Researcher profiles and projects Diamantina Institute 2020/2021 Diamantina Institute Undergraduate research MD student research The University of Queensland to focus their efforts on turning projects experience Diamantina Institute (UQDI) is a their scientific discoveries into new UQDI offers various opportunities UQ Medicine is committed to enhancing modern research facility where clinical treatments for diseases including a for undergraduate students to gain the research training and experience for and basic science are used to study variety of cancers, arthritis and other research experience in biomedical students in the Medical Program. cancer, immunolgy and genomic autoimmune diseases. research facilities including Summer and There are a number of ways students medicine. Winter research projects. UQDI focuses on bringing the can incorporate research training and The Institute has a vibrant community discoveries of basic science to the For further information visit experience into their medical degree. patient. di.uq.edu.au/study/undergraduate of over 300 researchers, students and For further information visit: support staff. We have delivered global, We aim to translate the greatest medicine-program.uq.edu.au/research/ world-changing discoveries to humanity, Summer research projects opportunities for research discoveries research-your-medical-degree such as the world’s first cervical into the cause, mechanism, prevention For further information visit: cancer vaccine. and treatment of major disease. medicine.uq.edu.au/research/research- Research higher degree strategy-and-support-office/summer- Based at the Translational Research As part of The University of UQDI is an internationally recognised research-program research facility where clinical and Institute (TRI) beside the Princess Queensland’s prestigious Faculty of medical sciences converge in the Alexandra Hospital, UQDI has strong Medicine, UQDI is committed to making Winter research projects translational research of cancer, disorders clinical interactions and world-class a global difference to health outcomes. facilities that enable researchers to be For further information visit: of immune regulation and genomic medicine.uq.edu.au/research/research- at the forefront of their fields. UQDI’s medicine. For further information visit strategy-and-support-office/winter- position within the TRI allows for a di.uq.edu.au research-projects For more information on starting a Higher much greater collaborative research Degree by Research with us, please visit: environment, allowing our researchers In July of each year UQDI offers a one medicine.uq.edu.au/future-students#qt- week course in advanced immunology. study-foundation-tabs-4 For further information visit: di.uq.edu.au/event/2293/advanced- Key research themes: immunology-course Honours program UQDI hosts honours students enrolled through other schools within the Cancer Immunotherapy Faculties of Science or Medicine at UQ or affiliated Institutions. These include (but are not limited to) the School of Chemistry and Molecular Biosciences, or Genomic medicine Skin and skin cancer the School of Biomedical Sciences at UQ. The Honours Program is a one year full time course. Students must fulfill the prerequisites of the undergraduate Immunity and Faculty/School through which they are Inflammation enrolled. For further information visit: di.uq.edu.au/study/honours Professor Gabrielle Belz Dr Anne-Sophie Bergot
Research Field Research Field Transcriptional regulation of immune cell Immunology and pathogenesis of type 1 diabetes development and memory formation in pathogen defence and mucosal immunity Research Synopsis Anne-Sophie is working with Prof. Ranjeny Research Synopsis Thomas on Immunotherapy for type 1 diabetes Our work aims to understand how the immune (T1D). system responds to infections including viruses, bacteria and parasites. We are investigating the use of a liposome based strategy to develop an antigen-specific We are investigating how different types therapy for T1D. Immunologically, it has a dual of immune cells develop, and what factors role of fostering regulatory T cell function and influences their decision to become one type terminating pathogenic T cells. of immune cell or another to mediate long term immune protection. Research Projects • “Analysis of effector and regulatory T cells Understanding how the body deals with E [email protected] in type 1 diabetes” using various genetic, E [email protected] pathogens will give clues about how to enhance P 07 3443 8026 immunological or cell based assays P 07 3443 6946 protective immunity. Our goal is to discover new therapies that boost our immune system to researchers.uq.edu.au/ researchers.uq.edu.au/ protect against infection. researcher/25382 researcher/2335 Research Projects • Identifying novel functions of innate lymphoid cells and NK cells in immune protection • Unravelling the microbome-epithelial-immune interface protecting mucosal surfaces • Elucidating the mechanisms responsible for the generation of protective immunity in response to lung and gastrointestinal pathogens Associate Professor Antje Blumenthal Dr Andrew Brooks
Research Field Research Field Innate immunity and infectious diseases Class I cytokine receptor signalling and HLA-G regulation of inflammation Research Synopsis With resistance to antibiotics on the rise, new Research Synopsis insights into host defence mechanisms that Our research focuses on understanding the control pathogenic bacteria are vital for the mechanisms of cytokine receptor signalling development of novel therapeutic interventions. and how these receptors regulate cell behavior Our research focuses on molecular pathways and functions such as inflammation, blood that are important for the recognition and cell formation, postnatal growth, obesity, and control of bacterial pathogens as well as those lactation. Dysregulated cytokine receptor that orchestrate inflammatory responses during signalling leads to many diseases such as cancer infection. and inflammatory diseases such as liver fibrosis, inflammatory bowel disease, and arthritis. The Students are part of a dynamic research team to development of novel molecules that target maximise their research training and experience. cytokine receptors or their signalling pathways The research employs a series of molecular, cell E [email protected] E [email protected] may lead to important therapeutics for a wide biological and immunological techniques to P 07 3443 6984 P 07 3443 7071 variety of clinically important diseases. define novel molecular and cellular aspects of the researchers.uq.edu.au/ researchers.uq.edu.au/ host response to infection. Research Projects researcher/2366 researcher/1699 Research Projects • Understanding dysregulated cytokine receptor signalling in leukaemia • Innate immune recognition of pathogenic bacteria • Defining the mechanisms of cytokine receptor signalling • Molecular regulation of host anti-microbial defence mechanisms • Developing novel therapeutic peptides targeting cytokine receptors • Defining the mechanism of HLA-G inhibition of NK cell activation Dr Janin Chandra Professor Paul Clarke
Research Field Research Field Immunobiology of antigen-presenting cells in Cell cycle control in cancer health and disease Research Synopsis Research Synopsis Paul Clarke is working on the role of cell division Immunotherapy aims to correct a mal- in the development of cancer and in the response functioning immune system to combat a variety of cancer cells to cancer therapies. His research of diseases including cancer, autoimmunity or group investigates the role of tumour suppressors allergies. Many immunotherapy targets have and oncogenes that control mitosis and mitotic been identified and some have been developed cell death. His group study the function of into powerful treatments. Immunotherapy largely proteins in tumour cells using biochemical targets effector T cell responses which are either techniques to identify their post-translational suppressed or falsely activated. Professional modifications (phosphorylation, ubiquitylation) antigen-presenting cells such as dendritic cells and advanced microscopy to analyse their (DCs) play a pivotal role in T cell fates and localisation and stability in live cells. The group are hence a desired immunotherapy target. aim to understand why tumour cells often have E [email protected] E [email protected] Immunotherapy has the potential to effectively abnormal numbers of chromosomes and why P 07 3443 6976 P 07 3443 7990 harness DCs to prime e.g cancer-specific they become resistant to cell death. This work cytotoxic T cell responses or shut-down self- or researchers.uq.edu.au/ will improve our understanding of how cancer researchers.uq.edu.au/ allergen-reactive T cells. My research focusses researcher/2717 develops and will provide new strategies for researcher/17454 on understanding dendritic cell diversity and cancer therapy. fate, and how manipulation of dendritic cells can Research Projects improve disease outcomes. • The role of tumour suppressors in mitosis Research Projects • Control of mitotic cell death • Characterising the diversity of dendritic cells in steady state and disease • The relationship between cellular ageing and cancer • Defining and optimising the mechanisms of action of therapeutic vaccine candidates Professor Riccardo Dolcetti Professor David Evans
Research Field Research Field New strategies to improve cancer Genetics of complex traits and diseases; immunotherapy and immunomonitoring statistical genetics and genetic epidemiology Research Synopsis Research Synopsis Cancer immunotherapy harnesses and enhances Our group aims to elucidate the genetic and the power of the immune system to fight cancer environmental basis of complex traits and and represents the most promising new cancer diseases using statistical approaches that are treatment approach. Indeed, immunotherapy applied to “big data”. constitutes an effective treatment for patients We work on a diverse range of diseases and with certain types of cancer that have been phenotypes including (but not limited to) resistant to chemotherapy and radiation osteoporosis, autoimmune disease, perinatal treatment (e.g. melanoma). Nevertheless, phenotypes like birthweight, and systemic sepsis the clinical benefit provided by current (infection). immunotherapeutic approaches is still limited to 25-30% of treated cancer patients. By exploiting E [email protected] Our research involves many of the world’s E [email protected] the most advanced technologies (nanoparticle- P 07 3443 6953 largest datasets (some >500,000 individuals) P 07 3443 7051 based vaccines, neo-antigens identification and a variety of different technologies including and validation, etc.) and suitable preclinical researchers.uq.edu.au/ RNA-Seq, genome-wide association (GWAS) researchers.uq.edu.au/ models, we are developing innovative strategies researcher/13637 SNP arrays, epigenome-wide methylation arrays, researcher/870 potentially able to improve current approaches. meta-genomic community profiling, and NMR We are also investigating a range of different metabolomics. combinations of immunotherapeutic approaches and conventional treatment modalities to identify We are also very active in the development of the most effective and tailored therapeutic new statistical models to answer interesting schedule. Our final goal is to provide effective questions about biology. We regularly publish in personalised treatments for cancer patients with top tier journals like Nature and Nature Genetics reduced non-specific side-effects. and are proud of our perfect record of 1st class honours students. Research Projects We are searching for high quality students that • Cancer vaccines exploiting the in vivo delivery are highly numerate ideally with a background of tumour specific (neo-)antigens to cross- in genetics, statistics, epidemiology, psychology presenting dendritic cells to improve the and/or computer science. immunotherapy for melanoma, breast cancer, lymphoma, glioblastoma and virus-driven Research Projects tumours • Using genetics to unravel the relationship • Development and validation of clinically between low birthweight and future risk of applicable protocols able to identify tumour- cardio-metabolic disease in later life specific immunogenic neo-epitopes to • Investigating the genetic and genomic basis of be exploited in personalised vaccination septic shock approaches • The genetic basis of osteoporosis • Identification and exploitation of new modalities to induce immunogenic cell death for immunotherapeutic purposes Professor Ian Frazer Dr Fernando S. F. Guimaraes
Research Field Research Field Tumour immunology NK cell biology and immunotherapy Research Synopsis Research Synopsis As immunologists, we work on the skin immune Natural killer (NK) cells can recognise and system and how the immune responses at respond to tumour cells through a broad range squamous epithelial surfaces are influenced by of inhibitory and activating receptors. The epithelial proliferative disease and by the skin regulation of these responses emerges from the microbiome. integrated balance of activating and inhibitory signals at the NK cell-tumour interface, which We work with animal models of human squamous help NK-cells discriminate between altered target skin cancer, and with patients with human cells (cancer or pathogen-infected cells) and squamous skin cancers, as part of a consortium healthy cells. However, both cancer cells and including experts in microbiology, ecogenomics, pathogens can still evade NK cells’ detection and genomics, proteomics and clinical management. killing action. My research focus is to develop effective therapies that maximise NK cell Research Projects E [email protected] E [email protected] responses—an emerging field with great potential P 07 3443 8042 P 07 3443 7049 • Effects of epithelial proliferation on local for applications in the clinical management of immune effector function in skin researchers.uq.edu.au/ disseminated cancer and sepsis prevention. For di.uq.edu.au/profile/3223/ • Bacterial colonisation as a driver of epithelial researcher/228 example, my work has uncovered that members fernando-fonseca-guimaraes proliferation and inflammation of the Transforming Growth Factor (TGF) beta superfamily are potent inhibitory checkpoints • Influence of viral infection on local immune of NK cells function. Their presence within the responses and epithelial proliferation tumour microenvironment and infection sites can lead to tumour immunity and sepsis, respectively. This knowledge is opening a new paradigm for developing cancer and infection immunotherapy approaches. My vision is to build from this discovery and other advances in the field to generate a novel pipeline of cell immunotherapies both “targeting” NK-cells and “based on” NK-cells to increase NK-cells function against cancer (e.g., anti-metastatic function) and sepsis. Research Projects • Developing and tailoring NK cell-based cancer immunotherapies • Deciphering regulatory signalling pathways in NK cells • Elucidating the role of NK cells in inflammatory disorders Professor Nikolas Haass Dr Emma Hamilton-Williams
Research Field Research Field Melanoma cell biology and experimental Immunology and pathogenesis of type 1 diabetes melanoma therapy Research Synopsis Research Synopsis Type 1 diabetes is an autoimmune disease with Using cutting-edge technology, including no cure. Our laboratory focuses on investigating real-time cell cycle and cell death imaging in the immune defects leading the destruction the several three-dimensional cell culture and in vivo insulin producing cells of the pancreas and type models, we investigate the biology of tumour 1 diabetes and studying immunotherapeutic heterogeneity with the goal to develop novel strategies to correct these defects. We also therapeutic approaches by simultaneously study environmental drivers that may trigger the targeting different melanoma subpopulations. autoimmune process, with a focus on the role of the gut microbiota and how the microbiota may Research Projects be manipulated to prevent disease. • Modulating phenotypic melanoma heterogeneity and lymphocyte infiltration to The Hamilton-Williams laboratory currently has improve both targeted and immune therapy E [email protected] two major areas of focus. E [email protected] P 07 3443 7087 P 07 3443 6989 • The role of microtubule-dependent (1) Immunotherapy for type 1 diabetes. We are ‘mechanosensing’ in melanoma plasticity, researchers.uq.edu.au/ investigating the use of a liposome system for researchers.uq.edu.au/ invasion and therapy researcher/2966 antigen-specific immunotherapy in type 1 diabetes. researcher/2724 • Defining molecular signatures that orchestrate Our goal is to restore tolerance in autoreactive tumor subpopulations in melanoma models islet-specific T cells. We are using multi- mimicking tumor microenvironment and drug dimensional profiling of antigen-specific T cells to tolerance optimise our immunotherapy strategy. • Induction of endoplasmic reticulum stress to (2) The role of the microbiota in type 1 diabetes. potentiate immunogenic cell death to improve Using patient stool samples and a novel melanoma therapy proteomic approach we seek to understand how • Generating mathematical models of 4D changes in the gut microbiota function in type 1 multicellular melanoma spheroids (joint project diabetes alter the islet immune response. with Professor Matthew Simpson, QUT) We are using germ-free mice colonised with human derived microbiota to study how changes in the gut flora of patients may modify the immune response and lead to disease. We are also using human cohort and intervention studies with a multi-omic analysis approach to understand how the host and microbiota interact in the lead-up to disease onset. Research Projects • Host-microbiota interactions in the pathogenesis of type 1 diabetes: wet lab and dry lab (bioinformatics based) projects available • Nanoparticle based immune therapies for tolerance induction in type 1 diabetes Professor Kiarash Khosrotehrani Dr Xiaowen Liang
Research Field Research Field Skin regeneration, skin cancer Liver cancer Research Synopsis Research Synopsis The Experimental Dermatology Group has three Liver cancer is the fastest increasing cancer with main streams focused on regenerative medicine the 4th highest cancer mortality rate worldwide. and cancer in Dermatology and skin biology. Despite significant advances in the treatment of liver cancer, response rates of current treatments Research Projects are still low. Our projects aim to investigate and (1) Keratinocyte cancers are the most frequent understand the role of tumour self-seeding and malignancy in humans. In particular, basal cell tumour microenvironments (hepatic stellate cells) carcinomas affect one in 3 Australian from age in liver cancer progression and chemoresistance. 70. The main morbidity of basal cell carcinoma is The success of these studies will identify a new related to the onset of new tumours in the same cell population within primary tumour with sun-exposed skin field. It is therefore essential to prognostic and therapeutic potential and provide develop new strategies to prevent the onset of new strategies to improve the response to current E [email protected] E [email protected] new basal cell carcinomas. Proposed projects: treatments and prevent the relapse of liver P 07 3443 7088 P 07 3443 7487 cancer. a - Developing a preventive immunotherapy researchers.uq.edu.au/ researchers.uq.edu.au/ against Basal cell carcinoma Research Projects researcher/2078 researcher/13428 b - Epidermal ablation to reduce skin cancer • Therapeutic targeting of tumour self-seeded incidence cells in liver cancer (2) Melanoma is the most lethal form of skin • Investigating the mechanism of chemotherapy- cancer. The development of metastases is reliant induced hepatic stellate cell activation in liver on the activation of vascular stem cells in the cancer tumour and in the site of future metastases. Proposed projects: a - To develop biomarkers for the identifications of patients at risk of melanoma progression and metastases. b - To develop inhibitors of vascular stem cells to prevent melanoma metastasis. (3) Skin wound vascularisation is an essential step of the healing process to supply oxygen and nutrient to the surrounding cells. Upon wound closure, most endothelial cells from blood vessels undergo a mesenchymal transition and contribute to scarring. In this project we aim to evaluate the impact of IL6 signalling on vascular stem cells’ transition towards a mesenchymal and pro-fibrotic fate. In all projects there are ample opportunities for strong clinical linkage and PhD or MD PhD. Dr Aideen McInerney-Leo Dr Ahmed Mehdi
Research Field Research Field Translating genomics into clinical practice Genomic medicine, Computational Immunology, Research Synopsis Bioinformatics and COVID-19 biomarkers I am a clinician-academic whose interactions Research Synopsis with patients have shaped my research questions The novel coronavirus disease-2019 (COVID-19) and fuelled my enthusiasm for the importance is a recently emerged human pathogenic of clinical research. I trained as a genetic disease and announced as a pandemic by the counsellor and my research now focuses on the WHO. A number of genomic, proteomics and integration of genomics into clinical care. My cellular markers have been uncovered that research program has had three primary themes: correlate with disease onset. The COVID-19 evaluating the psychosocial impact of genetic symptoms can vary from modest, mild to severe conditions and/or genetic testing; evaluating respiratory distress syndrome. The factors that genetics education preferences for patients and trigger COVID-19 patients to get severe disease healthcare providers; and using next-generation are largely unknown, but are believed to be a sequencing to increase diagnostic yield for rare combination of prior health conditions and some E [email protected] E [email protected] disorders. immune system dysregulation. Our vision is that P 07 3443 7957 P 04 8868 6072 Research Projects a better understanding of COVID-19 progression di.uq.edu.au/profile/2913/ mechanisms can be established by integrating researchers.uq.edu.au/ • Exploring whether genetic fatalism affects aideen-mcinerney-leo the huge resource of the heterogeneous data researcher/8047 sun-related health behaviours in high-risk that is currently being generated in COVID-19 individuals following genetic testing research. • Evaluating the efficacy of videos to promote informed consent for genetic testing In this research project the student(s) will learn the process of performing Biostatistics and • Mainstreaming Genetic Testing for Melanoma Bioinformatics approaches towards predictive into Dermatology Practice.X COVID-19 markers. A search strategy has been already established for the identification of studies of interest. They will use and learn R programming language, linear and/or probabilistic modelling. Research Projects • Prediction models of severe onset of COVID-19 • Developing connectivity maps of COVID-19 disease Professor Mark Morrison Dr Fiona Simpson
Research Field Research Field Microbial biology and metagenomics Cancer immunotherapy Research Synopsis Research Synopsis The microbiome is a new frontier in biomedical The laboratory is developing adjuvant / research. It is the fusion of the traditional fields combination therapy to improve efficacy of medical microbiology (pathogenesis and of treatment for monoclonal antibody epidemiology) with environmental microbiology therapy and to decrease innate and acquired and ecology (the study of microbial diversity and resistance. Consequently the laboratory also function in their natural environment). has cell biological projects on immune cell trafficking, proteins involved in biogenesis of We are investigating and defining the roles of the the immunological synapse and monitoring of microbiome in unique clinical studies of Asian and immune responses during therapy and tumour Australian cohorts to advance a pathophysiology- regression. based classification of gastrointestinal diseases, such as Crohn’s disease. Research Projects E [email protected] • Combination therapies to improve monoclonal E [email protected] To do this, we use innovations in microbial P 07 3443 6957 P 0422 721 656 genomics and metagenomics to better antibody therapy outcomes characterise the metabolic and bioactive researchers.uq.edu.au/ • Cell biological mechanisms of biogenesis of the researchers.uq.edu.au/ landscape of the gut microbiome during health researcher/4157 immune synapse researcher/896 and disease; and how diet modulates the ecological drivers of the microbiome. Our overarching objective is to better treat and prevent these diseases by thwarting the underlying mechanisms, rather than controlling symptoms. Research Projects • Not all methane is created equally: the role of methanogens and the consequences of a diet- induced inflammatory microbiota • Epithelial metabolism as a mediator of host- microbiome interactions in inflammatory bowel disease • The Eastern IBD Gut Microbiota (ENIGMA) project – a comparative study of diet x microbiome interactions in the East and West as drivers of Crohn’s disease incidence • The bioactive landscape of the skin microbiota Dr Chris Slape Professor H. Peter Soyer
Research Field Research Field Leukaemia; pre-leukaemia, stem cells Early detection of melanoma Research Synopsis Research Synopsis Pre-leukaemia is any abnormal haematopoietic Professor Soyer is an internationally renowned state which precedes leukaemia. In some cases academic dermatologist with over 30 (eg. myelodysplastic syndrome), it is clinically years experience in the field with special apparent. In other cases (eg. T cell leukaemia), expertise in preventative dermatooncology, patients do not present until acute leukaemia is dermatopathology and dermatologic imaging. apparent, and the pre-leukaemic phase can be His main research focus is skin cancer (both considered a missed opportunity for therapy. melanoma and keratinocyte skin cancer), with a particular interest in early detection strategies One of the features of many pre-leukaemic and expanding the concept and applications of states is, paradoxically, a deficiency of cell teledermatology and teledermoscopy. He is Chief numbers in certain stem cell and progenitor cell Investigator of the CRE for the Study of Naevi populations. In our models, we have found that was awarded an NHMRC Partnership Grant to restoration of these cell numbers, by various E [email protected] E [email protected] implement an innovative 3D teledermatology manipulations, mitigates or abolishes progression P 07 3443 7074 P 07 3443 8017 network for the early detection of melanoma in to full leukaemia. Our current aims are centred researchers.uq.edu.au/ high risk individuals. He was awarded a MRFF researchers.uq.edu.au/ on understanding the mechanisms by which researcher/14297 Practitioner Fellowship, Next Generation Clinical researcher/1918 this occurs, and identifying ways to exploit this Researchers Program. Most recently he obtained finding for therapeutic implementation. funding from the Australian Cancer Research We use in vivo and in vitro models, multi-colour Foundation (ACRF) to establish the Australian flow cytometry, single cell RNA sequencing Centre of Excellence in Melanoma Imaging & and imaging technologies to drive our research. Diagnosis (ACEMID). ACRF ACEMID will enable All projects have flexible scope and can establishment of 15 3D total body imaging accommodate the diverse interests of students. systems, linked by a telemedicine network, across Australia’s east coast, and facilitate research in Research Projects the early detection of melanoma. • T cell pre-leukaemia detection in humans Research Projects • Eph-ephrin interactions in pre-leukaemia • CRE for the Study of Naevi • Cell competition as a tumour suppressor • NHMRC Partnership Grant (APP1153046) to mechanism implement an innovative 3D teledermatology • Therapeutic progenitor restoration in pre- network for the early detection of melanoma in leukemic mice high risk individuals • Imaging analysis of deficient and restored • Australian Cancer Research Foundation (ACRF) progenitor populations Australian Centre of Excellence in Melanoma Imaging and Diagnosis (ACEMID) Dr Mitchell Stark Associate Professor Ray Steptoe
Research Field Research Field Melanoma/skin cancer genomics and biomarker Understanding the mechanisms and discovery requirements of peripheral T-cell tolerance Research Synopsis Research Synopsis My research group is based within the Peripheral T-cell tolerance crucially limits the Dermatology Research Centre at UQDI and our development of immune-mediated diseases such overall theme is to identifying biomarkers for the as type 1 diabetes and allergies. early detection of melanoma and skin cancers. By The research performed is directed at preventing melanoma/skin cancer formation in its determining how the immune system controls earliest stages, we can effectively put the brakes T-cell responses and studies focus on the role on and halt the formation of metastatic disease. antigen-presenting cells play in this process At the other end of the spectrum, late-stage and how this might be exploited for therapeutic melanoma patients are currently being treated benefit. with effective therapies but unfortunately this doesn’t apply to everybody. By investigating the E [email protected] Experimental studies employ a range of E [email protected] clinical utility of predictive and prognostic ‘liquid P 07 3443 8027 genetically-modified transgenic and gene- P 07 3443 6959 biopsy’ biomarkers, we aim to improve the overall deficient mice to explore what the requirements efficacy of current therapies. researchers.uq.edu.au/ for T-cell are and the molecular mechanisms that researchers.uq.edu.au/ researcher/12961 contribute. researcher/1361 Together with our biomarker discovery, we are also currently creating a “pre-cancer” atlas of Research Projects over-lapping genomic data (exome, RNA-seq, • Gene expression profiling in peripheral methylation) from skin and naevi to identify novel tolerance induction mechanisms for melanoma development which may provide avenues for potential therapeutic • Turning-off T-cell responses that underlie intervention. autoimmune diabetes Research Projects • Therapy of allergic airway inflammation using • Melanoma and Naevi genomics and gene therapy transcriptomics • Does B-cell lymphoma evade immune attack • MicroRNA analysis of the progression of early by inducing T-cell tolerance? skin lesions toward SCC • Predictive and prognostic biomarkers for melanoma brain metastasis • Functional validation of molecular pathways involved in Seborrhoeic Keratosis development Professor Michael Stowasser Associate Professor Rick Sturm
Research Field Research Field Pathogenesis (including genetics), diagnosis and Human pigmentation genetics, naevi and management of hypertension, with an emphasis melanoma on secondary endocrine forms Research Synopsis Research Synopsis The overall goal of my research group is to The Endocrine Hypertension Research combine population genetic studies of human Centre conducts research into all forms of pigmentation with basic discoveries in the human hypertension, with particular expertise molecular and cellular biology of melanocyte cells in endocrine varieties, especially primary that are responsible for skin, hair and eye colour. aldosteronism (PA), renovascular hypertension, We are also conducting a study of germline pheochromocytoma and the syndrome and somatic mutations in genes associated with of familial hypertension and hyperkalemia total body mole count, and in skin biopsies and (Gordon’s syndrome, named after the Centre’s cultured naevus cells. founder). Its demonstration 20 years ago that PA is ten times more common than previously E [email protected] This information will be used to understand E [email protected] thought led to the identification of thousands P 07 3176 2694 individual risk of developing melanoma and P 07 3443 7380 of patients in whom hypertension has been to design a clinical management program for cured or markedly improved following surgical researchers.uq.edu.au/ preventative screening of melanoma. researchers.uq.edu.au/ or specific medical treatment. The centre has researcher/20 researcher/96 made major contributions to improving diagnosis This will allow a personalised assessment of and management of PA, from screening to risk incorporating individual genotype and confirmatory testing (recently designing and phenotypic host risk factors together with regular validating the highly reliable yet streamlined total body screening of dermoscopic patterns of seated saline suppression test) to differentiating naevi. surgically curable unilateral adrenal forms Research Projects from bilateral forms (treated medically). It also • Genetics of human pigmentation traits including described a new familial variety, and helped comparing individuals of high and low mole elucidate its genetic basis (Nature Genetics, 2018). number, and looking at genes controlling mole A recently formed international collaboration with morphology, melanogenesis, tanning, freckling five other research groups in Europe and USA is and iris pigmentation exploring how dietary potassium regulates blood pressure. • Cell biology of human pigmentation through characterisation of primary cultures of Research Projects human melanocytes alone or together with • Improving methods to detect and diagnose keratinocytes to assay function of genes and primary aldosteronism (PA) and its subtypes examine the UV induced tanning response • Exploring genotype/phenotype correlations in • Whole exome sequence and bioinformatic patients with aldosterone-producing adenomas analysis of patients at high risk of melanoma and cell culture of melanocytic lesions • Identifying genetic mutations responsible for PA • Exploring renal molecular pathways by which potassium regulates blood pressure • The role of the mineralocorticoid receptor in regulating brown fat and metabolic status Professor Ranjeny Thomas Professor John Upham
Research Field Research Field Antigen-specific immunotherapy of autoimmune Immune dysregulation in asthma and host disease defence against respiratory viruses Research Synopsis Research Synopsis We have developed nanoparticle-based Our program of translational research is focussed immunotherapy for antigen-specific prevention on the study of immune function and dysfunction and treatment of autoimmune disease. in asthma, and host defence against respiratory viruses, especially human rhinoviruses. To understand the T cell response to autoantigens in autoimmune diseases of skin, We are interested in the mechanisms leading thyroid, salivary glands, joints and pancreatic to excessive airway inflammation in asthma, islets we are isolating and characterising the T and why people with asthma are unusually cell receptors of antigen-specific cells and T cell susceptible to asthma attacks during respiratory clones. viral infections.
We are then developing tests to identify those E [email protected] Our aim is to discover new therapeutic targets in E [email protected] cells in patient blood, so that suitable individuals P 07 3443 6960 severe asthma. P 07 3443 7000 can be identified and cells can be monitored after Research Projects treatment. researchers.uq.edu.au/ researchers.uq.edu.au/ researcher/396 • The function of antigen presenting cells, innate researcher/6780 Research Projects lymphoid cells and NK cells • TCR analysis of autoreactive T cells • The role of polarising cytokines such as IL-33, IL-25 and TSLP in altering host defence against viruses • How macrolide antibiotics alter immune function • How dietary fibre and the gut microbiome alter immune function in chronic lung disease Professor Brandon Wainwright Dr Haolu Wang
Research Field Research Field Developing new therapies for paediatric brain Mesenchymal stem cells, liver diseases, cancer liver cancer Research Synopsis Research Synopsis Brain cancer is the most common cause Mesenchymal stem cells (MSCs) show homing of cancer-related death in children. Since in injured, inflamed or ischemic liver as well as the establishment of core radiotherapy and liver cancer, together with adhesion to the liver chemotherapy approaches around 25 years ago sinusoidal endothelium (engraftment) medicated overall survival has not improved at all despite through CD29 and CD44. Until now, MSCs have many clinical trials. Additionally, for those children been used as a therapy for liver diseases in 55 who survive they commonly suffer serious long clinical trials (searching results from clinicaltrial. term side effects of the treatment itself. Therefore gov). The extent of cell engraftment and function there is an urgent need for better treatments to has been shown to be related to the dosing route improve survival, and to discover approaches to and number of hepatocyte affected. both prevent and treat the side effects of therapy. E [email protected] We are generating functional normal liver E [email protected] The Wainwright laboratory discovered the first P 07 3443 7093 cells and liver cancer cells using in vitro 3D cell P 07 3443 7488 gene known to cause brain cancer in children. culture platform, and studying the interaction researchers.uq.edu.au/ researchers.uq.edu.au/ Since that time we have focused on defining and crosstalk between cancer cells, MSCs, researcher/115 researcher/20211 the cells of origin of the disease, the genetic MSC-derived liver cells, and liver cells. We pathways that lead to tumour growth and are also investigating the in vivo functional metastasis and the development and testing integration of human MSC-derived liver cells of new therapies. Our approaches include cell into mouse livers and assessing if these cells can biology, developmental neurobiology, genetics/ be used as therapeutics against liver diseases. genomics/bioinformatics and, increasingly, In complementary studies, we are studying the immunotherapies. We have strong and seeding and migrating process of cancer cells in active clinical linkages locally, nationally and the liver. internationally and a number of projects that are Research Projects either in the clinic, or will be in the next 12 months. • Generation of functional liver cells from Research Projects mesenchymal stem cells for cell therapy • Manipulating the inflammatory response to • Disarming the cancer cells form seeding and reduce the side effects of chemotherapy and migrating to the liver radiotherapy • The discovery of genes which influence the response of medulloblastoma to radiotherapy • Factors which regulate the blood-brain barrier and therapeutic effectiveness in brain cancer • Attacking cell cycle regulation and the cytoskeleton in medulloblastoma – the molecular basis of the response and drug resistance • A liquid biopsy approach to monitoring molecular basis of therapeutic response and relapse in brain tumour patients Dr Nicole Warrington Dr James Wells
Research Field Research Field Genetics of early life growth; Statistical genetics Tumour immunology Research Synopsis Research Synopsis The development of obesity often occurs in Our group has 2 major areas of focus. early life and tends to persist into adulthood. (1) Immune system recognition and destruction of Unfavourable growth in early life is associated squamous skin cancers. with adverse cardio-metabolic outcomes in later life, such as type two diabetes and heart disease. We are investigating the mechanisms through Understanding the mechanisms underlying this which immune cells destroy tumours. Our relationship is a vital step in combating these goal is to determine how immune cells destroy lifestyle diseases and evaluating the likely success tumours using animal models, so that we can of early interventions. Our research investigates correlate this information to patients in order to the genetic basis of early life growth and uses highlight appropriate points and strategies for genetic information to understand the links immunotherapy. between early life growth and cardio-metabolic E [email protected] E [email protected] health in adulthood. (2) Tumor behavior that permits squamous skin P 07 3443 7347 cancers to evade host immunity. P 07 3443 6983 Research Projects researchers.uq.edu.au/ Using genetically-linked regressor and progressor researchers.uq.edu.au/ • What maternal characteristics modify the researcher/8867 tumours, we are seeking to understand how a researcher/2515 early life environment and cause rapid early life tumour modifies the immune system in order to weight growth in her offspring? become established. Our goal is to understand • Is there a time period in early life where rapid the key early immunological events that allow weight growth causes increased risk of cardio- tumours to evade the immune system. metabolic disease in later life, independent of Research Projects adult obesity? • Assessing mechanisms of immune-control for their role in mediating tumor regression • Defining how tumours harness the immune system in order to establish themselves Dr Timothy Wells Professor Di Yu
Research Field Research Field Host-pathogen interactions in chronic lung T-cell Immunology and Immunotherapy disease Research Synopsis Research Synopsis Dr Di Yu is a leading immunologist with a major Our laboratory focuses on the interactions research focus on the function of T cell subsets between bacterial pathogens and the host in autoimmune diseases, infection and cancer. immune response during chronic lung infections His research utilises mouse models to dissect such as bronchiectasis and cystic fibrosis. immune mechanisms, analytic approaches to monitor individuals’ immune features and Although antibody usually protects against clincial trials to modulate immune respsonses. infection, our laboratory has identified a specific He published in top-tier journals including type of ‘inhibitory antibody’ that actually protects Nature, Nature Immunology, Nature Medicine colonising bacteria from immune killing. and Immunity and is a Clarivate Highly Cited Patients with this ‘inhibitory antibody’ were found Researcher (2019). to have worse lung function. E [email protected] Research Projects E [email protected] We aim to understand both the bacterial causes P 07 3443 6956 • The regulation of T cell-B cell interaction in P 07 3443 6954 and the induction of the immunological response researchers.uq.edu.au/ vaccination and autoimmune diseases researchers.uq.edu.au/ that leads to inhibition of bacterial killing. researcher/15250 • Protective and pathogenic function of cytotoxic researcher/25123 We also have a keen interest in studying T cells in infection and cancer inhibitory antibodies in the context of the whole lung microbiome in patients by using a mixture • Cytokine-based immunotherapy of molecular microbiology, immunology and • Using machine learning to understand the genomic approaches. human immune system Research Projects • The impact of inhibitory antibodies on the human microbiota • Antibody-mediated inhibition of phagocytosis • Antibody-mediated enhancement of inflammation For more information, please contact
T: +61 7 3443 7018
W: di.uq.edu.au/study
A: The University of Queensland Diamantina Institute Level 7, Translational Research Institute 37 Kent Street, Woolloongabba Q Australia 4102
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