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The role of tissue-resident memory T cells in barrier immunity, cancer and autoimmune diseases
Infections are commonly acquired through barrier tissues such as the skin, gut and lung, hence establishing memory CD8+ killer T cell populations at these sites is critical for effective immune protection. Likewise, an effective local memory CD8+ T cell response is critical to cancer immunosurveillance, preventing the development and spread of solid tumours. While most memory T cells circulate in the blood, a distinct lineage, termed tissue-resident memory T (TRM) cells, resides and remains in peripheral tissues. Our group has shown that these cells form a defensive barrier providing immediate local control of viral infection and cancer recurrence. Our current research focuses on developing novel strategies to boost TRM cell responses, and therefore exploit these cells in settings such as vaccination and cancer immunotherapy. Work in our laboratory also aims to understand the role of TRM cells in autoimmune conditions such as psoriasis and alopecia areata and investigate new approaches to eliminate pathological cells from peripheral tissues.
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Understanding the fate decisions that govern memory T cell development
An effective immunological memory response is required for protection against disease throughout an individual’s lifetime. Following exposure to antigen, naïve T cells expand and differentiate to resolve an infection, after which memory T cells are formed to provide long-lasting protective immunity. The memory T cell pool can be partitioned into heterogeneous populations, each possessing different migratory and functional properties, and whose development relies on genetic regulators and environmental signals. Understanding these cell fate decisions provides an avenue to enhance immunological memory responses. Using various infection and tumour models, our group is investigating the regulatory cues and mechanisms that govern memory T cell development in different tissues, with a focus on the transcriptional networks that regulate commitment to various memory T cell lineages.
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Identifying the mechanisms of immune cell development in peripheral tissues
It is now clear that various immune cell populations including T cells, innate lymphoid cells and NKT cells can establish tissue residency and persist long-term in peripheral tissues. Our group is interested in the role of the tissue microenvironment in shaping these immune cell populations and are studying the tissue-tropic factors and microbial signals that govern the environmental adaptation of immune cells to different tissues. We are also investigating the effect of commensalism and microbial experience on immune cell populations and tissue homeostasis. Our goal is to decipher the molecular framework for tissue-resident lymphocyte differentiation, which will provide a basis for targeting these cells in future immune cell-based therapies.
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Whole body analysis of human T cell development and function
The majority of T cell responses occur in tissues; however, current knowledge of human T cells is largely derived from blood. In collaboration with the Australian Donation and Transplantation BioBank (ADTB), our group studies the T cell landscape in multiple lymphoid, visceral and barrier sites from research-consented organ donors. We seek to investigate immune cell distribution across the body and understand the pathways that guide T cell differentiation and maintenance in diverse tissue sites. Our work aims to better-inform the development of immunotherapies that modulate tissue-based cellular responses.
Professor Laura Mackay
+61 3 8344 8016 | lkmackay@unimelb.edu.au
- Position:
- Laboratory Head, Theme Leader in Immunology
- Theme(s):
- Immunology
- Discipline(s):
- Discovery Research
- Unit(s):
- The University of Melbourne, Department of Microbiology and Immunology (DMI)
- Lab Group(s):
- Laura Mackay Group
Professor Laura Mackay is a Laboratory Head and Immunology Theme Leader at The Doherty Institute. Laura is a Howard Hughes Medical Institute (HHMI) and Bill & Melinda Gates International Scholar, a Dame Kate Campbell Fellow, a Sylvia & Charles Viertel Charitable Foundation Senior Medical Research Fellow, a National Health and Medical Research Council (NHMRC) Leadership Fellow, and in 2022 was the youngest ever Fellow elected to the Australian Academy of Health and Medical Sciences. Laura obtained her PhD from The University of Birmingham, U.K. in 2009, before commencing a post-doctoral position with Professor Francis Carbone at The University of Melbourne. In 2016, she established her laboratory at The Doherty Institute.
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Key Achievements
Publications
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Laura has been at the forefront of research into tissue-resident memory T cells, resulting in publications in journals including Science, Nature, Nature Immunology, Nature Medicine, Science Immunology, Cancer Cell and PNAS. Laura has been listed as a Highly Cited Researcher (Clarivate) annually since 2019. Her work has been recognised by multiple awards including the AAMRI Rising Star Award (2023), Jian Zhou Medal (2023), LEO Foundation Award (Asia-Pacific) (2023), The Prime Minister’s Prize for Frank Fenner Life Scientist of the Year (2019), the Australian Academy of Science Gottschalk Medal (2019), Eureka Prize for Outstanding Early Career Researcher (2019), The Woodward Medal in Science and Technology (2019), The Michelson Prize for Human Immunology (2018), and the Victorian Young Tall Poppy Award (2016). She serves on Editorial Boards including Cell, Science Immunology, and Trends in Immunology, and Strategic Advisory Boards including the Lymphoid Dynamics and HIV Persistence Program in South Africa, and the Singapore Immunology and Inflammation Cluster. Laura is also co-host on National Triple R Radio science show, Einstein-A-Go-Go and co-organiser of Global Immunotalks. Her research is supported by the National Health and Medical Research Council (NHMRC), Australian Research Council (ARC), Howard Hughes Medical Institute (HHMI), Bill & Melinda Gates Foundation, Sylvia & Charles Viertel Charitable Foundation, The Michelson Foundation and commercial partnerships.
ProjectsLoading ORCID data…Research Groups-
Laura Mackay Group
The Mackay Lab studies memory T cell responses, with a focus on the signals that control tissue-resident memory T cell differentiation, and a view to harness these cells to develop new treatments against infection, cancer and autoimmune conditions.
Lab Team
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Laboratory Head, Theme Leader in Immunology
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Senior Research Officer
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Dr Ali ZaidSenior Research Officer
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Dr Thomas BurnResearch Officer
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ARC DECRA Research Fellow
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Dr Raissa FonsecaARC DECRA Research Fellow
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Senior Research Fellow
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Dr Josh (Hyun Jae) LeeResearch Officer
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Dr Kelly PatonResearch Officer
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Dr Tobias PochDFG Walter Benjamin Programme Fellow
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Dr Natasha ZamudioLaboratory Manager
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Dr Pirooz ZareieARC DECRA Research Fellow
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Honorary Research Fellow
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Keely McDonaldResearch Assistant
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Allison ClatchPhD Candidate
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James DosserPhD Candidate
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Rachel EvansPhD Candidate
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Louis Hua-Yi LeePhD Candidate
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Andreas ObersPhD Candidate
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Maleika OsmanPhD Candidate
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Justine SeowPhD Candidate
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Hongjin LaiPhD Candidate (Visiting Scholar)
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Joey KuaiMasters Student
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Chloe LowHonours Student
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