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?

 

Piper M, Gronostajski RM, Messina G (2019) Nuclear Factor One X in development and disease. Trends in Cell Biology 29, 20-30. DOI: 10.1016/j.tcb.2018.09.003

Oishi S, Harkins D, Kurniawan N, Kasherman M, Harris L, Zalucki O, Gronostajski R, Burne T, Piper M (2019) 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

Zalucki O, Harris, L, Harvey TJ, Harkins D, Widagdo J, Oishi S, Matuzelski E, Yong X, Schmidt H, Anggono V, Burne THJ, Gronostajski RM, Piper M (2019) NFIX-mediated inhibition of neuroblast branching regulates migration within the adult mouse ventricular-subventricular zone. Cerebral Cortex, 29, 3590-3604. DOI: 10.1093/cercor/bhy233

Meier S, Kurniawan N, Milne M, Kasherman M, Delogu A, Piper M, Coulson E (2019) The p75 neurotrophin receptor is required for the survival of neuronal progenitors and normal formation of the basal forebrain, striatum, thalamus and neocortex. Development, 146: dev181933. DOI: 10.1242/dev.181933

Johnson B, Kumar R, …Piper M, Gecz J, Jolly L (2019) Partial loss of USP9X function leads to a male neurodevelopmental and behavioral disorder converging on Transforming Growth Factor b signalling. Biological Psychiatry, in press. DOI: 10.1016/j.biopsych.2019.05.028

Harris L, Zalucki O, Clement O, Fraser J, Matuzelski E, Oishi S, Harvey TJ, Burne TH, Heng JI, Gronostajski RM, Piper M (2018) Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression. Development, 145:1-12. DOI: 10.1242/dev.155689

Harris L, Zalucki O, Gobius I, McDonald H, Osinski J, Harvey TJ, Essebier A, Vidovic D, Gladwyn-Ng I, Burne TH, Heng JI, Richards LJ, Gronostajski RM, Piper M (2016) Transcriptional regulation of intermediate progenitor cell generation during hippocampal development. Development, 143, 4620-4630. DOI: 10.1242/dev.140681

Lim J, Donahoo A, Bunt J, Edwards T, Fenlon L, Liu Y, Zhou J, Moldrich R, Piper M, Gobius I, Bailey T, Wray N, Kessaris N, Poo M, Rubenstein J, Richards L (2015) EMX1 regulates NRP1-mediated wiring of the mouse anterior cingulate cortex. Development,142: 3746-3757. DOI: 10.1242/dev.119909

Heng YHE, Zhou B, Harris L, Harvey T, Smith A, Horne E, Martynoga B, Andersen J, Achimastou A, Cato K, Richards L, Gronostajski R, Yeo G, Guillemot F, Bailey T, Piper M (2015) NFIX regulates proliferation and migration within the murine SVZ neurogenic niche. Cerebral Cortex 25:3758-3778. DOI: 10.1093/cercor/bhu253

Piper M, Barry G, Harvey TJ, McLeay R, Smith AG, Harris L, Mason S, Stringer BW, Day BW, Wray NR, Gronostajski RM, Bailey TL, Boyd AW, Richards LJ (2014) NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development. The Journal of Neuroscience, 34:2921-2930. DOI: 10.1523/JNEUROSCI.2319-13.2014

Heng YHE, McLeay R, Harvey TJ, Smith AG, Barry G, Cato K, Plachez C, Little E, Mason S, Dixon C, Gronostajski RM, Bailey TL, Richards LJ, Piper M (2014) NFIX regulates neural progenitor cell differentiation during hippocampal morphogenesis. Cerebral Cortex, 24; 261-279. DOI: 10.1093/cercor/bhs307

View all publications from Dr Piper on ORCiD

Group Head

Staff

Students

June 2020

Well done to Maria, who has formally been awarded her PhD. Champagne time!

Congratulations to Alex, who has also been awarded her PhD!

Sabrina got excellent comments back from her thesis examiners, so is also very close to getting over the PhD line. Well done Sabrina!

May 2020

Sazia was recently awarded a travel bursary from FENS to attend their 2020 meeting. Well done Sazia!

Congratulations to James for submitting his PhD thesis, and to Maria for resubmitting hers. Fingers crossed both!!

April 2020

Well done to Raul, who was awarded a scholarship to do his PhD. Raul will be working on a project with our lab and that of Jo Bowles, looking at the molecular control of spermatogenesis

During this coronavirus hiatus, the lab has been madly writing and submitting papers. A big pat on the back to everyone in the lab!

March 2020

A huge well done to Sabrina, who submitted her PhD thesis recently. A massive effort, and hopefully it will sail through the process quickly

Congrats to Sazia, who was awarded a travel scholarship from SBMS to attend the upcoming FENS meeting in Europe

February 2020

Raul achieved First Class Honours for his work on NFIX in the testis. Well done Raul!

Maria has had her review on Usp9x in development and disease published. Good work.

Sabrina has also had her excellent work on Sotos syndrome published in Genes, Brain and Behavior. Excellent stuff!

January 2020

Sabrina Oishi, a PhD student in the Piper lab recently was accepted to the 2020 STEM Policy Internship at the Australian Academy for Technological Sciences and Engineering (ATSE), in Melbourne. This is a 3-month internship, and was very competitive, so well done Sabrina!

Sabrina also won the 2019 SBMS HDR student Research Excellence Award.

Sabrina, as well as Maria Kasherman, another PhD student from the Piper lab, also won imaging awards at the Faculty of Medicine Research Excellence Awards night in December last year.

Well done to James, whose paper on shared targets for NFIA and NFIX was accepted in The Cerebellum.

Well done to Laura, who obtained a HDR scholarship, and who joins us in January to start her PhD.

Raul’s first first author paper came out in its final form. Well done Raul!


December 2019

Well done to Laura, who got a First Class Honours mark!

Well done also to Raul for finishing up his Honours project with us and the Bowles lab

Our collaborative paper with the Penzes lab (Northwestern) was recently published in Neuron. This paper got some good publicity; see below!

November 2019

Well done to Sabrina, who breezed through her M3. Good luck with the thesis writing Sabrina!

Well done to Belal, from the Ng lab, who’s paper was recently accepted into Human Molecular Genetics

October 2019

Well done to Laura and Sandy for finishing up their Honours projects; both did amazingly well.

Congrats to Maria, who has taken up some part time work at the SBMS Imaging facility.

We recently had a paper with our great collaborators including the Richards lab accepted in the American Journal of Medical Genetics.

Well done to Raul, Danyon, Laura and James. Our paper with the wonderful Josephine Bowles was recently accepted in the Journal of Molecular Histology.  

September 2019

Mike was lucky enough to snare a UQ Award for Excellence in HDR Supervision (Emerging Advisor Award). Thanks to all of the fantastic HDR students I have had the honour of working with. Check out the video.

Our paper with our wonderful collaborators in the Coulson lab on the role of the p75 neurotrophin receptor in cortical development is now available here.

August 2019

Check out Mike, Sherry and Lizzie discussing chronic diseases for the Faculty of Medicine.

Well done to Sonja, for absolutely smashing her M3 presentation, and for having her first paper accepted in Development. An awesome effort!

July 2019

Congratulations to James, who has taken a job at the SBMS imaging facility. We look forward to interacting with him productively in coming years!

June 2019

Our manuscript on Usp9x in human patients is now available online.

May 2019

Our paper with the Simmons lab on a novel model for autism is now available online from EBioMedicine.

Well done to Sabrina and Maria, who contributed to a lovely piece of collaborative work with DrLachlan Jolly (University of Adelaide) and Professor Stephen Wood (Griffith University), that was just accepted for publication in Biological Psychiatry.

April 2019

Well done to Cathy Zhang (Simmons lab), for her lovely work on a novel mouse model for autism that has just been accepted in EBioMedicine. We hope this is the first in a long list of collaborative works with the Simmons lab.

Well done to Danyon, who passed his M1. Onwards and upwards!

March 2019

Congrats to Diana, who has been conferred her doctorate from our august institute. Well done!!

Well done to Laura and Sandy, who did very well in the Honours proposal seminars.

February 2019

Congrats to Di, who submitted the corrections for her thesis this month.

Maria sailed through her last milestone presentation; well done you!

Check out the UQ FoM blog featuring Mike discussing Rare Disease Day.

January 2019

Congratulations to Sabrina, whose work on Malan syndrome was recently published in EBioMEdicine. Her work made the cover of this issue!

Welcome also to Laura, who recently joined the lab for her Honours project. Good luck throughout the year Laura.


December 2018

Well done to James, who was awarded the best student poster presentation at the recent EMBL Australia Postgraduate Symposium.

Sonja and Sabrina were both winners at the recent ANS conference. Sonja won best poster, and Sabrina won third prize for the best image competition. Well done also to Sazia and Sabrina for their great talks at ANS.

November 2018

Congratulations to Sabrina, who won the 2018 EMBL Australia Postgraduate Symposium SciArt Competition.

Well done to Raquelle, who received a well-deserved First Class Honours for 2018. Great effort Raquelle!

October 2018

Well done to Lachlan, Sabrina and James, all of whom won prizes at the recent Queensland ANZSCDB meeting, held at the Translational Research Institute. Awesome effort from the Piper lab!

Well done again to Sabrina, who recently won a Poster Award at the 9th SBMS International Post-grad Symposium, for her work on the role of NFIX in macrocephaly

September 2018
Well done to Oressia, as well as Lachlan, Tracey, Danyon and Sabrina, as their paper was recently accepted for publication in the prestigious journal, Cerebral Cortex. An awesome effort!
 
Well done to Sazia, who was selected to present her work at the recent ComBio conference, that was held in Sydney.

August 2018

Well done to Sazia, who has been selected to give an oral presentation at the 2018 ComBio conference, that will be held in Sydney in September.

Congratulations to Oressia, who recently had a paper published in BMC Neuroscience.

July 2018

Well done to James, who passed his M3 this month.

Sabrina has been selected to participate in the 2018 IMNIS MedTech-Pharma Program. Well done Sabrina!

June 2018

Lachlan and Oressia’s paper on NFIX in the adult hippocampus is now published in Development. Well done all!

http://dev.biologists.org/content/145/3/dev155689

Maria was awarded a travel bursary to attend the 2018 ISSCS meeting in Melbourne. Well done Maria!

Mike was awarded the Emerging Leader gong from ANZSCDB for 2018

https://twitter.com/ANZSCDB/status/1004525736949112832

May 2018

 A big welcome to Dr Sazia Sharmin, who joins us as a UQ Development Fellow this month.

 Well done to Raul, who completed his Summer Scholarship with us this month.

 Congratulations to Lachlan and Oressia, whose paper on identifying cell cycle parameters appeared in the latest issue of The Journal of Molecular Histology

 https://link.springer.com/article/10.1007/s10735-018-9761-8

 Mike, and the team from First 5 Forever (State Library of Queensland), collaborated on a video promoting early childhood literacy last year (Little Moments, Big Impact). This video recently won an award at the A corto di libri international film contest.  Well done all!

https://medicine.uq.edu.au/article/2018/05/neuroscientist-puts-childhood-literacy-show

 April 2018

Welcome to Danyon, who is joining us for a PhD. Danyon will be investigating the role of NFI proteins in adult neurogenesis.

A huge well done to Diana, who submitted her PhD thesis on the role of NFIX in ependymal cell formation this month. An excellent effort, that included two first author manuscripts, and a first author book chapter. Thanks also to Tracey for her contribution to getting Di over the line.

Sabrina waltzed through her M2 this month.  The committee were very impressed!  Well done Sabrina

March 2018

Raquelle did a wonderful job for her Honours proposal talk. Well done Raquelle!

A great effort from Elise and Sabrina, who won bursaries to attend the ISDN meeting in Japan later this year.

Thank you to the Brisbane Marketing and Development Board, who awarded Mike a Trailblazer grant to attend the upcoming ISDN meeting in Nara, Japan. It should be a fantastic conference!

Well done to Elise, who sailed through her M2 this month. The committee were very impressed and excited with the presentation.

Feb 2018

Congratulations to Diana, Raul and Tracey, whose work on the role of NFIX in ependymal cell development was recently published in Neural Development

          https://neuraldevelopment.biomedcentral.com/articles/10.1186/s13064-018-0099-4

Exciting news for Elise, Sabrina and Maria, who have all been accepted into the upcoming meeting for the International Society for Developmental Neuroscience, which will be held in Nara (Japan) in May. 

          http://www.isdn-conference.elsevier.com

Jan 2018

Another sterling effort by Lachlan, Oressia and Sabrina, whose paper on a method for identifying adult neural stem cells in the hippocampus, was recently published in Developmental Dynamics

http://onlinelibrary.wiley.com/doi/10.1002/dvdy.24545/full

Well done to Danyon, who was awarded a First Class Honours for his project last year. Danyon is also joining us for his PhD project.

Welcome to Raquelle Ludwig, who is doing Honours with us this year.

Congratulations to Raul, who got married late last year!

The lab was fortunate to get funding from a number of sources last year; thanks to all those who contributed to this, and to the funding bodies for supporting our research.

We received a Discovery Project Grant from the ARC, with our wonderful collaborator, A/Prof Tom Burne. This work aims to analyse the transcriptional regulation of brain size.

In collaboration with A/Prof Helen Cooper, who was the lead investigator, we also obtained a Project Grant from the NHMRC to investigate the development of hydrocephalus.

We were also fortunate enough to obtain an Explorer Award from the Simons Foundation Autism Research Initiative to study the role of Usp9x in the development of this disorder.

https://www.sfari.org/2017/12/06/sfari-2017-explorer-awardees-announced/


2017

Well done to Elise on the acceptance of her first publication as lead author. Elise's work, detailing the role of NFIX in spinal cord development, was recently accepted to Developmental Biology. Congratulations also to Lachlan and Danyon, who contributed to this work.

Congratulations to Diana, Lachlan and Oressia, who contributed to a paper recently accepted to Brain and Neuroscience Advances. This work was performed in collaboration with the Richards lab at the QBI. Great job all.


Alex recently had a paper accepted for publication in the journal Methods.  This work details her work on the prediction of target genes from transcription factor binding data. Well done Alex!


The lab team, along with wonderful our collaborators Dr. Fiona Simpson (Diamantina Institute), Dr. Glen Boyle (QIMR) and Dr. Ben Panizza (PA Hospital), was fortunate enough be awarded an Enabling Grant from the Australian Skin and Skin Cancer Research Centre for our work in developing an in vitro model for studying perineural invasion of squamous cell carcinomas of the head and neck. We look forward to working with a PhD student in Fiona’s lab, Priscila Oliveira De Lima, who will be driving this work.

https://medicine.uq.edu.au/article/2017/08/collaboration-investigates-possible-immunotherapy-rare-melanomas


Congratulations to James and Sabrina, both of whom were accepted into training courses run through the Neuroscience School of Advanced Studies. Both got to spend a week in Northern Italy learning about the latest techniques in neuroscience. Sabrina also got a travel scholarship from the Graduate School to fund her trip.


Well done to Lachlan and Tracey, who contributed to a recently published study investigating the expression of NFI proteins within the adult brain. Images from the paper made the front cover of the August 1st 2017 issue of The Journal of Comparative Neurology

http://onlinelibrary.wiley.com/doi/10.1002/cne.24239/full


Elise recently attended the recent EMBL Australia PhD course held at Monash University. Places were scarce for this, so well done Elise!


Congratulations to Lachlan, who recently graduated with a PhD, and who has taken up a prestigious, 4-year post doctoral position at the Crick Institute in London in the lab of Prof. Francois Guillemot. Lachlan’s most recent work on adult neurogenesis was recently published in Developmental Dynamics

http://onlinelibrary.wiley.com/doi/10.1002/dvdy.24545/full


James, Alex and Tracey had their work detailing the expression of NFIX within the postnatal cerebellum published recently in the July 2017 Issue of Brain Structure and Function. A job well done all!

https://link.springer.com/article/10.1007/s00429-016-1340-8


Well done to Mitch, who has finished his PhD and has now moved to the States to do a post doc.  Mitch had two recent papers, which appeared in eBioMedicine and The International Journal of Cancer.

http://www.ebiomedicine.com/article/S2352-3964(17)30017-8/fulltext

http://onlinelibrary.wiley.com/doi/10.1002/ijc.30603/full


Swati had her final piece of work from the lab published in the February 2017 Issue of The Journal of Molecular Histology. Well done to Swati and Tracey on this manuscript!

https://link.springer.com/article/10.1007/s10735-016-9702-3

 

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