Piper Group - Neural stem cells in development and disease

Research directions

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 disease processes caused by abnormal NSC differentiation (Figure 1).

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?

 

For my full publication track record, please visit my ORCID site

  1. Davila, R. A. et al. Deletion of NFIX results in defective progression through meiosis within the mouse testis. Biol Reprod, doi:10.1093/biolre/ioac049 (2022).
  2. Fane, M. E. et al. Reciprocal Regulation of BRN2 and NOTCH1/2 Signaling Synergistically Drives Melanoma Cell Migration and Invasion. J Invest Dermatol, doi:10.1016/j.jid.2020.12.039 (2022).
  3. Yaghmaeian Salmani, B. et al. Selective requirement for polycomb repressor complex 2 in the generation of specific hypothalamic neuronal subtypes. Development 149, doi:10.1242/dev.200076 (2022).
  4. Kasherman, M. A. et al. Abnormal Behavior and Cortical Connectivity Deficits in Mice Lacking Usp9x. Cereb Cortex 31, 1763-1775, doi:10.1093/cercor/bhaa324 (2021).
  5. Kojic, M. et al. Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype. Nat Commun 12, 2678, doi:10.1038/s41467-021-22888-5 (2021).
  6. Weissleder, C. et al. Reduced adult neurogenesis is associated with increased macrophages in the subependymal zone in schizophrenia. Mol Psychiatry, doi:10.1038/s41380-021-01149-3 (2021).
  7. Johnson, B. V. et al. Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor beta Signaling. Biol Psychiatry 87, 100-112, doi:10.1016/j.biopsych.2019.05.028 (2020).
  8. Shim, W. J. et al. Conserved Epigenetic Regulatory Logic Infers Genes Governing Cell Identity. Cell Syst 11, 625-639 e613, doi:10.1016/j.cels.2020.11.001 (2020).
  9. Yoon, S. et al. Usp9X Controls Ankyrin-Repeat Domain Protein Homeostasis during Dendritic Spine Development. Neuron 105, 506-521 e507, doi:10.1016/j.neuron.2019.11.003 (2020).
  10. Oishi, S. et al. Heterozygosity for Nuclear Factor One X in mice models features of Malan syndrome. EBioMedicine 39, 388-400, doi:10.1016/j.ebiom.2018.11.044 (2019).
  11. Zalucki, O. et al. NFIX-Mediated Inhibition of Neuroblast Branching Regulates Migration Within the Adult Mouse Ventricular-Subventricular Zone. Cereb Cortex 29, 3590-3604, doi:10.1093/cercor/bhy233 (2019).
  12. Harris, L. et al. Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression. Development 145, doi:10.1242/dev.155689 (2018).
  13. Harris, L. et al. Transcriptional regulation of intermediate progenitor cell generation during hippocampal development. Development 143, 4620-4630, doi:10.1242/dev.140681 (2016).

Group Head

Staff

Students

April 2024

Ben passed his first Progress Review with flying colours. Well done mate!

Lucy also did extremely well in her Honours proposal seminar, and she is poised for a big year ahead

Well done to both Mikki and Justin for completing their Honours projects. A great effort!

Welcome to Cooper, who joined us as a PhD scholar this research quarter.

Well done also to Raul who submitted his PhD thesis this month. Almost there now!!

February 2024

A big thank you to Hallie Naumann, who worked with us over the summer. And a big hello to Linda Luo, who will be in the lab for semester 1.

Ben’s paper has now been published in Neuroscience Letters. Check it out!

November 2023

Congratulations to Cooper, who obtained a First Class Honours mark, and who won an award for his oral presentation.

Well done also to Mikki and Justin, who did fantastic jobs with their Honours proposal seminars.

October 2023

Congrats to Laura who conferred her PhD!

Well done to Ben, who had his review on SETD2 function accepted to Journal of Cell Science this month.

Congratulations to Cooper and Fiona, who both handed in their Honours theses recently.

Congratulations also to Raul, who sailed through his PR3.

August 2023

Well done to Mikki and Justin, who both submitted their Honours proposal this month.

Laura received great comments on her thesis, and successfully did her viva. Congratulations Laura!

Ben resubmitted his review to The Journal of Cell Science this month. Fingers crossed now.

July 2023

Congratulations to Laura, who submitted her thesis for review! Exciting times!

Brad’s manuscript in Bioinformatics was accepted this month; well done Brad.

Welcome to Mikki Doonan and Justin Jones, who have joined us for Honours at the mid-year intake.

June 2023

Well done to Cooper, who got excellent marks for his Honours proposal and oral presentation.

Ben had a busy month, submitting a first author paper from his Honours work, and a first author review. Fingers crossed!

The lab was successful in receiving a grant from the RTW Charitable Foundation, to continue our work on Malan syndrome.

April 2023

Our collaborative with the Thakker group on models of Marshall-Smith syndrome has been published in JBMR Plus. Check it out!!

Well done to Cooper and Fiona on their Honours presentations this month. Both did well!

Laura was recently awarded a travel grant from the Company of Biologists to attend the IBRO conference later this year. Great news, and very well deserved.

March 2023

Congratulations to Laura, who excelled in her Progress Review 3 presentation. Very impressive!

Our collaborative paper on Marshall-Smith syndrome with our Oxford collaborators, Raj Thakker and Kreepa Kooblall, was recently accepted to JBMR Plus. Well done to Oressia and Lachlan for their contributions to this paper.

Cooper submitted an excellent Honours proposal this month; well done!

January 2023

Amazing work from Ben Mitchell, who was awarded an RTP to commence his PhD in the lab this month. Welcome Ben!

If you would like to make a tax deductible donation to neural stem cell research, please contact med.advancement@uq.edu.au. Thank you for your support.

Find out more about our research environment and how to apply to do a short or long-term research project with us.