In only a few short years, the Centre has embarked on a range of research programs, both nationally and internationally.
Under the broader themes of immune profiling, stem cell modelling and cancer clone therapeutics; researchers are using cellular genomics to study the genetic risk of disease across cell development stages, find ‘cancer causing’ cells in tumour environments and the genetic variants that may cause immune disease.
Collaborative research projects
Cancer Cell Therapeutics
Recent years have seen significant advances in the understanding of cancer through improvements in cell sequencing and computational technology. However, challenges still existed in designing an approach that is powerful enough to profile complex systems such as those seen in blood cancer patients.
Until recently, it was not possible to accurately identify cancer-causing cells in a tumour, or their effects on cell ‘fitness’.
At the Garvan-Weizmann Centre of Cellular Genomics, we have now developed methods to identify these cells.
This method will enable us to identify which cells will respond to different treatment options and explore how new immunotherapies can be designed to reprogram patient’s immune cells. Using this information, the aim of the program is to help support the development of new drugs that are cancer cell specific, as well as creating clinical management strategies that enable cancer patient’s cell-types to be identified. This information will then inform the best treatment option in the push toward personalised medicine.
The team have validated this methodology from initial work looking at skin cancer, lung cancer, and head and neck cancer, proving the hypothesis that clonal cells can be identified, and that patients’ immune cells will attach or ignore different clones. From here, the research project will expand and include:
- Gastrointestinal interstitial tract cancer
- Lung cancer
- Breast cancer
- Brain cancer
- Prostate cancer
- Head and neck cancers
- Skin cancer
- Pancreatic cancer
- Adrenal cancers.
Hope Research: finding hope for autoimmune disease
Researchers at the Garvan and Weizmann Institutes have uncovered evidence that there is a common cause of autoimmune diseases, a cell in the immune system that has gone ‘rogue’. To keep up with invading viruses and bacteria, which rapidly mutate to evade detection and destruction, the cells of our immune system must change just as quickly.
‘Bad mutations’ are an inevitable result of these rapid changes, with these cells more likely to multiply and form a rogue clone in response to the body’s own tissues.
Hope Research is a revolutionary approach to tackle not one, but over 40 autoimmune diseases. Using cutting‑edge
cellular genomic technology in the Garvan‑Weizmann Centre for Cellular Genomics, researchers will identify the
rogue clones in a range of seemingly unrelated autoimmune diseases including Multiple Sclerosis, CREST, type 1 diabetes,
Sjögren’s syndrome, inclusion body myositis, Crohn’s disease, psoriatic arthritis and rheumatoid arthritis.
These studies will pinpoint chinks in the armour of the rouge clones that could make them susceptible to new forms
of immunotherapy, or to new drugs that target specific immune cell pathways.
Read more about Hope Research and how you can support us.
OneK1K is a pioneering study that is demonstrating how genetics contribute to the risk of immune disease at a cellular level. Using the ground-breaking technology of the Garvan-Weizmann Centre for Cellular Genomics, we can now work towards solving one of the missing pieces of the puzzle.
By analysing 1000 cells from 1000 people, Onek1K will have an impact on three main areas: autoimmunity, immuno-oncology and haematology disease.
The study aims to identify and prioritise new drug targets for specific cell types in individual patients. This will initially enable patients to better manage their disease, but ultimately to prevent an autoimmune disease from developing altogether.
Statistical genetics has already identified over 2,000 positions in the genome where autoimmune risk variants reside. Every individual, both healthy and with immune diseases carry many of these risk variants without developing the disease.
The concept that a genetic variant exists in all cells but is only functional in certain cell types has been a problem and a hypothesis for over a decade.
The differences in the activation between different cell types remains unknown, presenting a critical problem as drugs that silence active genes need to be targeted to only the cell types where that gene is causing a problem.
OneK1K provides an unprecedented opportunity to help target drug development to individual cells – to deliver personalised medicine to people with immune diseases.
Through a major research effort, we now know that stem cells hold the potential to provide new options for tissue repair as well as rapid and cost-effective drug development.
In collaboration with leading stem cell scientists across Australia and the UK, the Garvan-Weizmann Centre for Cellular Genomics is using single cell sequencing and advanced machine learning to investigate how the genetic risk for disease varies across cell development stages. Led by Professor Joseph Powell, the team have demonstrated how the genetic risk for myocardial infarction (heart attacks) can be shown to vary across cardiac muscle cell developmental states.
There are 128 known genes associated with an increased risk of heart disease. Using cellular genomics, we can determine the stage of development of a particular cell and at what stage of development these changes result in heart disease.
To undertake this program, the team are creating a world-leading cohort of induced pluripotent stem cells (iPSCs), which can then be differentiated into many different types of human cell types, allowing them to study diseases in tissues derived from the patient. As iPSCs can be derived from any individual patient and used to recreate any tissue type from that patient, a ‘personalised’ model of disease is now possible.
Such models will facilitate improvements in disease diagnosis, increase our understanding of how disease develops and potentially allow screening for drug response. This exciting research is already being expanded to neurological diseases, blinding diseases, and kidney disease, which together affect over a million Australians.
Unleashing the potential of immunotherapies for breast cancer
“Breast cancer is the most common cancer in women — yet, for about a third of individuals with breast cancer, treatment options are very limited,” says Dr Gallego- Ortega. “So, there’s an urgent need to explore other treatment options to ensure that those individuals aren’t left behind.”
Immunotherapies, which ‘re-educate’ the immune system to recognise and destroy cancer cells, have achieved exceptional success against some types of cancers, particularly lung cancer and melanoma. In breast cancers, however, immunotherapy has been disappointing — because, in breast tumours, the immune system’s function is ‘dialed down’ and immunotherapies can’t work effectively.
The research team has already uncovered how immune function is stymied in breast cancer in preclinical models. They showed that a particular group of cells, called MDSCs (myeloid derived suppressor cells), accumulate in breast tumours and cripple immune function. Tantalisingly, the team has also shown in preclinical models that they can target and destroy MDSCs, which releases the brake on the immune system to let immunotherapies do their job.
The next step? “It’s time to investigate a similar approach in people. We will define, in unprecedented detail, the cells that make up a human breast tumour, with a particular focus on understanding MDSCs,” says Dr Gallego-Ortega.
Armed with a deep cell-by-cell understanding of human breast cancer, the researchers will explore new ways to knock out MDSCs within tumours by using antibodies that will result in the reactivation of the body’s ability to reject cancer cells. This immunotherapy approach is particularly promising for the deadly triple-negative breast cancer and familial BRCA1/2 mutation carriers.
Ultimately, they aim to identify antibodies that have the power to unleash immunotherapies and transform outcomes for breast cancer patients.
Zeroing in on the cancer cells that 'sleep' in bone
Garvan and Weizmann researchers, led by Professor Peter Croucher, Dr Tri Phan and Professor Ido Amit, are working together to solve why some cancer cells ‘sleep’ in bone for months or even years — and how their genetic output changes as they ‘wake’.
The researchers are studying multiple myeloma, a cancer of the blood in which cells lodge in bone. Already, they have isolated thousands of individual myeloma cells from bone and conducted two different kinds of single-cell analyses to measure the genetic output of a cell.
The research team has identified clusters of active genes that appear to act as ‘signatures’ of dormant myeloma cells. They are following up leads of ‘dormancy genes’ that are active in sleeping cells and so could be targeted with therapies — which could ‘force out’ and awaken dormant cells so they can be destroyed by chemotherapy.
In addition, the researchers are investigating how bone marrow biopsies could one day provide patients with a readout of their risk of relapse — which could make it possible to target therapies and treatment strategies to individual patients. Armed with knowledge that only cellular genomics can offer, the research team has — for the first time — a realistic shot at new cancer treatments, and even cures, based on eliminating or monitoring sleeping cancer cells in bone.
Hope Research: finding the ‘rogue clones’ at the root of autoimmune disease
Researchers at the Weizmann Institute and Garvan, led by Professor Chris Goodnow and Professor Ido Amit, are using cellular genomics to uncover ‘rogue clones’ of blood cells that give rise to many autoimmune diseases and blood cancers. They will identify vulnerabilities in these rogue clones to immunotherapy or other drugs, with the ultimate aim of eradicating them from the body.