms Seema Srivastava, Mr Michael Cangkrama, Prof
Stephen Jane, Dr Smitha Georgy, Dr Seb Dworkin, Ms Alana
Auden. Not present: Dr Darren Partridge, Prof Catriona McLean

Research published this week in the prestigious Journal of the National Cancer Institute provides the first real insight in more than 50 years as to how head and neck cancers – one of the more deadly forms of cancer – develop. The discovery opens the way to identifying patients with particular types of head and neck cancer that may be candidates for more targeted therapies.

Research: Grainyhead gene works to regulate heart rate

Consequences of the loss of the Grainyhead-like 1 gene for renal gene expression, regulation of blood pressure and heart rate in a mouse model.

The Grainyhead-like 1 (GRHL1) transcription factor is tissue-specific and is very highly expressed in the kidney. In humans the GRHL1 gene is located at the chromosomal position 2p25. A locus conferring increased susceptibility to essential hypertension has been mapped to 2p25 in two independent studies, but the causative gene has never been identified. Furthermore, a statistically significant association has been found between a polymorphism in the GRHL1 gene and heart rate regulation. The aim of our study was to investigate the physiological consequences of Grhl1 loss in a mouse model and ascertain whether Grhl1 may be involved in the regulation of blood pressure and heart rate. Our work did not discover any new evidence to suggest any involvement of Grhl1 in blood pressure regulation. However, we determined that the loss of Grhl1 influences the regulation of heart rate in a mouse model.

$5.4M Wellcome Trust grant for blood disorder therapeutic development

CCS researchers involved in understanding the biology
underpinning the therapeutic development.
L-R: Dr Fiona Brown, Dr Stefan Sonderegger, A/Prof David
Curtis, Prof Stephen Jane, Ms Loretta Cerutti.
Absent: Dr Emma Toulmin

$5.4 million funding will allow Monash researchers to develop novel approaches to treat major blood disorders, by switching on a form of haemoglobin normally only utilised by babies before birth.

Molecular pathways for skin formation

Michael Cangkrama, who has recently
completed his PhD on skin formation

The skin is the body’s largest organ. It forms in utero and is maintained throughout adult life. However, the womb is a more stable and regulated place than the more complex terrestrial environment, and skin function in an embryo and an adult is very different.

What are the molecular mechanisms contributing to the development, regulation and maintenance of the skin structure in utero and post-natally? Why are they different? It comes down to highly conserved genes, largely unchanged from fruit fly to human. These three genes (in mammals) are members of a family of transcription factors known as the Grainy head-like (Grhl) transcription factors that play a role in organ (including skin) development and barrier repair after tissue damage. Grhl1 and 3 are both highly expressed in skin.

Australian Academy of Health and Medical Sciences Fellowships for AMREP researchers

Recently elected AAHMS Fellows at the ceremony in Canberra 25 March 2015

The Australian Academy of Health and Medical Sciences (AAHMS) was established in 2014 with the aim of influencing the health and medical scientific and policy landscape of Australia. Its three broad aims are:

• Mentoring the next generation of clinician researchers.
• Providing independent advice to government and others on issues relating to evidence based medical practice and medical research.
• Providing a forum for discussion on progress on medical research with an emphasis on translation of research into practice.

Congratulations to all the Alfred Medical Research and Education Precinct (AMREP) based researchers recently elected as Fellows.

• Prof Jamie Cooper (Monash/Alfred)
• Prof Mark Cooper (Baker IDI/Alfred)
• Prof Brendan Crabb (Burnet)
• Professor Suzanne Crowe (Burnet/Alfred)
• Prof Stephen Jane (Monash/Alfred)
• Prof Garry Jennings (Baker IDI/Alfred)
• Prof David Kaye (Baker IDI/Alfred)
• Prof Bronwyn Kingwell (Baker IDI)
• Prof Paul Myles (Monash/Alfred)
• Prof Robyn O’Hehir (Monash/Alfred)
• Prof Jeffrey Rosenfeld (Monash/Alfred)
• Prof Jonathan Shaw (Baker IDI) 
• Prof John Zalcberg (Monash)

See more about AAHMS: www.aahms.org/

Medical research graduates to be more industry oriented: Prof Stephen Jane

Prof Stephen Jane: The gap between
medical industry and research can be
bridged more effectively with training.

The Australian Financial Review (AFR) published an opinion piece (23 Feb 2015) by Professor Stephen Jane on the need for medical graduates to think beyond academia for their future career paths, and describing Monash University's new Translational Research PhD and graduate certificate. "This new educational stream offers scientists and clinicians an opportunity to develop skills specifically aimed at getting basic research to practical outcomes - in clinical practice, biotech and pharma, commercialisation, medical devices and regulation - in multidisciplinary environments." See more:

• AFR link (paywalled)
• Translational Research PhD and graduate certificate

New efforts to broaden PhD training are “fantastic” but Australian medical industry needs capitalisation

Fabienne Mackay says the medical industry hasn’t
been supported enough.
Picture: Aaron FrancisSource: News Corp Australia

The Australian published an article (18/2/2015) quoting Professors Stephen Jane and Fabienne Mackay on medical research PhD training and post PhD opportunities. Link. Excerpts quoted below.

"Monash University’s Central Clinical School head, Stephen Jane, said the new PhD ... included content on intellectual property, designing clinical trials and statistics. He said the PhD would arm students with 'a skill set commensurate with a far broader range of career options but also emphasise the necessity to engage with industry'.

"...for leading medical researcher Fabienne Mackay, head of the department of immunology at Monash University, the real problem is that Australia’s medical industry hasn’t been supported enough to grow to the scale the country needs to capitalise on its strong medical research. She said the US was also facing an oversupply of medical researchers but, unlike Australia, there was a big medical industry to soak them up.

“'The real problem does not come from universities who develop links with national and international industry partners to create opportunities for their students and the workforce. The problem is the choice made by leaders of this nation who have neglected efforts to diversify our economy and never made the choice to exploit homegrown talents to build a decent homegrown medical industry,' she said."