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Associate Professor Michael Piper

Professor

School of Biomedical Sciences
Faculty of Medicine

Prof & Director (Research Training)

Research Strategy and Support (Medicine)
Faculty of Medicine

Affiliate Associate Professor

Queensland Brain Institute
m.piper@uq.edu.au
+61 7 334 69873

Overview

I graduated from The University of Tasmania, and received my PhD in Developmental Biology from The University of Queensland in 2003. My PhD, performed at the Institute for Molecular Bioscience with Prof. Melissa Little, centred on understanding the cellular and molecular mechanisms underlying embryonic kidney development. My first postdoc was performed with Prof. Christine Holt at The University of Cambridge, UK, where I studied the mechanisms by which axonal growth cones navigate to their targets in the brain, using the frog Xenopus laevis as a model system. In my second postdoctoral position, with Prof. Linda Richards at the Queensland Brain Institute at The University of Queensland, my work focussed on understanding the molecular mechanisms of neural progenitor cell specification in the developing cerebral cortex. In late 2010, I took up a joint position with the Queensland Brain Institute and The School of Biomedical Sciences (SBMS) to continue my research into the mechanisms underlying neural stem cell differentiation. I have held numerous fellowships during my career, including an NHMRC Howard Florey Fellowship, an NHMRC CDF and an ARC Future Fellowship. I currently hold a continuing Teaching and Research position within SBMS, and am currently the Director for Research Training at SBMS.

Research Impacts

The human brain is an incredibly complex organ, consisting of over 100 billion neurons, and even more glial cells. Further adding to this complexity is the fact that there are a wide variety of distinct neuronal subpopulations within the brain, each with different morphological characteristics, neurochemical properties and patterns of connectivity. Amazingly, nearly all of the cells within the brain are derived from a relatively small population of neural stem cells (NSCs) that proliferate, then differentiate, during embryogenesis. Understanding how NSC biology is coordinated, both spatially and temporally, to generate the mature brain remains one of the great challenges in biology. My vision is to reveal the mechanisms that control NSC differentiation within the developing brain, and to apply this knowledge to understand diseases caused by abnormal NSC differentiation, such as autism and hydrocephalus.

I have made a number of significant contributions to understanding how NSC differentiation is coordinated during neural development since starting my own group in late 2010. This work, which was supported by competitive fellowship (NHMRC Career Development Fellowship 2009-2012; ARC Future Fellowship 2013-2017) and grant funding (three NHMRC project grants as CIA; two ARC Discovery Projects as sole CI), has helped to elucidate the fundamental mechanisms underpinning neurogenesis within the neocortex, hippocampus and cerebellum. I have also defined critical molecular controllers of NSC quiescence, a cellular state that ensures the longevity of adult NSCs, as well as describing the behavioural consequences of aberrant adult neurogenesis. Finally, I have provided new insights into how abnormal stem cell biology can contribute to a range of neurodevelopmental disorders, as well as cancers of the brain and skin. The significance of my findings has been recognised by multiple awards for research excellence, from both national (e.g. 2018 Emerging Leader Award, Australian and New Zealand Society for Cell and Developmental Biology; 2010 AW Campbell Award, Australasian Neuroscience Society) and international agencies (2015 Innovator Award, Hydrocephalus Association; 2010 CJ Herrick Award, American Association for Anatomists). I now am in an ideal position to address aspects of two key questions in the field, namely, what are the transcriptomic and epigenomic factors that control the differentiation of NSCs during brain development, and how do deficits in this process contribute to disease?

I have published 99 manuscripts, over 60% of which have been as first or last author. These include manuscripts in leading jourals such as Nature, Nature Neuroscience, Neuron, The Journal of Neuroscience and Cerebral Cortex. I have published 62 mauscripts since 2015, providing evidence for the upward trajectory of my output. For my full publication record, please visit my Orcid site

Qualifications

  • Doctor of Philosophy, The University of Queensland
  • Bachelor of Science (Honours), University of Tasmania

Publications

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Grants

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Supervision

View all Supervision

Available Projects

  • Understanding the drivers of neural stem cell differentiation

    What are the mechanisms that control neural stem cell (NSC) differentiation during embryogenesis, and that enable the generation of the diverse suite of neurons and glia that comprise the brain? This is a key question in developmental neuroscience. My contribution to this field to date has been to reveal central transcriptional regulators that mediate NSC biology within the brain. Using rodent model systems, I demonstrated that transcription factors of the Nuclear Factor One (NFI) family mediate NSC proliferation and differentiation in the embryonic, postnatal and adult nervous system. This work has received international recognition, as evidenced by numerous invited international presentations and high-impact reviews (e.g. Trends in Cell Biology), and forms the framework around which the hypotheses of this program will be addressed.

    I am interested in defining how NSC proliferation and differentiation is regulated at a transcriptional and epigenomic level within the developing nervous system. Using the developing mouse brain as a model system, we are using a suite of molecular and cellular techniques to understand how diverse regions of the nervous system are generated, including the cerebral cortex, the cerebellum, the spinal cord and the hypothalamus. For example, within the cerebral cortex, we are investigating how the NFI family of transcription factors mediate NSC differentiation, and how mutations to the NFI family culminate in macrocephaly, and disorders such as Malan syndrome. Moreover, we are using mice lacking the gene Nsd1(a histone modifying protein) to investigate the development of a human syndrome known as Sotos syndrome, which is also characterised by macrocephaly. In collaboration with Mikael Boden (SCMB), we are also investigating how changes to chromatin landscapes mediate NSC differentiation, and developing bioinformatic tools to enhance the analysis of RNA-seq and ChIP-seq datasets. Collectively, this work will provide fundamental insights into neural development, as well as insights into human neurodevelopmental disorders that arise as a result of abnormal neural stem cell biology in utero.

  • Adult neurogenesis

    The birth of new neurons within the mature cerebral cortex, a process termed neurogenesis, plays a critical role in learning, memory and spatial navigation. We are investigating various aspects of adult neurogenesis in rodent models, such as neural stem cell quiescence . We are also interrogating the consequences of abnormal neurogenesis using behavioural tests for learning and memory.

    We employ a range of transgenic mice to investigate adult neurogenesis, coupled with techniques ranging from immunocytochemistry, behavioural testing, analysis of axonal connectivity and genome-wide sequencing platforms. Given the critical roles that learning and memory play in our everyday lives, and the fact that neurogenesis within the adult brain diminishes with age, this research will provide fundamental insights into how this vital process is co-ordinated at a cellular and molecular level.

  • Identifying how abnormal neural stem cell biology contributes to disease

    The importance of NSC biology to brain development is underscored by disorders associated with abnormal NSC differentiation, including autism, hydrocephalus and macrocephaly. Despite the role of aberrant NSC development to these disorders, our understanding of the cellular and molecular deficits that contribute to disease onset and progression remains limited. Recently, my work has begun to focus on these disorders. Moreover, as the transcriptional landscape of many cancers resembles that of stem cells during development, I am also applying my expertise to understand how abnormal transcriptional activity contributes to cancer progression. This approach has gained significant traction, as evidenced by international awards (2015 Innovator Award, Hydrocephalus Association) and grants (Simons Foundation Autism Research Initiative, 2018-2019; Cancer Council Queensland, 2016-2017) I have received.

View all Available Projects

Publications

Featured Publications

Book Chapter

  • Ependymal cells in development and disease

    Vidovic, Diana, Piper, Michael and Harvey, Tracey J. (2016). Ependymal cells in development and disease. Hydrocephalus: prevalence, risk factors and treatment. (pp. 39-61) edited by Merle Reeves. New York, NY, United States: Nova Science Publishers.

  • Axon guidance

    Piper, Michael J., Keynes, Roger J. and Cook, Geoffrey M. W. (2012). Axon guidance. eLS. (pp. 1-8) London, United Kingdom: John Wiley & Sons. doi: 10.1002/9780470015902.a0000799.pub3

  • Axon pathfinding

    Strochlic, L., Weinl, C., Piper, M. and Holt, C. E. (2010). Axon pathfinding. Evolution of Nervous Systems. (pp. 187-209) Elsevier Inc.. doi: 10.1016/B0-12-370878-8/00118-X

  • Emx and Nfi Genes Regulate Cortical Development and Axon Guidance in the Telencephalon

    Piper, Michael, Dawson, Amber-Lee S., Lindwall, Charlotta, Barry, Guy, Plachez, Céline and Richards, Linda J. (2008). Emx and Nfi Genes Regulate Cortical Development and Axon Guidance in the Telencephalon. Cortical Development: Genes and Genetic Abnormalities. (pp. 230-242) John Wiley and Sons Ltd.. doi: 10.1002/9780470994030.ch16

  • The role of cyclic nucleotides in axon guidance

    Piper, Michael, van Horck, Francis and Holt, Christine (2007). The role of cyclic nucleotides in axon guidance. Axon growth and guidance. (pp. 134-143) edited by Dominique Bagnard. New York, NY, United States: Springer. doi: 10.1007/978-0-387-76715-4_10

Journal Article

Conference Publication

  • The Glial Differentiation Factor Nuclear Factor One B (Nfib) Induces Differentiation and Inhibits Growth of Glioblastoma.

    Stringer, Brett, Day, Bryan, Barry, Guy, Piper, Michael, Jamieson, Paul, Ensbey, Kathleen, Bruce, Zara, Richards, Linda and Boyd, Andrew (2013). The Glial Differentiation Factor Nuclear Factor One B (Nfib) Induces Differentiation and Inhibits Growth of Glioblastoma.. 4th Quadrennial Meeting of the World-Federation-of-Neuro-Oncology (WFNO) held in conjunction with the 18th Annual Meeting of the Society-for-Neuro-Oncology (SNO), San Francisco, United States, Nov 21-24, 2013. Cary, United States: Oxford University Press. doi: 10.1093/neuonc/not174

  • Transcription factor Lhx2 is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus

    Subramanian, Lakshmi, Sarkar, Anindita, Shetty, Ashwin S., Muralidharan, Bhavana, Padmanabhan, Hari, Piper, Michael, Monuki, Edwin S., Bach, Ingolf, Gronostajski, Richard M., Richards, Linda J. and Tole, Shubha (2012). Transcription factor Lhx2 is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus. 19th Biennial Meeting of the International Society for Developmental Neuroscience (ISDN), Mumbai India, 11-14 January 2012. Oxford, United Kingdom: Pergamon. doi: 10.1016/j.ijdevneu.2012.10.058

  • NFIA controls progenitor cell differentiation through repression of the Notch effector Hes1

    Piper, Michael, Barry, Guy, Hawkins, John, Mason, Sharon, Lindwall, Charlotta, Little, Erica, Moldrich, Randal X., Boyle, Glen M., Gronostajski, Richard M., Bailey, Timothy L. and Richards, Linda (2010). NFIA controls progenitor cell differentiation through repression of the Notch effector Hes1.

  • Emx and Nfi genes regulate cortical development and axon guidance in the telencephalon

    Piper, Michael, Dawson, Amber-Lee S., Lindwall, Charlotta, Barry, Guy, Plachez, Celine and Richards, Linda J. (2007). Emx and Nfi genes regulate cortical development and axon guidance in the telencephalon. Novartis Foundation Symposium 288, London, 6–8 February 2007. Chichester, West Sussex, United Kingdom: Wiley. doi: 10.1002/9780470994030.ch16

Other Outputs

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Understanding the drivers of neural stem cell differentiation

    What are the mechanisms that control neural stem cell (NSC) differentiation during embryogenesis, and that enable the generation of the diverse suite of neurons and glia that comprise the brain? This is a key question in developmental neuroscience. My contribution to this field to date has been to reveal central transcriptional regulators that mediate NSC biology within the brain. Using rodent model systems, I demonstrated that transcription factors of the Nuclear Factor One (NFI) family mediate NSC proliferation and differentiation in the embryonic, postnatal and adult nervous system. This work has received international recognition, as evidenced by numerous invited international presentations and high-impact reviews (e.g. Trends in Cell Biology), and forms the framework around which the hypotheses of this program will be addressed.

    I am interested in defining how NSC proliferation and differentiation is regulated at a transcriptional and epigenomic level within the developing nervous system. Using the developing mouse brain as a model system, we are using a suite of molecular and cellular techniques to understand how diverse regions of the nervous system are generated, including the cerebral cortex, the cerebellum, the spinal cord and the hypothalamus. For example, within the cerebral cortex, we are investigating how the NFI family of transcription factors mediate NSC differentiation, and how mutations to the NFI family culminate in macrocephaly, and disorders such as Malan syndrome. Moreover, we are using mice lacking the gene Nsd1(a histone modifying protein) to investigate the development of a human syndrome known as Sotos syndrome, which is also characterised by macrocephaly. In collaboration with Mikael Boden (SCMB), we are also investigating how changes to chromatin landscapes mediate NSC differentiation, and developing bioinformatic tools to enhance the analysis of RNA-seq and ChIP-seq datasets. Collectively, this work will provide fundamental insights into neural development, as well as insights into human neurodevelopmental disorders that arise as a result of abnormal neural stem cell biology in utero.

  • Adult neurogenesis

    The birth of new neurons within the mature cerebral cortex, a process termed neurogenesis, plays a critical role in learning, memory and spatial navigation. We are investigating various aspects of adult neurogenesis in rodent models, such as neural stem cell quiescence . We are also interrogating the consequences of abnormal neurogenesis using behavioural tests for learning and memory.

    We employ a range of transgenic mice to investigate adult neurogenesis, coupled with techniques ranging from immunocytochemistry, behavioural testing, analysis of axonal connectivity and genome-wide sequencing platforms. Given the critical roles that learning and memory play in our everyday lives, and the fact that neurogenesis within the adult brain diminishes with age, this research will provide fundamental insights into how this vital process is co-ordinated at a cellular and molecular level.

  • Identifying how abnormal neural stem cell biology contributes to disease

    The importance of NSC biology to brain development is underscored by disorders associated with abnormal NSC differentiation, including autism, hydrocephalus and macrocephaly. Despite the role of aberrant NSC development to these disorders, our understanding of the cellular and molecular deficits that contribute to disease onset and progression remains limited. Recently, my work has begun to focus on these disorders. Moreover, as the transcriptional landscape of many cancers resembles that of stem cells during development, I am also applying my expertise to understand how abnormal transcriptional activity contributes to cancer progression. This approach has gained significant traction, as evidenced by international awards (2015 Innovator Award, Hydrocephalus Association) and grants (Simons Foundation Autism Research Initiative, 2018-2019; Cancer Council Queensland, 2016-2017) I have received.

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Links

ResearcherID: B-2805-2010

ORCID: 0000-0002-6759-2560

Scopus ID: 35552383100

Personal Profile: Link

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