Vascular biology and development

Discovering the unexpected through forward genetic screens

The distribution of blood cells, hormones and essential nutrients throughout our bodies is dependent on the function of a healthy circulatory system.

The formation of the fascinating network of vessels that permeate our major organs is of fundamental interest in biology. The vasculature is also centrally important in cardiovascular diseases and in cancer progression.

The Hogan Group aims to better understand how the vasculature forms during development and to translate their findings into a deeper understanding of disease.The Hogan Group studies several aspects of vascular development and biology.

Research overview

“Broadly, we investigate vertebrate vascular system development using high-throughput genetic approaches for gene discovery and live-imaging to visualise developmental processes at cellular and individual protein resolutions,” said Group Leader, Associate Professor, Ben Hogan.

The Group’s focus is on lymphatic vessel development and perivascular lineages of the neurovasculature.

“We use forward genetic screens in the zebrafish as our primary tool to discover new genes and molecular mechanisms that are essential for the formation of different vascular lineages. This approach allows the unbiased discovery of genes and mechanisms and allows us to discover the unexpected.”

The Hogan Group also use transgenic approaches in zebrafish and live 4D imaging to study different vascular lineages, report gene expression changes and study the consequences of morphogenesis and specific signalling events in developing cells.

Research projects

Gene Discovery: What are the genetic networks, signalling proteins and transcription factors that control the development of our vasculature?
We have recently completed a screen for zebrafish mutants that fail to form lymphatic vessels but form relatively normal blood vasculature. In this IMB screen, we identified more than 30 mutants and simultaneously mapped them using our integrated whole genome sequencing and bioinformatics pipeline. This has led to the discovery of more than 12 new molecular regulators of lymphatic vessel formation, new models of disease and unexpected molecular mechanisms of development. Current work is dissecting new mechanisms and gene functions arising from our mutant analyses in-depth in zebrafish and mice.

In Vivo Cell Biology: How do physical forces during morphogenesis control vascular development and endothelial cell signalling?
We have begun to generate imaging-based biosensors that report changes in the mechanical state of different proteins and are working towards sensors that report active signalling in vivo during development. In the future, we hope to understand how changes in forces that act during morphogenesis influences key signalling events, downstream cell identity decisions and modify gene expression in development and disease models.

Vegfc/Vegfr3 Signalling and Disease Models
We use mutants, genome editing and transgenesis to generate new models for the study of Vegfc/Vegfr3 signalling in developing vessels. These studies utilise zebrafish and mouse embryo models and aim to identify and understand new targets in this central pathway in lymphangiogenesis and angiogenesis. In addition, current work includes using innovative new models of pathological lymphangiogenesis to screen for small molecule inhibitors acting in this pathway.

To discuss the group's projects further, contact Associate Professor Ben Hogan

+61 7 3346 2105
b.hogan@imb.uq.edu.au

Research training opportunities

Research title: Vascular biology and development

Summary of research interests: My group studies the development of the embryonic vasculature with a focus on the discovery of novel genes involved in blood and lymphatic vessel development in the embryo. We are particularly interested in the development of lymphatic vessels, as the lymphatic vasculature plays critical roles in several human diseases and is a validated target for the inhibition of cancer metastasis. We study the processes of cell fate specification, precursor cell migration and the differentiation of vascular endothelial cells using the zebrafish embryo as a model system. The approaches we use include molecular genetics (mutant identification and characterisation, as well as the analysis of key genes of interest) and high-resolution in vivo imaging of the cellular processes driving the development of the vasculature in the embryo. Ultimately, we aim to elucidate molecular and cellular mechanisms that control vessel development and to understand how the pathways and processes we identify contribute to human disease.

Traineeships, honours and PhD projects include

  • Analysis of key signalling pathways in lymphatic vascular development in zebrafish
  • Molecular and cellular characterisation of zebrafish mutants with defective vascular development
  • Genome editing with CRISPR and TALENs to characterise mechanisms of vascular development and disease.

Contact: Associate Professor Ben Hogan

+61 7 3346 2105
b.hogan@imb.uq.edu.au


Find out more about Research Training at IMB:

Research Training

Featured publications

  • Overman, Jeroen, Fontaine, Frank, Moustaqil, Mehdi, Mittal, Deepak, Sierecki, Emma, Sacilotto, Natalia, Zuegg, Johannes, Robertson, Avril A. B., Holmes, Kelly, Salim, Angela A., Mamidyala, Sreeman, Butler, Mark S., Robinson, Ashley S., Lesieur, Emmanuelle, Johnston, Wayne, Alexandrov, Kirill, Black, Brian L., Hogan, Benjamin M., De Val, Sarah, Capon, Robert J., Carroll, Jason S., Bailey, Timothy L., Koopman, Peter, Jauch, Ralf, Smyth, Mark J., Cooper, Matthew A., Gambin, Yann and Francois, Mathias (2017) Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice. eLife, 6 . doi:10.7554/eLife.21221

  • De Angelis, Jessica E., Lagendijk, Anne K., Chen, Huijun, Tromp, Alisha, Bower, Neil I., Tunny, Kathryn A., Brooks, Andrew J., Bakkers, Jeroen, Francois, Mathias, Yap, Alpha S., Simons, Cas, Wicking, Carol, Hogan, Benjamin M. and Smith, Kelly A. (2017) Tmem2 regulates embryonic Vegf signaling by controlling hyaluronic acid turnover. Developmental Cell, 40 2: 123-136. doi:10.1016/j.devcel.2016.12.017

  • Bower, Neil I., Vogrin, Adam J., Le Guen, Ludovic, Chen, Huijun, Stacker, Steven A., Achen, Marc G. and Hogan, Benjamin M. (2017) Vegfd modulates both angiogenesis and lymphangiogenesis during zebrafish embryonic development. Development, 144 3: 507-518. doi:10.1242/dev.146969

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Engagement and impact

A/Prof Hogan is currently the Co-Head of the Division of Genomics of Development and Disease at the Institute for Molecular Bioscience and Co-Director of the University of Queensland's Centre for Cardiac and Vascualr Biology. He has published in numerous leading journals that include Nature Genetics, Genes and Development, Cell Reports, Current Biology, Blood, Development, Physiology, Developmental Biology and Human Molecular Genetics. He has written recent invited reviews and commentaries for Nature, Development and Physiology. A/Prof Hogan is currently an NHMRC and National Heart Foundation Co-funded Career Development Fellow and has previously held fellowship funding from the ARC, EMBO, Cancer Council of Victoria and was an NHMRC CJ Martin Fellow.

His research has expanded our knowledge in the formation of lymphatic vasculature and identified new mechanisms of vessel development of relevance in cancer, cardiovascular disease and inherited lymphoedema. A/Prof Hogan's achievements have recently been recognised by the award of the Queensland Heart Foundations Reseracher of the year award (2014) and the Emerging Leader Award of the Australia New Zealand Society for Cell and Developmental Biology (2016). He holds current research funding from the NHMRC, ARC, Cancer Council and Heart Foundation.

Partners and collaborators

  • Marc Achen and Steven Stacker, Peter MacCallum Cancer Centre, Melbourne, AUSTRALIA
  • Markus Affolter and Henry Belting, Basel Biozentrum, Basel, SWITZERLAND
  • Mat Francois, Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA
  • Natasha Harvey, Centre for Cancer Biology, the University of South Australia, Adelaide, AUSTRALIA
  • Naomi Mochizuki, National Cerebral and Cardiovascular Center, Osaka, JAPAN
  • Cas Simons, Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA
  • Kelly Smith, Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA
  • Alpha Yap, Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, AUSTRALIA

     

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A/Prof Ben Hogan

Associate Professor Ben Hogan

Co-Division Head, Genomics of Development and Disease Division
Investigator, Centre for Rare Diseases Research

  +61 7 3346 2105  
  b.hogan@imb.uq.edu.au
  IMB Researcher Profile
  Centre for Cardiac and Vascular Biology


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  Group Leader

  • Associate Professor Ben Hogan

    Division Head & Group Leader, Genomics of Development and Disease Division
    Co-Director
    UQ Centre for Cardiac & Vascular Biology
    Honorary Associate Professor
    Institute for Molecular Bioscience

  Researchers

  • Dr Neil Bower

    Research Fellow
    Institute for Molecular Bioscience
  • Dr Emma Gordon

    IMB Fellow
    Senior Research Fellow-Group Leader
    Institute for Molecular Bioscience
  • Dr Anne Lagendijk

    Senior Research Fellow - GL & Group Leader, Division of Genomics of Development and Disease
    Institute for Molecular Bioscience
  • Dr Kazuhide Okuda

    Research Officer
    Institute for Molecular Bioscience
  • Ms Maria Rondon Galeano

    Research Assistant
    Institute for Molecular Bioscience

  Students