Senior Research Fellow
Overview
I received my PhD from The University of Queensland in 2014 where I studied axonal regeneration and degeneration in the laboratory of Professor Massimo Hilliard at the Queensland Brain Institute. In 2016 I was awarded an NHMRC-ARC Dementia Research Development Fellowship to pursue postdoctoral research in Professor Hilliard's lab with the aim of discovering novel genes that regulate axonal degeneration in C. elegans. In 2018 I was awarded a UQ Early Career Researcher Grant and a Young Tall Poppy Science Award. In 2019 I was a visiting scholar in the laboratory of Professor Kang Shen in the Department of Biology at Stanford University, where I studied how mechanosensitive channels regulate dendrite branching through Ca2+ signaling during neuronal development. In 2022 I was awarded an NHMRC Ideas Grant and was recruited to the School of Biomedical Sciences at UQ as a Group Leader. My lab focuses on understanding the cellular mechanisms that protect the nervous system from damage.
Research Interests
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Axonal Degeneration
Degeneration of the axon, the longest process of a neuron, is a key early pathological hallmark of Neurodegenerative conditions, including motor neuron disease, glaucoma, and Parkinson’s, Huntington’s and Alzheimer’s diseases. Despite being described more than 100 years ago, we lack a basic understanding of the cellular and molecular mechanisms regulating axonal degeneration. Using the small nematode worm C. elegans, a very powerful genetic model system, we aim to discover molecules with a protective effect on the axon. The results from this study will provide novel and important insights into how axonal degeneration occurs, and how it can be prevented or delayed, potentially leading to the identification of novel molecular targets to treat neurodegenerative disorders.
Research Impacts
My laboratory focuses on how to build and maintain a nervous system for life. We use C. elegans as a model system because we can use sophisticated genetic, imaging and molecular approaches to study the cellular mechanisms of neuroprotection in exquisite detail.
Failure to maintain the integrity of the axon, the longest and most susceptible compartment of a neuron, results in compromised neuronal function, which is characteristic of both injury and neurodegenerative diseases. Virtually every neuron, including those of the central nervous system, is susceptible to different types of strain insults such as protein accumulation, vascular accidents, and trauma, with excessive mechanical strain triggering axonal degeneration and progression of neurodegenerative diseases. The molecular mechanisms that maintain axonal integrity are unknown and will be essential to develop neuroprotective therapies for human disorders and injury.
Qualifications
- Doctoral Diploma of Neurological Sciences, The University of Queensland
Publications
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Journal Article: Dendrites use mechanosensitive channels to proofread ligand-mediated neurite extension during morphogenesis
Tao, Li, Coakley, Sean, Shi, Rebecca and Shen, Kang (2022). Dendrites use mechanosensitive channels to proofread ligand-mediated neurite extension during morphogenesis. Developmental Cell, 57 (13), 1615-1629.e3. doi: 10.1016/j.devcel.2022.05.019
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Journal Article: EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway
Neumann, Brent, Coakley, Sean, Giordano-Santini, Rosina, Linton, Casey, Lee, Eui Seung, Nakagawa, Akihisa, Xue, Ding and Hilliard, Massimo A. (2015). EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway. Nature, 517 (7533), 219-222. doi: 10.1038/nature14102
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Journal Article: Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen with the use of KillerRed
Williams, Daniel C., El Bejjani, Rachid, Mugno Ramirez, Paula, Coakley, Sean, Kim, Shin Ae, Lee, Hyewon, Wen, Quan, Samuel, Aravi, Lu, Hang, Hilliard, Massimo A. and Hammarlund, Marc (2013). Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen with the use of KillerRed. Cell Reports, 5 (2), 553-563. doi: 10.1016/j.celrep.2013.09.023
Grants
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A new model of ß-Spectrin function: understanding how the skin protects neurons from damage
(2022–2025) NHMRC IDEAS Grants
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Discovering the molecular mechanisms that protect sensory neurons from mechanical damage
(2018) UQ Early Career Researcher
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(2016–2021) NHMRC-ARC Dementia Research Development Fellowships Scheme
Supervision
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Cellular mechanisms of neuroprotection
Doctor Philosophy
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The epidermis shields axons from movement-induced damage
(2022) Doctor Philosophy
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Axonal degeneration and regeneration in C. elegans neurons
Doctor Philosophy
Publications
Featured Publications
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EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway
Neumann, Brent, Coakley, Sean, Giordano-Santini, Rosina, Linton, Casey, Lee, Eui Seung, Nakagawa, Akihisa, Xue, Ding and Hilliard, Massimo A. (2015). EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway. Nature, 517 (7533), 219-222. doi: 10.1038/nature14102
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Williams, Daniel C., El Bejjani, Rachid, Mugno Ramirez, Paula, Coakley, Sean, Kim, Shin Ae, Lee, Hyewon, Wen, Quan, Samuel, Aravi, Lu, Hang, Hilliard, Massimo A. and Hammarlund, Marc (2013). Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen with the use of KillerRed. Cell Reports, 5 (2), 553-563. doi: 10.1016/j.celrep.2013.09.023
Journal Article
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Tao, Li, Coakley, Sean, Shi, Rebecca and Shen, Kang (2022). Dendrites use mechanosensitive channels to proofread ligand-mediated neurite extension during morphogenesis. Developmental Cell, 57 (13), 1615-1629.e3. doi: 10.1016/j.devcel.2022.05.019
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The metalloprotease ADM-4/ADAM17 promotes axonal repair
Ho, Xue Yan, Coakley, Sean, Amor, Rumelo, Anggono, Victor and Hilliard, Massimo A. (2022). The metalloprotease ADM-4/ADAM17 promotes axonal repair. Science Advances, 8 (11) eabm2882, eabm2882. doi: 10.1126/sciadv.abm2882
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Neuron-epidermal attachment protects hyper-fragile axons from mechanical strain
Bonacossa-Pereira, Igor, Coakley, Sean and Hilliard, Massimo A. (2022). Neuron-epidermal attachment protects hyper-fragile axons from mechanical strain. Cell Reports, 38 (10) 110501, 110501. doi: 10.1016/j.celrep.2022.110501
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Gormal, Rachel S., Padmanabhan, Pranesh, Kasula, Ravikiran, Bademosi, Adekunle T., Coakley, Sean, Giacomotto, Jean, Blum, Ailisa, Joensuu, Merja, Wallis, Tristan P., Lo, Harriet P., Budnar, Srikanth, Rae, James, Ferguson, Charles, Bastiani, Michele, Thomas, Walter G., Pardon, Els, Steyaert, Jan, Yap, Alpha S., Goodhill, Geoffrey J., Hilliard, Massimo A., Parton, Robert G. and Meunier, Frédéric A. (2020). Modular transient nanoclustering of activated β2-adrenergic receptors revealed by single-molecule tracking of conformation-specific nanobodies. Proceedings of the National Academy of Sciences of the United States of America, 117 (48), 30476-30487. doi: 10.1073/pnas.2007443117
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Coakley, Sean, Ritchie, Fiona K., Galbraith, Kate M. and Hilliard, Massimo A. (2020). Epidermal control of axonal attachment via β-spectrin and the GTPase-activating protein TBC-10 prevents axonal degeneration. Nature Communications, 11 (1) 133, 1-12. doi: 10.1038/s41467-019-13795-x
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Offenburger, Sarah-Lena, Ho, Xue Yan, Tachie-Menson, Theresa, Coakley, Sean, Hilliard, Massimo A. and Gartner, Anton (2018). 6-OHDA-induced dopaminergic neurodegeneration in Caenorhabditis elegans is promoted by the engulfment pathway and inhibited by the transthyretin-related protein TTR-33. PLoS Genetics, 14 (1) e1007125, 1-27. doi: 10.1371/journal.pgen.1007125
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EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway
Neumann, Brent, Coakley, Sean, Giordano-Santini, Rosina, Linton, Casey, Lee, Eui Seung, Nakagawa, Akihisa, Xue, Ding and Hilliard, Massimo A. (2015). EFF-1-mediated regenerative axonal fusion requires components of the apoptotic pathway. Nature, 517 (7533), 219-222. doi: 10.1038/nature14102
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Lee, Hyewon, Kim, Shin Ae, Coakley, Sean, Mugno, Paula, Hammarlund, Marc, Hilliard, Massimo A. and Lu, Hang (2014). A multi-channel device for high-density target-selective stimulation and long-term monitoring of cells and subcellular features in C. elegans. Lab on a Chip - Miniaturisation for Chemistry and Biology, 14 (23), 4513-4522. doi: 10.1039/c4lc00789a
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Williams, Daniel C., El Bejjani, Rachid, Mugno Ramirez, Paula, Coakley, Sean, Kim, Shin Ae, Lee, Hyewon, Wen, Quan, Samuel, Aravi, Lu, Hang, Hilliard, Massimo A. and Hammarlund, Marc (2013). Rapid and permanent neuronal inactivation in vivo via subcellular generation of reactive oxygen with the use of KillerRed. Cell Reports, 5 (2), 553-563. doi: 10.1016/j.celrep.2013.09.023
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Kirszenblat, Leonie, Neumann, Brent, Coakley, Sean and Massimo Hilliard (2013). A dominant mutation in mec-7/β-tubulin affects axon development and regeneration in Caenorhabditis elegans neurons. Molecular Biology of the Cell, 24 (3), 285-296. doi: 10.1091/mbc.E12-06-0441
Conference Publication
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The metalloprotease ADM-4 promotes regenerative axonal fusion
Ho, X.Y., Coakley, S. and Hilliard, M.A. (2019). The metalloprotease ADM-4 promotes regenerative axonal fusion. International Worm Meeting, UCLA, September. Rockville, MD, United States: Genetics Society of America.
Other Outputs
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The cellular and molecular mechanisms of axonal maintenance and regeneration
Coakley, Sean (2014). The cellular and molecular mechanisms of axonal maintenance and regeneration. PhD Thesis, Queensland Brain Institute, The University of Queensland. doi: 10.14264/uql.2015.153
Grants (Administered at UQ)
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A new model of ß-Spectrin function: understanding how the skin protects neurons from damage
(2022–2025) NHMRC IDEAS Grants
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Discovering the molecular mechanisms that protect sensory neurons from mechanical damage
(2018) UQ Early Career Researcher
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(2016–2021) NHMRC-ARC Dementia Research Development Fellowships Scheme
PhD and MPhil Supervision
Current Supervision
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Cellular mechanisms of neuroprotection
Doctor Philosophy — Principal Advisor
Other advisors:
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Axonal degeneration and regeneration in C. elegans neurons
Doctor Philosophy — Associate Advisor
Other advisors:
Completed Supervision
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The epidermis shields axons from movement-induced damage
(2022) Doctor Philosophy — Associate Advisor
Other advisors:
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(2020) Doctor Philosophy — Associate Advisor
Other advisors:
