​July 2023
Stem cell groups' summer outing to the Peak District, just 20 min drive from the lab (one of the advantages of living in Sheffield).












July 2023
Farewell dinner for Ingrid, who started in the lab 5.5 years ago (first as a PhD student and then a postdoc) and did some fantastic work (funded by LPT, CCLG and Neuroblastoma UK) on modelling the initiation of the paediatric tumour neuroblastoma using hESCs. 

















June 2023
New preprint from the lab (led by Fay) looking at the role of Notch, a key developmental signalling pathway in the specification and differentiation of the progenitors of the spinal cord and vertebral column: https://www.biorxiv.org/content/10.1101/2023.06.16.545269v1 

March 2023
Combined St Patrick’s day celebrations with Antigoni passing her viva (3rd AT lab PhD student to reach this stage!)-so well deserved given the incredible work she has done during her PhD. 













September 2022
Antigoni's preprint (see below) has just become a newly published article in eLife: https://elifesciences.org/articles/74263#info. Fay's reviews on the clinical applications of axial progenitors (https://www.sciencedirect.com/science/article/pii/S0012160622001233?via%3Dihub) and anteroposterior patterning of hESC-derived neural crest cells (https://portlandpress.com/biochemsoctrans/article/50/1/499/230641/Shaping-axial-identity-during-human-pluripotent) were also out earlier this year.

September 2021
Antigoni's first project in the lab (when she started as an Erasmus student in our lab a few years back) is now out as a preprint on Biorxiv: https://www.biorxiv.org/content/10.1101/2021.09.24.461516v1.full. In this we dissect the links between the function of the key transcription factor (responsible for posterior embryonic body development), human neuromesodermal progenitor (NMP) induction and posterior neural crest (NC) specification using hPSC differentiation as a model. We found that:
(i) disruption of NMP induction/mesoderm competence via knockdown of TBXT abolishes the acquisition of a posterior axial identity by NC cells but not CNS spinal cord pre-neural progenitors 
(ii) TBXT mediates early posteriorisation in NMPs/prospective NC cells in conjunction with WNT signalling by directly orchestrating an open chromatin landscape in HOX clusters 
(iii) control of trunk HOX gene expression/posteriorisation in NMP-derived CNS spinal cord pre-neural progenitors appears to be TBXT/WNT-independent and programmed after NMP differentiation primarily under the action of FGF signalling.
This work indicates the existence of two distinct phases of posterior axial identity control: (i) an early NMP-based that involves the TBXT/WNT-driven establishment/fixing of a HOX-positive, posterior character in uncommitted progenitors followed by its “transmission” to their downstream trunk NC derivatives and, (ii) a later one, which is based on the FGF-driven sculpting of a posterior axial identity in cells transiting toward a spinal cord neural fate, post-NMP differentiation:















March 2021
Matt's PhD paper is now out in Development: https://dev.biologists.org/content/early/2021/02/26/dev.194415. In this we describe a method for producing in the petri dish motor neurons that correspond to the lower part (thoracic) of the spinal cord using human pluripotent stem cells. These cells offer a promising tool for modelling neurodegenerative conditions affecting the spinal cord and also a potential cell therapy source for treating spinal cord injuries. Our review on the biology of the progenitors of these motor neurons (as well as other cell types that make up the body trunk) has also just been published  in Development: https://dev.biologists.org/content/148/4/dev180612.

Aug 2020
Tom's latest paper (=November's bioRxiv preprint) focusing on the in vitro generation of vagal neural crest and enteric nervous system progenitors is now published in Stem Cell Reports: https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(20)30301-5. The work is a result of a great collaboration with Conor McCann, Nihil Thapar and Alan Burns from the  UCL Great Ormond Street Institute of Child Health and forms the basis of our joint efforts to develop a stem cell-based therapy to treat Hirschsprung disease (see below). For more details see also here.

Aug 2020
Our lab is featuring in the first of the new series of ResearchFocus interviews by our funders Children's Cancer and Leukaemia Group (CCLG): https://www.cclg.org.uk/news/research-focus-dr-anestis-tsakiridis

July 2020
We are grateful to the MRC and its Populations and Systems Medicine Board, for funding our grant application 'Developing a human pluripotent stem cell-based strategy for treating Hirschsprung's disease'. The project is a collaboration with colleagues from the UCL Great Ormond Street Institute of Child Health and aims to develop a stem cell therapy for the treatment of Hirschsprung disease, a life-threatening enteric neuropathy that affects approximately 1 in 5000 live births, making it one of the most common congenital diseases affecting the gut.
 
January 2020
Neuroblastoma UK's new blog feature on how we use hPSC-derived trunk neural crest cells to model Neuroblastoma in the petri dish: https://www.neuroblastoma.org.uk/news/2020/1/16/dr-anestis-tsakiridis
 
November 2019
Tom's new paper (in collaboration with Peter Andrews here in Sheffield and also Conor McCann, Nikhil Thapar and Alan Burns from the UCL Great Ormond Street Institute of Child Health) on the role of retinoic acid in generating vagal neural crest cells from hES cells is now out on bioRxiv: https://www.biorxiv.org/content/10.1101/819748v1
We also describe the accelerated in vitro generation of functional human enteric neural progenitors and enteric neurons/glia. We next hope to exploit these findings for the development of a cell-based therapy to treat aganglionic gut disorders such as Hirschsprung's disease.

January 2019
Our group together with the Peter Andrews lab (Centre for Stem Cell Biology, Biomedical Science Department) are now part of a network of 7 partner universities that has been awarded an EU grant of almost €7 million. The project (CONNECT: “Connecting neural networks: Nervous-system-on-Chip Technology”), which was launched last week with a kick-off meeting in Eindhoven, Netherlands, brings together a wide range of research disciplines aiming to develop a new type of organs-on-a-chip (OoC) for modelling Parkinson’s disease.

OoC is a case with tubes, called microfluidic channels, which allows experiments to be done on living cells. Well-known examples of OoCs are liver-on-a-chip and heart-on-a-chip. In vitro experiments involving OoCs offer the advantage that they are easy to repeat: unlike animal models such as mice, OoCs are very similar to each other. This makes it much easier to repeat an experiment. The hope is that with a complete understanding of an organ, researchers will be able to produce a perfectly functioning OoC, in which new drugs can be tested on a large scale.

Eindhoven University of Technology (TU/e) is leading this new research consortium aiming at developing a nervous-system-on-a-chip (NoC), which could be used, for example, to test new drugs against Parkinson's disease. It could also help reduce the number of animal experiments, bringing both ethical and practical benefits. The NoC will connect different types of nerve cells to each other, through three compartments, aiming to mimic the “natural” connections that exist between the central and peripheral nervous system, in the human body. This will in turn, allow the study of the transport of specific proteins that travel in the nervous system and are associated with Parkinson's disease. The role of the University of Sheffield groups in this project is to produce the appropriate peripheral nervous system components, such as enteric neurons, using human pluripotent stem cells (hPSCs) as a starting material. Other partners include the University of Luxembourg which will be involved in growing organoids from hPSCs i.e. structures that mimic specific human brain cells whereas optical and electrophysiological analysis of the resulting nerve cells will be done by KU Leuven (Belgium) and the Erasmus MC (Netherlands) respectively. AALTO University (Finland) will help with the choice of materials and electrodes for the construction of the NoC while the Oxford Parkinson Disease Center will provide cells from Parkinson's patients for testing. The TU/e researchers will take care of the design and realisation of the NoC.
The project will open the door to personalized medicine approaches involving the rapid testing of candidate drugs directly on patient cells. This will also accelerate the development of new medicines, something that is currently desperately needed, given that a new drug has an average development time of 10 to 12 years and costs about 1.6 billion Euros.