Dr Julian Heng - Researcher Profile

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Address

Faculty of Medicine, Nursing & Health Sciences
Monash University, Clayton

Biography

He’s just one year into his position as group leader at the Australian Regenerative Medicine Institute (ARMI) and researcher Dr Julian Heng is already forging a reputation as one of Australia’s most promising young neuroscientists in the area of brain development. Julian’s primary research – focusing on the production of new nerve cells in the brain – may have huge implications for clinicians in identifying therapies to treat intellectual disability, as well as in the design of future therapies to exploit the limited regenerative capacity within the adult brain in times of injury or stress.

 

A self confessed ‘geekish’ curiosity in transcription factor biology led Dr Julian Heng to investigate how gene products control cell differentiation. Julian believes that these processes underpin current knowledge of how stem cells generate mature cell types, such as nerve cells. By learning about these processes, Julian’s research group will be able to direct how stem cells mature into different cell types within the body.

 “We are beginning to understand how genes and their mutations can affect brain development, and lead to intellectual disability and complex social behavioural disorders. However, it also appears that the control of gene expression is a critically important process that must be correctly executed during normal brain development in order to produce a normal, healthy brain. This process is governed by the functions of transcription factors,” he says.

At present, Julian is working on genes that are known to be associated with human neurological development and disorders that precipitate intellectual disability. Mutations in these genes may lead to abnormal brain development. Too much or too little of a given gene can, for example, result in brain malformation and intellectual disability, or to conditions such as Autism Spectrum Disorder.

“The regulation of how much of a given gene is present in the cells in the developing brain makes a big difference, and we are interested in the role for transcription factors to control gene expression in immature brain cells,” Julian says.

The capacity of the adult human brain for neurogenesis— the processes by which neurons are generated from neural stem and progenitor cells —is a subject relevant to research carried out in the lab. 

 “I believe these studies we do in the laboratory will increase our understanding of neurodevelopment and, at the same time, provide new avenues to exploit the limited regenerative capacity in the brain to be able to make the most crucial kinds of neurons that we need to replace in case of injury and disease.”

Heng’s ARMI research team is trying to find ‘the circuit board’ or the ‘instruction manual’ to make the correct kind of neuron for the brain. There is, he maintains, good evidence in experimental studies that they can achieve this.

The future applications of this emerging area of research are exciting, not only for neuroscience, but for multiple research areas, considering the limited capacity for regeneration in the adult human brain. One of the most immediate applications is transplantation medicine.

“We will definitely be able to use this information in the future to direct stem cells to produce neurons of our choosing to differentiate in a dish. These may well belong to the patient, as you would take bone marrow out of the patient and generate white blood cells from them and put them back in the patient. You might be able to do the same for brain stem cells,” Julian says.

“Rather than to roll the dice and to generate neurons from donor stem cells, but not be very sure about what kinds of neurons they are, you might be able to produce the right kinds of neurons needed to able to transfer to patients that suffer from brain diseases, such as Parkinson’s.”

In addition to bearing therapeutic and clinical outcomes, the research could also lead to screening tests which would provide the sort of information that would allow families to organise early interventions for individuals with intellectual disability in their care.

 

Qualifications

DOCTOR OF PHILOSOPHY
Institution: Melbourne University
Year awarded: 2003
BACHELOR OF SCIENCE (HONOURS, FIRST CLASS)
Institution: University of Western Australia
Year awarded: 1997

Publications

Journal Articles

Alfano, C., Viola, L., Heng, J.I., Pirozzi, M., Clarkson, M., Flore, G., De Maio, A., Schedl, A., Guillemot, F., Studer, M., 2011, COUP-TFI promotes radial migration and proper morphology of callosal projection neurons by repressing Rnd2 expression, Development [P], vol 138, issue 21, The Company of Biologists Ltd, UK, pp. 4685-4697.

Pacary, E., Heng, J., Azzarelli, R., Riou, P., Castro, D., Lebel-Potter, M., Parras, C., Bell, D.M., Ridley, A.J., Parsons, M., Guillemot, F., 2011, Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling, Neuron [P], vol 69, issue 6, Cell Press, USA, pp. 1069-1084.

Heng, J., Chariot, A., Nguyen, L., 2010, Molecular layers underlying cytoskeletal remodelling during cortical development, Trends in Neurosciences [P], vol 33, issue 1, Elsevier Ltd, UK, pp. 38-47.

Merot, Y., Retaux, S., Heng, J.I., 2009, Molecular mechanisms of projection neuron production and maturation in the developing cerebral cortex, Seminars In Cell & Developmental Biology [P], vol 20, issue 6, Academic Press, UK, pp. 726-734.

Heng, J.I., Nguyen, L., Castro, D., Zimmer, C., Wildner, H., Armant, O., Skowronska-Krawczyk, D., Bedogni, F., Matter, J., Hevner, R., Guillemot, F., 2008, Neurogenin 2 controls cortical neuron migration through regulation of Rnd2, Nature [P], vol 455, issue 7209, Nature Publishing Group, UK, pp. 114-118.

Zhao, X., Heng, J.I., Guardavaccaro, D., Jiang, R., Pagano, M., Guillemot, F., Iavarone, A., Lasorella, A., 2008, The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein, Nature Cell Biology [P], vol 10, issue 6, Nature Publishing Group, UK, pp. 643-653.

Heng, J.I., Moonen, G., Nguyen, L., 2007, Neurotransmitters regulate cell migration in the telencephalon, European Journal Of Neuroscience [P], vol 26, issue 3, Wiley-Blackwell Publishing Ltd, UK & Germany, pp. 537-546.

Ge, W., He, F., Kim, K.J., Blanchi, B., Coskun, V., Nguyen, L., Wu, X., Zhao, J., Heng, J.I., Martinowich, K., Tao, J., Wu, H., Castro, D., Sobeih, M.M., Corfas, G., Gleeson, J.G., Greenberg, M.E., Guillemot, F., Sun, Y.E., 2006, Coupling of cell migration with neurogenesis by proneural bHLH factors, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 103, issue 5, National Academy of Sciences, USA, pp. 1319-1324.

Nguyen, L., Besson, A., Heng, J.I., Schuurmans, C., Teboul, L., Parras, C., Philpott, A., Roberts, J.M., Guillemot, F., 2006, p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex, Genes & Development [P], vol 20, issue 11, Cold Spring Harbor Laboratory Press, USA, pp. 1511-1524.

Hand, R., Bortone, D., Mattar, P., Nguyen, L., Heng, J.I., Guerrier, S., Boutt, E., Peters, E., Barnes, A.P., Parras, C., Schuurmans, C., Guillemot, F., Polleux, F., 2005, Phosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex, Neuron [P], vol 48, issue 1, Cell Press, USA, pp. 45-62.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Genetic analysis of neocortical development in mice..
Supervisors:
Heng, J (Main), Bourne, J (Associate).