Dr Joanne Reed is on a mission – to track down the immune cells that ‘go rogue’ in people with Sjogren’s syndrome and systemic lupus erythematosus (lupus). In autoimmune disorders such as these, immune cells, called B cells, start to produce antibodies against the body’s own tissues, instead of against invaders.
Dr Reed’s work has today been given a significant boost, with the award of a New Investigator Project Grant from the National Health and Medical Research Council. Worth over $900,000 over 4 years, the grant will support Dr Reed’s search for rogue B cells, and the self-reactive antibodies they produce, in patients with lupus and Sjogren’s. She is seeking to understand how rogue B cells differ from their healthy cousins – and ultimately to develop new therapies that target rogue cells, but leave healthy immune cells untouched.
Dr Reed’s project is one of 19 at Garvan to attract NHMRC Project Grant funding in the 2017 funding round. Together, the 19 grants will drive research across all six of Garvan’s research Divisions, including research into breast, prostate and pancreatic cancer, neuroblastoma, cancer immunotherapy, diabetes, obesity, autoimmune disease and other immune disorders, and the diagnosis of genetic disorders.
Garvan’s Project Grants together comprise $13.5 million in NHMRC funding, and reflect a 30% success rate, the second highest success rate in Australia. Garvan has received a total of $16.1 million in this funding round, with an additional $2.6 million announced in October.
Professor John Mattick, Garvan’s Executive Director, says, “I’m delighted at the wide range of Garvan’s projects that have been supported by the NHMRC today, and at the high success rate that has been achieved across all six of our research Divisions. I congratulate the talented and driven Garvan researchers – and medical researchers across the country – whose projects have been funded.
“Inevitably, there are outstanding projects with great translational potential that have not achieved funding this time. These projects are very important and we will keep working hard to find alternative sources of funding to support the researchers driving them.”
The successful projects are:
Multiple myeloma: Researchers will test new approaches to eradicating the cancer cells that ‘sleep’ in bone in this cancer, and ultimately cause relapse when they ‘wake’ – Prof Peter Croucher (Bone Biology Division) and Dr Tri Phan (Immunology Division), with Prof Andrew Zanettino (University of Adelaide) and Prof Ido Amit (Weizmann Institute of Science, Israel)
Mevalonate kinase deficiency: The research team will work towards a deeper understanding of this potentially fatal autoinflammatory disease of children, with the aim of identifying therapies that treat the underlying cause of disease and not merely its symptoms – Prof Mike Rogers (Bone Biology Division) and Dr Elissa Deenick (Immunology Division), with A/Prof Anna Simon (Radboud University, Netherlands)
Breast cancer: Dr Liz Caldon (Cancer Division) seeks to uncover new insights into late-recurring estrogen receptor positive breast cancer, which is resistant to therapy. Dr Caldon will explore whether primary breast tumours contain a population of ‘therapy tolerant’ cells that re-emerge in recurrent cancer.
Pancreatic cancer: Researchers will explore new ways to ‘prime’ pancreatic cancer ahead of chemotherapy, an approach that seeks to making chemotherapy more effective by targeting the tissue surrounding the tumour itself – Dr Thomas Cox and A/Prof Paul Timpson (Cancer Division)
High-risk neuroblastoma: The research team will explore new approaches to therapy for this aggressive brain cancer of childhood. They will follow up on recent findings that many neuroblastomas contain a defect in a key signalling pathway (Jnk) that means that existing therapies will be ineffective – Dr David Croucher and A/Prof Alex Swarbrick (Cancer Division), with Prof Walter Kolch (University College Dublin, Ireland) and Jamie Fletcher (Children’s Cancer Institute)
Pancreatic cancer: Using cutting imaging technology and 3D models that mimic pancreatic cancer, researchers will explore how individual patients with pancreatic tumours differ in their response to chemotherapy. They will seek to overcome poor drug response and to test the potential of a promising combination therapy – A/Prof Paul Timpson and Dr Marina Pajic (Cancer Division), with Dr Jennifer Morton (Beatson Institute for Cancer Research, Glasgow) and A/Prof Yingxiao Wang (UC San Diego, USA)
Triple-negative breast cancer: Few treatments target this aggressive form of cancer. Garvan’s researchers will investigate whether the protein JNK, which has a wide range of cancer-promoting functions, could be a drug target in triple-negative breast cancer – Dr David Croucher and Dr Thomas Cox (Cancer Division)
Type 2 diabetes: A/Prof Ross Laybutt (Diabetes and Metabolism Division) seeks to uncover new ways to protect against type 2 diabetes, by exploring the underlying mechanisms that govern whether the cells that produce insulin succeed – or fail – in maintaining blood glucose at healthy levels.
Diabetes (types 1 and 2): In diabetes, cells in the pancreas fail to produce enough insulin to keep blood sugar in check. Garvan researchers have recently uncovered a new signalling pathway that may be key to unlocking significant insulin release. In this project, the team will explore the pathway and how it is regulated – Dr Yanchuan Shi and Professor Herbert Herzog (Neuroscience Division) and A/Prof Ross Laybutt (Diabetes and Metabolism Division)
Obesity: Professor Herbert Herzog (Neuroscience Division) will investigate newly discovered subpopulations of brain cells that have a role at determining appetite and whole-body energy balance, with the aim of new targets for therapy.
Genetic disorders: The research team will develop new types of Sequins (‘mirror’ DNA sequences) that can be added to genome sequencing reactions to improve the diagnosis of genetic disorders – A/Prof Marcel Dinger, A/Prof Tim Mercer and Dr James Blackburn (Genomics and Epigenetics Division), with Professor Leslie Burnett.
Epigenetic changes in prostate cancer: The research team will extend their work on a DNA packaging protein, testing how it affects the 3D organisation of DNA in cells. They will look closely at prostate cancer cells to uncover how the modified protein affects the expression of key genes – Prof Susan Clark and Dr Fatima Valdes Mora (Genomics and Epigenetics Division)
DNA organisation in cancer: Researchers will look closely at the ‘architectural’ protein CTCF, which is key to the 3D organisation of DNA of cells. They will uncover new insights about how CTCF functions, and the effect of its malfunction in cancer cells – Prof Susan Clark and Dr Clare Stirzaker (Genomics and Epigenetics Division)
Immune disorders: Researchers will explore the role of Th9 cells: newly discovered cells in the immune system that help defend us from infection, but are also involved in allergy, inflammatory bowel disease and cancer – Dr Cindy Ma and Dr Elissa Deenick (Immunology Division)
Immune disorders: The immune system must be tightly regulated to ensure that it can effectively fight off infection, yet avoids autoimmunity, inflammation or allergy. In this project, Dr Elissa Deenick and Dr Cindy Ma (Immunology Division) will study patients who have genetic variants that affect their immune systems, to reveal some of the critical signals that maintain immune control.
Immunodeficiency: In autoimmune disorders such as lupus, the body’s immune system attacks ‘self’. To unlock new understanding of these disorders, the research team will study how the immune system malfunctions in patients with a newly uncovered gene variant, which leads to autoimmunity but also to recurrent infections – Dr Tri Phan and Dr Cindy Ma (Immunology Division), with Dr Melanie Wong (Children’s Hospital at Westmead)
Autoimmune disease (see above): Dr Joanne Reed and Dr Katherine Jackson (Immunology Division) will seek to identify the ‘rogue cells’ in patients with lupus and Sjogren’s syndrome, which are thought to drive the immune system to attack ‘self’.
Cancer immunotherapy: Immunotherapies, which stimulate the immune system to attack cancer, are transforming the treatment of many cancers. The research team will explore the mechanism of action of ‘IL2 superkines’, a new class of immune-activating drugs – A/Prof Daniel Christ, Prof Jonathan Sprent and A/Prof Cecile King (Immunology Division)
Cancer immunotherapy: Prof Jonathan Sprent (Immunology Division) will investigate a new approach to making cancer immunotherapy more effective. The project explores whether tiny ‘nanovesicles’ can drive the immune system to attack cancer more powerfully.