2024 AIPS Florey Next Generation Award Winner
Luis Garcia Marin
QIMR Berghofer Medical Research Institute
Luis’s research in neuroimaging genetics aims to uncover how our genes, brain structure, behaviour, and mental health are interconnected. By using advanced statistical modelling and machine learning on large genetic, brain imaging, sleep, and mental health datasets, Luis seeks to identify the biological mechanisms that influence brain structure and the risk of mental health conditions. Understanding which genes are involved in these variations is crucial for developing targeted therapies and personalised treatments.
In a landmark study, Luis led the analysis of the largest research project on the genetic basis of brain and skull size. This study included about 75,000 participants and 200 researchers worldwide. They identified 254 genetic variants and several genes that affect brain shape and size. This research, soon to be published in Nature Genetics, highlights how specific genes in particular cells influence brain development and genetic susceptibility to neurological and psychiatric disorders.
Luis is also developing polygenic risk prediction methods to assess disease risk based on an individual’s genetic profile. These methods can screen large populations to identify people at higher risk for certain disorders, allowing for early intervention and prevention. Additionally, by identifying genetic similarities across various mental health conditions, we can uncover common molecular pathways and symptoms shared by these disorders. This could lead to the development of multi-purpose drugs and better treatment options.
In another project, published in The Journal of Headache and Pain, Luis discovered new genetic variants linked to migraines. He then used this information to discover novel causal risk factors for migraines and headaches. This work was recognised by the European Headache Federation by way of a 2021 Enrico Greppi Award.
Luis’s research aims to bridge the gaps between genetics, neuroscience, and medicine. By understanding how our genes impact brain structure and mental health, we can improve prevention, screening, diagnosis, and treatment for neurological and psychological conditions, ultimately enhancing patient care for people living with these disorders.
2024 Florey Next Generation Finalists
Dr Yin Yuan
WEHI
Acute myeloid leukaemia (AML) is the most deadly blood cancer and is diagnosed in >1000 Australians of all ages every year. With current therapy, including intensive chemotherapy and bone marrow transplants, fewer than 40% of people diagnosed will be alive 5 years later. The most lethal form of AML carries a mutation in the gene TP53, making these leukaemias even more poorly responsive to our usual treatments. Indeed <10% of people diagnosed with TP53-mutated AML are alive two years after diagnosis. It is this problem that Dr Yin Yuan is tackling.
Her work builds on advances made recently with the introduction of venetoclax into routine practice. Venetoclax is the first of a new class of targeted anti-cancer drug that works by inhibiting a key protein called BCL2. Because BCL2 is important for leukaemia cells to stay alive, the action of venetoclax causes leukaemia cell to die. Venetoclax has doubled the survival rates at 2 years after diagnosis for many adults with AML, representing the most dramatic improvement in care for AML in the last 50 years. While giving real hope to many, this drug has only modestly improved outcomes for people diagnosed with TP53-mutated AML.
To tackle TP53-mutated AML, Dr Yuan sought a drug that would both kill AML cells on its own and work even better when combined with venetoclax. Building on research by colleagues at WEHI, Dr Yuan tested STING agonists for the ability to kill AML. STING agonists were known to stimulate the immune system, but they discovered that these drugs can also kill some cancers directly. Dr Yuan’s results in AML were quite astonishing.
STING agonists induced leukaemia cells to die, whether the TP53 gene was normal or mutated. STING agonists also killed leukaemia cells that were resistant to venetoclax. Combining STING agonists with venetoclax was highly effective against the majority of AMLs from a large cohort of patients. Based on these results Dr Yuan and colleagues are planning to conduct early phase clinical trials in AML patients with STING agonists alone and in combination. This is ground-breaking research, with real potential to improve outcomes.
Dr Yuan’s work was published in the prestigious journal, Cancer Cell, attracting television and print media attention. She is joint first author on the paper and conducted all the AML research. She has also presented this and subsequent work at major conferences in Australia, USA and Europe, winning multiple awards.
Chelsea Mayoh
Children’s Cancer Institute
Chelsea Mayoh is a 3rd year PhD candidate at the Children’s Cancer Institute. She focuses on integrating complex data derived from the characterization of the molecular features of childhood cancers into a comprehensive understanding of the fundamental nature of paediatric cancer, both at a cohort level and of each individual cancer. Chelsea’s research is an integral part of the ZERO childhood cancer program (ZERO). ZERO deploys the molecular characterisation of childhood cancer samples to identify novel treatment options that would otherwise go unrecognized. Chelsea constructed the analytical pipelines to interrogate the molecular data, and developed algorithms that integrate this analysis across all the molecular platforms. This is the computational bedrock that has driven the remarkable achievements of the ZERO program. These include identifying the molecular changes driving a cancer in 94% of patients and generating novel treatment recommendations in 72%. Chelsea is co-first author on the Nature Medicine paper (PMID:33020650) highlighted as one of the Top 10 Scientific Achievements in Clinical Genomics (PMID: 34861172). Most recently, in Nature Medicine, ZERO has shown that the therapeutic recommendations driven by genomic analyses dramatically improves survival of high-risk childhood cancer (PMID: 38844796).
Chelsea Mayoh has made other exciting and novel genomic discoveries during her PhD. Pre-clinical drug testing (testing potential therapies directly against cancer cells ex vivo) is a novel program that adds to the genomic analyses of tumours. She developed the computational pipelines that identify drug sensitivities to provide an alternate pathway to potentially effective treatments. Chelsea is first author on this work published in Cancer Research (PMID:37523146). Chelsea also drove the development of a paediatric cancer specific signature of inflammation (T-cell infiltration) revealing that many more childhood cancers harboured immune cells than previously suspected (PMID:37013636). This signature is now part of the clinical reporting in ZERO and more importantly, in collaboration with the Canadian precision medicine program (PROFYLE), this immune signature has been incorporated into a clinical trial (OPTIMISE) of immune combination therapy in children. Chelsea has led the Australian arm of this collaboration.
Chelsea has published as first author in Nature Medicine, Genome Biology, Cancer Research and Scientific Reports, and as a co-author in 17 other manuscripts. She has been an invited speaker at national and international conferences (e.g. REACT4KIDS, ANZCHOG Cellular Therapies). Her work has been critical to the clinical impact of ZERO, the most transformational program in childhood cancer research in decades.
Florey Next Generation Award Winner
Chloe Yap
Mater Research
Chloe Yap is a final year MD-PhD-GCBusLead candidate at the Mater Research Institute and the Institute for Molecular Bioscience, University of Queensland. Her doctoral thesis integrates deep phenotypic and multi-omics data (genetic, epigenetic, gut metagenomic and blood metabolomic) from the Australian Autism Biobank, working with the Autism CRC answer under-researched questions of specific interest to autistic people.
This approach has contributed to a more comprehensive understanding of autism biology and its commonly co-occurring conditions. Chloe’s PhD has also included a stint at UCLA on a Fulbright Future Scholarship to investigate the contribution of brain cell-types to neuropsychiatric diagnoses. She is also a keen advocate for translational research and the clinician-scientist pathway.
Ultimately, Chloe hopes to unify her interests in psychiatry, medicine, bioinformatics, health systems and policy to improve the physical wellbeing of people living with mental health conditions.
2022 CSL Florey Next Generation Finalists
Jack Chan
Peter MacCallum Cancer Centre
Jack is a final year PhD candidate undertaking research at the Peter MacCallum Cancer Centre with Beavis and Darcy Laboratories. He is part of a research group that aims to enhance a specialised cancer therapy known as chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumours.
Jack is a high-performing candidate having published several papers in leading journals such as Nature Immunology and Cell Press and has received a number of awards including the prestigious Campion Ma Playoust Memorial Award. Jack is passionate about medicines access and has a keen appreciation for science communication.
In his spare time creates video content for research adjacent departments at PeterMac and runs a small podcast for general audiences. Following completion of his PhD, Jack has aspirations to transition into a role in field medical affairs.
Jose Alquicira Hernandez
Garvan Institute of Medical Research
Jose Alquicira Hernandez is an Early Career Researcher at the Garvan Institute of Medical Research. During his PhD, he pioneered statistical and computational methods for single-cell genomics and applied statistical genetics approaches to study the genetic basis of autoimmune disease in the Australian population. His work has been published in 11 high-impact papers including Science, Nature Genetics, and Genome Biology and has been cited more than 1200 times. Jose is one of the scientific leaders of the single-cell eQTL consortium, the largest international effort to characterize the effect of genetic variation in gene expression.
Due to his research impact, Jose recently received an NHMRC Investigator grant to study the impact of genetic variation in the human immune system and its role in disease.
Additionally, he was invited and financially supported to run a workshop on immunogenomics at the Stanford University School of Medicine and the School of Medicine of UCSF in 2019. This year, Jose established a long-term collaboration with the Harvard Medical School, where he was invited to visit and present his work on immunogenomics. Jose is currently undertaking a fully-funded research stay at the Helmholtz Institute of Computational Biology in Germany where he is applying machine and deep learning approaches to understand autoimmune cell dynamics.