Professor Massimo Hilliard
NHMRC Leadership Fellow - GL
Queensland Brain Institute
Affiliate of Clem Jones Centre for Ageing and Dementia Research
Clem Jones Centre for Ageing Dementia Research
+61 7 334 66390
Professor Massimo Hilliard: Molecular and cellular neurobiology
The Hilliard laboratory is focused on understanding the molecular mechanisms that regulate neuronal development, maintenance and repair, using C. elegans as a model system. The group’s current research goals are: (1) how the axon, which is the longest of the neuronal processes, is subdivided into structurally and functionally different compartments, (2) how the axon maintains its structure and function over the lifetime of the organism, and (3) how the axon can be repaired when severing damage occurs.
Researcher biography
Queensland Brain Institute
Dr Massimo A. Hilliard received his PhD in Biological Chemistry and Molecular Biology in 2001 from the University of Naples, Italy. His experimental work, performed at the Institute of Genetics and Biophysics of the CNR (Italian National Council of Research), was aimed at understanding the neuronal and genetic basis of aversive taste behavior (bitter taste) in C. elegans.
During his first postdoc at the University of California, San Diego, using the Ca2+ indicator Cameleon he published the first direct visualisation of chemosensory activity in C. elegans neurons. In his second postdoctoral work at the University of California, San Francisco and at The Rockefeller University, he switched from neuronal function to neuronal development, focusing in particular on how neurons establish and orient their polarity with respect to extracellular cues.
From September 2007, he is at the Queensland Brain Institute where he established an independent laboratory.
Journal Articles
Martínez-Mármol, Ramón, Giordano-Santini, Rosina, Kaulich, Eva, Cho, Ann-Na, Przybyla, Magdalena, Riyadh, Md Asrafuzzaman, Robinson, Emilija, Chew, Keng Yih, Amor, Rumelo, Meunier, Frédéric A., Balistreri, Giuseppe, Short, Kirsty R., Ke, Yazi D., Ittner, Lars M. and Hilliard, Massimo A. (2023). SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity. Science Advances, 9 (23) eadg2248, 1-15. doi: 10.1126/sciadv.adg2248
Vijayaraghavan, Tarika, Dhananjay, Samiksha, Ho, Xue Yan, Giordano-Santini, Rosina, Hilliard, Massimo and Neumann, Brent (2023). The dynamin GTPase mediates regenerative axonal fusion in Caenorhabditis elegans by regulating fusogen levels. PNAS Nexus, 2 (5) pgad114, pgad114. doi: 10.1093/pnasnexus/pgad114
Ding, Qiao, Kesavan, Kaamini, Lee, Kah Meng, Wimberger, Elyse, Robertson, Thomas, Gill, Melinder, Power, Dominique, Chang, Jeryn, Fard, Atefeh T., Mar, Jessica C., Henderson, Robert D., Heggie, Susan, McCombe, Pamela A., Jeffree, Rosalind L., Colditz, Michael J., Hilliard, Massimo A., Ng, Dominic C. H., Steyn, Frederik J., Phillips, William D., Wolvetang, Ernst J., Ngo, Shyuan T. and Noakes, Peter G. (2022). Impaired signaling for neuromuscular synaptic maintenance is a feature of Motor Neuron Disease. Acta Neuropathologica Communications, 10 (1) 61, 61. doi: 10.1186/s40478-022-01360-5
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
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
Ding, Qiao, Chaplin, Justin, Morris, Matthew J., Hilliard, Massimo A., Wolvetang, Ernst, Ng, Dominic C. H. and Noakes, Peter G. (2021). TDP-43 mutation affects stress granule dynamics in differentiated NSC-34 motoneuron-like cells. Frontiers in Cell and Developmental Biology, 9 611601, 611601. doi: 10.3389/fcell.2021.611601
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
Giordano-Santini, Rosina, Kaulich, Eva, Galbraith, Kate M., Ritchie, Fiona K., Wang, Wei, Li, Zhaoyu and Hilliard, Massimo A. (2020). Fusogen-mediated neuron−neuron fusion disrupts neural circuit connectivity and alters animal behavior. Proceedings of the National Academy of Sciences, 117 (37), 201919063-23065. doi: 10.1073/pnas.1919063117
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
Neumann, Brent and Hilliard, Massimo A. (2019). Axonal repair by fusion: pitfalls, consequences and solutions. FASEB Journal, 33 (12), 13071-13074. doi: 10.1096/fj.201901407R
Linton, Casey, Riyadh, M. Asrafuzzaman, Ho, Xue Yan, Neumann, Brent, Giordano-Santini, Rosina and Hilliard, Massimo A. (2019). Disruption of RAB-5 increases EFF-1 fusogen availability at the cell surface and promotes the regenerative axonal fusion capacity of the neuron. Journal of Neuroscience, 39 (15), 2823-2836. doi: 10.1523/jneurosci.1952-18.2019
Neumann, Brent, Linton, Casey, Giordano-Santini, Rosina and Hilliard, Massimo A. (2019). Axonal fusion: an alternative and efficient mechanism of nerve repair. Progress in Neurobiology, 173, 88-101. doi: 10.1016/j.pneurobio.2018.11.004
Donato, Alessandra, Kagias, Konstantinos, Zhang, Yun and Hilliard, Massimo A. (2019). Neuronal sub-compartmentalization: a strategy to optimize neuronal function. Biological Reviews. doi: 10.1111/brv.12487
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
Chand, Kirat K., Lee, Kah Meng, Lee, John D., Qiu, Hao, Willis, Emily F., Lavidis, Nickolas A., Hilliard, Massimo A. and Noakes, Peter G. (2018). Defects in synaptic transmission at the neuromuscular junction precedes motor deficits in a TDP-43Q331K transgenic mouse model of amyotrophic lateral sclerosis. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 32 (5), fj201700835R-2689. doi: 10.1096/fj.201700835R
Ritchie, Fiona K., Knable, Rhianna, Chaplin, Justin, Gursanscky, Rhiannon, Gallegos, Maria, Neumann, Brent and Hilliard, Massimo A. (2017). The heterochronic gene lin-14 controls axonal degeneration in C. elegans neurons. Cell Reports, 20 (12), 2955-2965. doi: 10.1016/j.celrep.2017.08.083
Gokce, Sertan Kutal, Hegarty, Evan Marley, Mondal, Sudip, Zhao, Peisen, Ghorashian, Navid, Hilliard, Massimo A. and Ben-Yakar, Adela (2017). A multi-trap microfluidic chip enabling longitudinal studies of nerve regeneration in Caenorhabditis elegans. Scientific Reports, 7 (9837) 9837, 9837. doi: 10.1038/s41598-017-10302-4
Abay, Zehra C, Wong, Michelle Yu-Ying, Teoh, Jean-Sébastien, Vijayaraghavan, Tarika, Hilliard, Massimo A and Neumann, Brent (2017). Phosphatidylserine save-me signals drive functional recovery of severed axons in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 114 (47), 1-10. doi: 10.1073/pnas.1703807114
Fogarty, Matthew J., Klenowski, Paul M., Lee, John D., Drieberg-Thompson, Joy R., Bartlett, Selena E., Ngo, Shyuan T., Hilliard, Massimo A., Bellingham, Mark C. and Noakes, Peter G. (2016). Cortical synaptic and dendritic spine abnormalities in a presymptomatic TDP-43 model of amyotrophic lateral sclerosis. Scientific Reports, 6 (1) 37968, 37968. doi: 10.1038/srep37968
Giordano-Santini, Rosina, Linton, Casey and Hilliard, Massimo A. (2016). Cell-cell fusion in the nervous system: alternative mechanisms of development, injury and repair. Seminars in Cell and Developmental Biology, 60, 146-154. doi: 10.1016/j.semcdb.2016.06.019
Gallotta, Ivan, Mazzarella, Nadia, Donato, Alessandra, Esposito, Alessandro, Chaplin, Justin C., Castro, Silvana, Zampi, Giuseppina, Battaglia, Giorgio S., Hilliard, Massimo A., Bazzicalupo, Paolo and Di Schiavi, Elia (2016). Neuron-specific knock-down of SMN1 causes neuron degeneration and death through an apoptotic mechanism. Human Molecular Genetics, 25 (12), 2564-2577. doi: 10.1093/hmg/ddw119
Nichols, Annika L.A., Meelkop, Ellen, Linton, Casey, Giordano-Santini, Rosina, Sullivan, Robert K., Donato, Alessandra, Nolan, Cara, Hall, David H., Xue, Ding, Neumann, Brent and Hilliard, Massimo A. (2016). The apoptotic engulfment machinery regulates axonal degeneration in C. elegans neurons. Cell Reports, 14 (7), 1673-1683. doi: 10.1016/j.celrep.2016.01.050
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
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
Neumann, Brent and Hilliard, Massimo A. (2014). Loss of MEC-17 leads to microtubule instability and axonal degeneration. Cell Reports, 6 (1), 93-103. doi: 10.1016/j.celrep.2013.12.004
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
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
Schlipalius, David I., Valmas, Nicholas, Tuck, Andrew G., Jagadeesan, Rajeswaran, Ma, Li, Kaur, Ramandeep, Goldinger, Anita, Anderson, Cameron, Kuang, Jujiao, Zuryn, Steven, Mau, Yosep S., Cheng, Qiang, Collins, Patrick J., Nayak, Manoj K., Schirra, Horst Joachim, Hilliard, Massimo A. and Ebert, Paul R. (2012). A core metabolic enzyme mediates resistance to phosphine gas. Science, 338 (6108), 807-810. doi: 10.1126/science.1224951
Cáceres, Ivan de Carlos, Valmas, Nicholas, Hilliard, Massimo A. and Lu, Hang (2012). Laterally orienting C. elegans using geometry at microscale for high-throughput visual screens in neurodegeneration and neuronal development studies. PLoS One, 7 (4) e35037, e35037.1-e35037.8. doi: 10.1371/journal.pone.0035037
Kirszenblat, Leonie, Pattabiraman, Divya and Hilliard, Massimo A. (2011). LIN-44/Wnt directs dendrite outgrowth through LIN-17/Frizzled in C. elegans neurons. PLoS Biology, 9 (9) e1001157, 0nline. doi: 10.1371/journal.pbio.1001157
Neumann, Brent, Nguyen, Ken C. Q., Hall, David H., Ben-Yakar, Adela and Hilliard, Massimo A. (2011). Axonal regeneration proceeds through specific axonal fusion in transected C. elegans neurons. Developmental Dynamics, 240 (6), 1365-1372. doi: 10.1002/dvdy.22606
Burne, T. H. J., Scott, E., van Swinderen, B., Hilliard, M., Reinhard, J., Claudianos, C., Eyles, D. W. and McGrath, J. J. (2011). Big ideas for small brains: What can psychiatry learn from worms, flies, bees and fish?. Molecular Psychiatry, 16 (1), 7-16. doi: 10.1038/mp.2010.35
Hilliard, Massimo (2009). Axonal degeneration and regeneration: a mechanistic tug-of-war. Journal Of Neurochemistry, 108 (1), 23-32. doi: 10.1111/j.1471-4159.2008.05754.x
Guo, Samuel X., Bourgeois, Frederic, Chokshi, Trushal, Durr, Nicholas J., Hilliard, Massimo A., Chronis, Nikos and Ben-Yakar, Adela (2008). Femtosecond laser nanoaxotomy lab-on-a-chip for in vivo nerve regeneration studies. Nature Methods, 5 (6), 531-533. doi: 10.1038/nmeth.1203
Chalasani, Sreekanth H., Feinberg, Evan H. and Hilliard, Massimo A. (2007). Global 'worming'. Genome Biology, 8 (9) 314, 314-1-314-3. doi: 10.1186/gb-2007-8-9-314
Pan, Chun-Liang, Howell, James Endres, Clark, Scott G., Hilliard, Massimo, Cordes, Shaun, Bargmann, Cornelia I. and Garriga, Gian (2006). Multiple Wnts and frizzled receptors regulate anteriorly directed cell and growth cone migrations in Caenorhabditis elegans. Developmental cell, 10 (3), 367-377. doi: 10.1016/j.devcel.2006.02.010
Hilliard, Massimo A. and Bargmann, Cornelia I. (2006). Wnt signals and Frizzled activity orient anterior-posterior axon outgrowth in C. elegans. Developmental Cell, 10 (3), 379-390. doi: 10.1016/j.devcel.2006.01.013
Sapio, Maria Rosaria, Hilliard, Massimo A., Cermola, Michele, Favre, Reneé and Bazzicalupo, Paolo (2005). The Zona Pellucida domain containing proteins, CUT-1, CUT-3 and CUT-5, play essential roles in the development of the larval alae in Caenorhabditis elegans. Developmental Biology, 282 (1), 231-245. doi: 10.1016/j.ydbio.2005.03.011
Hilliard, Massimo A., Apicella, Alfonso J., Kerr, Rex, Suzuki, Hiroshi, Bazzicalupo, Paolo and Schafer, William R. (2005). In vivo imaging of C. elegans ASH neurons: Cellular response and adaptation to chemical repellents. The EMBO Journal 24, 1489-1489, 24 (1), 63-72. doi: 10.1038/sj.emboj.7600493
Hilliard, Massimo A., Bergamasco, Carmela, Arbucci, Salvatore, Plasterk, Ronald H. A. and Bazzicalupo, Paolo (2004). Worms taste bitter: ASH neurons, QUI-1, GPA-3 and ODR-3 mediate quinine avoidance in Caenorhabditis elegans. The EMBO Journal, 23 (5), 1101-1111. doi: 10.1038/sj.emboj.7600107
Rugarli, Elena I., Di Schiavi, Elia, Hilliard, Massimo A., Arbucci, Salvatore, Ghezzi, Cristina, Facciolli, Anna, Coppola, Giuseppe, Ballabio, Andrea and Bazzicalupo, Paolo (2002). The Kallmann syndrome gene homolog in C. elegans is involved in epidermal morphogenesis and neurite branching. Development, 129 (5), 1283-1294.
Hilliard, Massimo A., Bargmann, Cornelia I. and Bazzicalupo, Paolo (2002). C. elegans responds to chemical repellents by integrating sensory inputs from the head and the tail. Current Biology, 12 (9), 730-734. doi: 10.1016/S0960-9822(02)00813-8
Rinaldo, Cinzia, Bazzicalupo, Paolo, Ederle, Sara, Hilliard, Massimo and La Volpe, Adriana (2002). Roles for Caenorhabditis elegans rad-51 in meiosis and in resistance to ionizing radiation during development. Genetics, 160 (2), 471-479.
Salcini, Anna Elisabetta, Hilliard, Massimo Antonio, Croce, Assunta, Arbucci, Salvatore, Luzzi, Paola, Tacchetti, Carlo, Daniell, Laurie, De Camilli, Pietro, Pelicci, Pier Giuseppe, Di Fiore, Pier Paolo and Bazzicalupo, Paolo (2001). The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling. Nature Cell Biology, 3 (8), 755-760. doi: 10.1038/35087075
Bazzicalupo, P., Hilliard, M., Lewis, E., De Riso, L., Sebastiano, M. and Ristoratore, F. (1994). Neurons and genes involved in chemical sensitivity in nematodes. Parasite, 1 (1), 58-60. doi: 10.1051/parasite/199401s1058
Conference Papers
Scott, Hamish S., Matotek, Ebony, Mattiske, Tessa, Bryson-Richardson, Robert J., Smyth, Ian, Gecz, Jozef, Christodoulou, John, Palpant, Nathan, Smith, Kelly, Warr, Coral, Bennetts, Bruce, Thomas, Paul, Bowles, Josephine, Hilliard, Massimo, Hime, Gary, Hool, Livia, Quinn, Leonie, Wolvetang, Ernst, Jamieson, Robyn, Baynam, Gareth, Dudding-Byth, Tracy, Tan, Tiong Yang, Milnes, Di, Wallis, Mathew, Palmer, Elizabeth, Patel, Chirag, Jones, Kristi, Tam, Patrick, Stark, Zornitza ... Sinclair, Andrew (2024). How the Australian Functional Genomics Network (AFGN) contributes to improved patient care. Pathology Update 2024, Adelaide, SA, Australia, 1-3 March 2024. Oxford, United Kingdom: Elsevier. doi: 10.1016/j.pathol.2023.12.084
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.
Kim, Shin Ae, Lee, Hyewon, Hilliard, Massimo and Lu, Hang (2014). High-throughput multichannel array device for selective stimulation and long-term in vivo imaging in C. elegans. Food, Pharmaceutical and Bioengineering Division 2014 - Core Programming Area at the 2014 AIChE Annual Meeting, Atlanta GA, United States, 16-21 November 2014. American Institute of Chemical Engineers.
Lee, Hyewon, Kim, Shin Ae, Aubry, Guillaume, Mugno, Paula, Hilliard, Massimo and Lu, Hang (2012). Fast target-selective chemical & optical stimulation based on high-throughput multi-channel imaging device. 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2012, Okinawa, Japan, 28 October - 1 November 2012. San Diego, CA, United States: Chemical and Biological Microsystems Society.
Guo, Samuel X., Bourgeois, Frederic, Chokshi, Trushal, Durr, Nicholas J., Hilliard, Massimo, Chronis, Nikos and Ben-Yakar, Adela (2008). Femtosecond laser nanosurgery in microfluidic devices and its emerging role in nerve regeneration studies. doi: 10.1109/LEOS.2008.4688576