Dr Anestis Tsakiridis

Anestis Tsakiridis

Vice-Chancellor’s Fellow
Department of Biomedical Science
The University of Sheffield
E 225, Alfred Denny building
Western Bank
Sheffield S10 2TN
United Kingdom

Tel: +44 114 222 2367
Email: a.tsakiridis@sheffield.ac.uk

CSCB Logo
Bateson Member Staff Logo

General

Brief career history

  • 2016-present: Group Leader (Vice-Chancellor’s Fellow)
  • 2009-2015: Post-doctoral researcher, MRC Centre for Regenerative Medicine, University of Edinburgh (Advisor: Prof. Val Wilson)
  • 2006-2009: Post-doctoral researcher, Institute for Stem Cell Research, University of Edinburgh (Advisor: Prof. Josh Brickman)
  • 2002-2006: PhD, University of Edinburgh (Advisors: Prof. Lesley Forrester, Prof. Josh Brickman)
  • 2001-2002: MSc (Res), University of Edinburgh
  • 1998-2001: BSc (Hons), University of Edinburgh

Research interests

My group aims to understand how cells adopt different identities during embryonic development and disease. This knowledge is essential for the precise control of cell behavior and the generation of clinically relevant cell populations from human pluripotent stem cells (hPSCs). We are particularly interested in dissecting the events leading to the “birth” of the cell types which make up the posterior (thoracic and lumbosacral) spinal cord. In the embryo, these are produced by Neuromesodermal Progenitors (NMPs), a bipotent cell population which also gives rise to paraxial mesoderm, the precursor of the body musculature and skeleton.

We have recently succeeded in deriving human NMPs (hNMPs) from hPSCs by “mimicking” the signalling environment of their niche in vivo. We are now utilizing these cells as a starting point for answering the following questions:



  1. How do pluripotent cells differentiate into NMPs?
  2. How do NMPs differentiate into spinal cord and paraxial mesoderm?
  3. What are the optimal culture conditions promoting the generation of different posterior spinal cord cell types (e.g. motor neurons, oligodendrocytes, astrocytes)? How do they differ from their anterior counterparts?

Full publications

Research

Various studies in different vertebrate organisms have revealed the existence of a bipotent stem cell-like population which drives embryonic axis elongation through the coordinated production of posterior neuroectoderm (PNE) and paraxial mesoderm (PXM), the building blocks of the spinal cord and trunk skeletal muscle/skeleton respectively. In the mouse embryo these Neuromesodermal Progenitors (NMPs) reside in the late primitive streak (PS) area and later the tailbud, sites which exhibit high WNT/FGF signalling activity.

Research image 1

NMPs are marked by the co-expression of the transcription factors (TFs) Brachyury (T(BRA)) and SOX2, which are indicative of a mesodermal and neural character respectively. Apart from being an excellent model for studying the mechanisms underlying cell fate (neuroectoderm vs mesoderm) decision-making, NMPs also comprise an attractive source for generating spinal cord cells and skeletal muscle in vitro. These cell types are currently difficult to derive from pluripotent stem cells (PSCs) probably because conventional directed differentiation protocols are heavily influenced by the idea that mesodermal and neuroectodermal lineages arise from separate precursors and ignore the existence of NMPs. Thus the ability to maintain pure cultures of NMPs in vitro and define the optimal conditions for their differentiation would be highly desirable.

However, the limited availability of micro-dissected embryonic NMPs has been a major obstacle to the study of both their biology and the molecular events driving their differentiation. To address this issue we have recently defined the optimal culture conditions for the induction of functional adherent NMPs from mouse and, importantly, human PSCs (hPSCs) involving treatment with the WNT agonist CHIR99021 (CHIR) and FGF2. Under these conditions, the majority of the resulting cultures consist of T(BRA)+SOX2+ NMPs after 48-72 hours of treatment.

We now aim to use hPSC-derived NMPs as a tractable in vitro system to address the following questions:

  1. How do embryonic cells proceed from pluripotency to bipotency?
  2. What are the molecular determinants of a NM bipotent state?
  3. How do NMPs generate PNE and PXM cells
  4. What are the optimal culture conditions for the efficient production of posterior (thoracic and lumbosacral) spinal cord cell types from NMPs?
  5. Are “altered” NM bipotent states linked to disease?

Our research employs hPSC culture and differentiation, CRISPR/Cas9-based genome editing, next generation sequencing and high content/live imaging.

Funding:

  • The University of Sheffield,
  • Biotechnology and Biological Sciences Research Council (BBSRC)
  • The Royal Society
  • Children's Cancer and Leukaemia Group/Little Princess Trust

Members:

  • Joseph Kelleher (postdoc)
  • Erin Stout (MSc student)
  • Emma Brudenell (Msc student)
Teaching

Undergraduate and postgraduate taught modules

Level 3:

  • BMS326 Modelling Human Disease
  • BMS369 Laboratory Research Project

Masters (MSc):

  • BMS6055 Modelling Human Disease
Opportunities

There's currently no positions available in my lab at the moment. However, I am welcome to speculative applications.

To express interest, please feel free to email me a copy of your CV:

Selected publications

Journal articles