Associate Professor Julian Heng  Dr Julian Heng

 

Laboratory Head, Brain Growth and Disease
E: julian.heng@perkins.uwa.edu.au
T: 6151 0769

Profile
Julian Heng investigates the molecular and cellular mechanisms which control the formation of neural circuits during in the brain, as well as to understand how mutations to genes which affect this process can cause human mental disorders, such as epilepsy and intellectual disability.

Julian Heng attained his Bachelor's degree with First Class Honours at the University of Western Australia, and then earned his Doctorate from the University of Melbourne while working within the Howard Florey Institute (now the Florey Institute of Neuroscience and Mental Health). In 2004, he undertook postdoctoral training at the National Institute for Medical Research (Mill Hill, UK), holding a CJ Martin Fellowship as well as an MRC Career Development Fellowship to extend his period of training. He was then awarded a Career Development Fellowship (2011-2014, NH&MRC, Australia) to foster his independent research programme.

Research overview
Julian and his team focuses on the development of new nerve cells within the mammalian brain. Currently, the Heng lab addresses the following areas of research:

Nerve cell in the brain

Confocal image reconstruction of a nerve cell in the
brain which expresses green fluorescent protein.
© Julian Heng

  1. Do mutations to the gene regulatory protein RP58 cause brain disorders in children?
    Recent improvements in genome sequencing technologies have empowered researchers and clinicians with a means to investigate the genetic basis for neurological disorders that result from copy-number variation (CNV). However, what continues to remain a challenge is to establish the pathogenicity of genomic abnormalities, such as CNVs, and their causative effects on nervous system impairment. In this project, we clarify possible genotype-phenotype relationships in human subjects with brain developmental disorder which are associated with microdeletions to 1q43-44. Our investigation has led to the identification of ZNF238 as a critical gene for brain development. Using a range of molecular and cellular approaches combined with in utero electroporation with mice, the goal of this project is to understand how loss of ZNF238 leads to impairments in the production of cerebral cortical neurons during fetal development. This work leads to an improved understanding of the molecular basis for 1q43-44 CNVs in human health and mental dysfunction.
  2. Harnessing Human Genetics to Discover Novel Molecular Pathways for Neuronal Development
    During fetal development, the growth of the cerebral cortex relies on a step-wise process of neurogenesis, cell migration and circuit formation. Failures in these key developmental steps can result in brain disorder and lead to intellectual disability. The goal of this project is to study the neurobiology of brain development disorders with a genetic origin, as well as to characterise novel players in brain development and disease. Through this research, we will better understand the molecular and cellular functions within the developing brain which guide the development of new neural circuits as they fire and wire appropriately. We will apply this knowledge towards developing tools which improve the genetic diagnosis and clinical management of patients born with brain disorders such as epilepsy, intellectual disability and autism.
  3. Understanding the cellular and molecular basis for neuronal migration during brain development and disease
    Migration is a universal property of all newborn neurons of the developing mammalian nervous system (Heng et al, 2010, TiNS). In this project, we will study the functions for protein-coding genes which regulate the ability for immature neurons of the cerebral cortex to position themselves appropriately within the growing fetal brain. We will apply these findings to understand the genetic basis for neuronal migration disorders in humans.


Research projects

Four colour cell stain
 Multi-photon imaging of mouse fetal brain cells
which express different chemical markers 
painted
with different colours. 
© Julian Heng 

Associate Professor Julian Heng studies the molecular and cellular mechanisms which control fetal brain development, with particular emphasis on the production of new nerve cells and their development as functional circuits.  This research has significant implications for the diagnosis and treatment of brain disorders.  In addition, our discoveries contribute to the development of future therapies which enhance the limited regenerative capacity of the adult brain to repair itself through the formation of appropriate replacement circuits in times of injury or stress.  

The following projects are available within the lab:

  • Do mutations to the gene regulatory protein RP58 cause brain disorders in children?
  • Understanding the molecular basis of neuronal migration during brain development and disease

Selected publications

  1. Haas MA, Ngo L, Li SS, Schleich S, Qu Z, Vanyai HK, Cullen HD, Cardona-Alberich A, Gladwyn-Ng IE, Pagnamenta AT, Taylor JC, Stewart H, Kini U, Duncan KE, Teleman AA, Keays DA, Heng JI. De novo mutations in DENR disrupt neuronal development and link congenital neurological disorders to defective mRNA translation re-initiation. 2016 Cell Reports, In Press [IF=8.35]
  2. Berkowicz SR, Featherby TJ, Qu Z, Giousoh A, Borg NA, Heng JI, Whisstock JC, Bird PI. Brinp1-/- mice exhibit autism-like behaviour, altered memory, hyperactivity, and increased Parvalbumin-positive cortical interneuron density. Molecular Autism. 2016, in press. [IF=5.4] [NCBI PubMed Entry]
  3. Gladwyn-Ng, IE, Huang, L, Ngo L, Li SS, Qu Z, Vanyai HK, Cullen HD, Davis JM, Heng JI. Bacurd1/Kctd13 and Bacurd2/Tnfaip1 are interacting partners to Rnd proteins which influence the long-term positioning and dendritic maturation of cerebral cortical neurons. Neural Development. 2016 Mar 11;11(1):7. doi: 10.1186/s13064-016-0062-1. [IF=3.72] [NCBI PubMed Entry]
  4. Harris L., Zalucki O., Piper M, Heng JI. Insights into the biology and therapeutic applications of neural stem cells. Stem Cells International. 2016, doi:10.1155/2016/9745315. [IF=2.81] [Stem Cells International]
  5. Hemming IA, Forrest AR, Shipman P, Woodward KJ, Walsh P, Ravine DG, Heng JI. Reinforcing the association between distal 1q CNVs and structural brain disorder: A case of a complex 1q43-q44 CNV and a review of the literature. American Journal of Medical Genetics Part B Neuropsychiatric Genetics. 2016 Feb 7. doi: 10.1002/ajmg.b.32427. [IF=2.3] [NCBI PubMed Entry]
  6. Sim J, Scerri T, Fanjul Fernandez M, Risely J, Gillies G, Pope K, van Roozendaal H, Heng JI, Mandelstam S, McGillivray G, McGregor D, Kannan L, Maixner W, Harvey SA, Amor D, Delatycki M, Crino P, Bahlo M, Lockhart P, Leventer R. Familial cortical dysplasia caused by mutation in the mTOR regulator NPRL3. Annals of Neurology. 2015 accepted [IF= 9.97] [NCBI PubMed Entry]
  7. Xu X-J, Jaehne EJ, Greenberg Z, McCarthy P, Saleh E, Parish CL, Heng JI, Haas M, Baune BT, Ratnayke U, Buuse M, Lopez AF, Ramshaw HS, Schwarz Q. Deficiency of 14-3-3ζ causes behavioural and anatomical defects associated with neurodevelopmental disorders. Scientific Reports. 2015 Jul 24;5:12434. doi: 10.1038/srep12434 [IF=5.078] 
  8. Gladwyn-Ng L, Li SS, Qu Z, Davis JM, Ngo L, Haas MA, Singer JD, Heng JI. Bacurd2 is a novel interacting partner to Rnd2 which controls radial migration within the developing mammalian cerebral cortex. Neural Development. 2015 2015 Mar 31;10:9. doi: 10.1186/s13064-015-0032-z. [IF=3.72] Manuscript is “Highly Accessed”. [NCBI PubMed Entry]
  9. Ngo L, Haas M, Qu Z, Li SS, Zenker J, Teng KS-L, Gunnersen JM, Breuss M, Habgood M, Keays DA, Heng JI. TUBB5 and its disease-associated mutations influence the terminal differentiation and dendritic spine densities of cerebral cortical neurons. Human Molecular Genetics. 2014 May 15. pii: ddu238. [NCBI PubMed Entry]
  10. Heng JI*, Qu Z, Ohtaka-Maruyama C, Okado H, Kasai M, Castro DS, Guillemot F, Tan S-S. The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cortical development. Cerebral Cortex. 2013. doi: 10.1093/cercor/bht277. Epub 2013 Oct 1 (*denotes corresponding author) [NCBI PubMed Entry]
  11. Ohtaka-Maruyama C, Hirai S, Miwa A, Heng JI, Shitara H, Ishii R, Taya C, Kawano H, Kasai M, Nakajima K, Okado H. RP58 Regulates the Multipolar-Bipolar Transition of Newborn Neurons in the Developing Cerebral Cortex. Cell Reports. 2013 Feb 21;3(2):458-71. doi: 10.1016/j.celrep.2013.01.012. Epub 2013 Feb 7. [NCBI PubMed Entry]
  12. Haas M, Qu Z, Kim TH, Vargas E, Campbell K, Petrou S, Tan S-S, Reid CA, Heng JI. Perturbations in cortical development and seizure susceptibility arising from prenatal exposure to benzodiazepines in mice. European Journal of Neuroscience. 2013 May;37(10):1584-93. doi: 10.1111/ejn.12167. [NCBI PubMed Entry]
  13. Heng JI*, Breuss M*, Poirier K, Tian GL, Jaglin JH, Qu Z, Braun A, Gstrein T, Ngo L, Haas M, Bahi-Buisson N, Moutard M-L, Passemard S, Verloes A, Gressens P, Xie YL, Robson KJH, Rani DS, Thangaraj K, Clausen T, Chelly J, Cowan NJ, Keays DA. Mutations in the b-tubulin Gene TUBB5 Cause Microcephaly with Structural Brain Abnormalities. Cell Reports. 2012 Dec 27;2(6):1554-62. (*denotes equal authorship) [NCBI PubMed Entry]
  14. Kim TH, Richards K, Heng JI, Petrou S, Reid CA.  Two lines of transgenic mice expressing cre recombinase exhibit increased seizure susceptibility. Epilepsia. 2012 Nov 26. doi:pii: S0920-1211(12)00311-7. [NCBI PubMed Entry]
  15. Bogoyevitch MA, Yeap YY, Qu Z, Ngoei KR, Yip YY, Zhao TT, Heng JI, Ng DC (2012) WD40-repeat protein 62 is a JNK-phosphorylated spindle pole protein required for spindle maintenance and timely mitotic progression. Journal of Cell Science. 2012 Nov 1;125(Pt 21):5096-109. [NCBI PubMed Entry]
  16. Alfano C, Viola L, Heng JI, 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. Nov;138(21):4685-97. [NCBI PubMed Entry]
  17. Pacary E, Heng JI, Azzarelli R, Riou P, Castro DS, Lebel-Potter M, Parras C, Bell DM, Ridley AJ, Parsons M, Guillemot F (2011) Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signalling.  Neuron, 24;69(6):1069-84. [NCBI PubMed Entry]
  18. Heng JI*, Chariot A, Nguyen L* (2010) Molecular layers underlying cytoskeletal remodelling during cortical development.  Trends in Neurosciences, 33(1):38-47. (*corresponding authors) [NCBI PubMed Entry]
  19. Mérot Y, Rétaux S, Heng JI* (2009) Molecular mechanisms of projection neuron production and maturation in the developing cerebral cortex. Seminars in Cell and Developmental Biology, 20(6):726-34. (*corresponding author) [NCBI PubMed Entry]
  20. Heng JI, Nguyen L, Castro DS, Zimmer C, Wildner H, Armant O, Skowronska-Krawczyk D, Bedogni F, Matter JM, Hevner R, Guillemot F. (2008) Neurogenin 2 controls cortical neuron migration through regulation of Rnd2. Nature, 455(7209):114-8. [NCBI PubMed Entry]
  21. Zhao X, Heng JI, 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, 10(6):643-53. [NCBI PubMed Entry]
  22. Heng JI, Moonen G, Nguyen L (2007) Neurotransmitters regulate cell migration in the telencephalon. European Journal of Neuroscience, 26(3):537-46. [NCBI PubMed Entry]
  23. Nguyen L, Besson A, Heng JI, Schuurmans C, Teboul L, Parras C, Philpott A, Roberts JM, Guillemot F (2006) p27Kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes & Development, 20(11):1511-24. [NCBI PubMed Entry]
  24. Ge W, He F, Kim KJ, Blanchi B, Coskun V, Nguyen L, Wu X, Zhao J, Heng JI, Martinowich K, Tao J, Wu H, Castro D, Sobeih MM, Corfas G, Gleeson JG, Greenberg ME, Guillemot F, Sun YE (2006) Coupling of cell migration with neurogenesis by proneural bHLH factors. Proceedings of the National Academy of Sciences USA, 103(5): 1319-24. [NCBI PubMed Entry]
  25. Hand R, Bortone D, Mattar P, Nguyen L, Heng JI, Guerrier S, Boutt E, Peters E, Barnes AP, 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, 48(1):45-62. [NCBI PubMed Entry]
Back To Top