Like any far-reaching and ambitious medical research initiative, the Garvan-Weizmann partnership relies heavily on support and investment from generous and forward-thinking individuals and organisations.
Vital initial investment from the NSW Government, Mr John Roth and Ms Jillian Segal AM, Mr and Mrs Laurie and Di Sutton and Mr Johnny Kahlbetzer has funded the construction of the Garvan-Weizmann Centre for Cellular Genomics.
Collaborative research projects
We are delighted to introduce five inaugural research projects – all existing collaborations between Garvan and Weizmann researchers – that mark just the beginning of the research program within the Garvan-Weizmann partnership.
Towards personalised medicine for pre-diabetes
Researchers from Garvan and the Weizmann Institute are working together to understand how different types of pre-diabetes can be distinguished in patients — with the aim of improving treatment and stemming the global epidemic of type 2 diabetes.
“Previously, it hasn’t been possible to identify the different forms of pre-diabetes, or to tailor treatments to specific patients — but our study proposes to change that,” says Dr Dorit Samocha-Bonet.
In the first instance, the study will recruit 150 volunteers. Researchers will measure a host of parameters including body fat, liver fat, blood parameters, physical activity, sleep patterns, diet and —importantly — the individual’s genome sequence and the genome sequence of gut microbes, which gives a readout of each individual’s ‘microbiome’.
Participants will then receive one of three randomised treatments. The study will measure treatment success by comparing patterns of glucose levels in the blood before and after the treatments.
Researchers will next develop algorithms that predict a pre-diabetic individual’s response to treatment, and trial their predictive power in a separate smaller cohort of 45 individuals with pre-diabetes.
The study will leverage Garvan’s considerable expertise in the measurement of metabolic readouts in people at its Clinical Research Facility; and the Weizmann Institute’s remarkable track record in uncovering how our ‘microbiome’ affects our metabolic response.
“Ultimately, we hope to make it possible to readily identify an individual’s pre-diabetes subtype in order to guide an optimal treatment to prevent diabetes,” says Dr Samocha-Bonet.
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.
Towards personalised medicine in melanoma: who will respond to immunotherapy?
he Garvan-Weizmann partnership will play an important role in the melanoma research of Professor Yardena Samuels (Weizmann Institute). Professor Samuels is working to understand how melanomas vary between individuals, with the aim of predicting which cancers will respond to immunotherapy.
Immunotherapies — which ‘turn on’ the immune system and empower it to attack tumours — are currently at the forefront of revolutionary cancer treatment. Immunotherapy based on the body’s T cells (a type of white blood cell involved in the body’s immune system), has achieved remarkable results in some melanoma patients, yet most patients still fail to respond to T cell-mediated immunotherapy, and little is understood about why.
Professor Samuels and her colleagues have already developed a remarkable tumour bank containing samples from melanoma patients who have been treated with immunotherapy. Built specifically for the study of melanoma immunogenomics, the tumour bank makes it possible to explore the processes by which tumors evolve to actively escape the defensive mechanisms of the immune system, and to identify ways to reactivate tumour-specific T cells in melanoma.
Professor Samuels, alongside Dr Andrew Stone from Garvan, will perform whole genome sequencing and RNA sequencing on 80 melanoma samples (half of which responded to immunotherapy, and half which did not) from the tumour bank. This will allow them to identify the mutations and changes in gene expression that may be linked to the disease.
Ultimately, the researchers aim to provide tools for predicting how melanomas will respond to treatment, making it possible to tailor immunotherapies to individual patients and tumours.
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.