Lesley Forrester

Director of Postgraduate Studies

Background

  • Professor of Stem Cell Differentiation, MRC Centre for Regenerative Medicine (2012-present)
  • Reader, Centre for Inflammation Research (2007-2012
  • LRF Senior Lecturer, John Hughes Bennett Laboratory, University of Edinburgh (1998-2007)
  • MRC Senior Fellowship, Centre for Genome Research, University of Edinburgh (1993-1998)
  • EMBO Postdoctoral Research Fellow, Samuel Lunenfeld Research Institute, Toronto, Canada (1989-1993)
  • ICRF Postdoctoral Research Fellow, University of Edinburgh (1986-89)
  • PhD: University of Edinburgh (1986)

Responsibilities & affiliations

CRM Director of Postgraduate Studies

Deanery of Clinical Sciences Depute Director of Postgraduate Studies

College of Medicine and Veterinary Medicine Academic Misconduct Officer

Undergraduate teaching

3rd year:Clinical Immunology and Haematology

4th year: Regenerative Medicine;  Reproductive Biology

Postgraduate teaching

Depute Director MRes Regenerative Medicine and Tissue Repair

CRM Director Postgraduate Studies

Current PhD students supervised

Alisha May

Telma Ventura

Past PhD students supervised

Gurman Pall               

Alistair Watt               

Anna Krassowska                  

Tim Chevassut           

Anestis Tsakiridis      

Richard Axton            

Sabrina Gordon-Keylock

Katrin Buerger

Lindsay Fraser

Madina Kara  

Caoxin Huang            

Rui Ma                       

Maria Kydonaki                     

Sharmin Haidera                    

Cheng-Tao Yang                    

Martha Lopez Yrigoyen

Research summary

Haematopoietic cell differentiation

Diseases of the blood system such as leukaemia and anaemia are often treated using cell therapies such as bone marrow transplantation and blood transfusion. However, these procedures are reliant on a limited donor supply and are complicated by transmissible infections. The long-term goal of our research is to replace these procedures with haematopoietic stem cells and red blood cells that have been produced in the laboratory from pluripotent stem cells. We are studying the molecular processes involved in the production of blood cells from pluripotent stem cells so we can optimise the production of cells with the appropriate function.

Aims and areas of interest

Haematopoietic progenitor cells and mature blood cells, including macrophages, granulocytes, mast cells and erythrocytes can be generated in vitro from human pluripotent stem cells (hPSCs). However, it has proven challenging to manufacture fully functional cells that are comparable to the cells that are generated in the body. For example, it has not been possible to produce fully functional haematopoietic stem cells (HSCs) that are capable of robust reconstitution of the haematopoietic system and the erythrocytes that are produced in vitro from hPSCs are immature and they fail to enucleate efficiently.

 

1. Functional HSCs from human PSCs.

To understand why it has proven so difficult to generate fully functional reconstituting HSCs from PSCs, we have taken a single cell sequencing approach to define the transcriptome of the haematopoietic progenitor cells that can be generated in vitro. By comparing these to HSCs that arise in vivo we aim to uncover the molecular pathways that are missing in PSC-derived progenitors. That knowledge will be used to refine differentiation culture conditions and/or to genetically programme cells by the activation of endogenous transcription factors using CRISPR/CAS9 approaches.

2. Maturation of erythroid cells.

Erythroid cells mature within erythroid island (EI) niche that consists of a central macrophage surrounded by developing erythroid cells. To uncover the molecular processes involved in erythroid maturation, we have developed an in vitro model for the EI niche using genetically programmed iPSC-derived macrophages. We are using this model to identify novel pathways associated with RBC maturation that could be applied to the manufacture of RBCs in vitro and to identify novel therapies for anaemia.

3. Macrophages from human PSCs

We have developed an efficient protocol to generate monocytes and mature macrophages from human PSCs pluripotent stem and have established a number of collaborations to study the role of macrophages in disease including liver fibrosis, arthritis and cancer.

Current project grants

2020-2023. MRC (MR/T013923/1). Identification and characterisation of the molecular components associated with the human erythroid island niche in normal and abnormal erythropoiesis. (£780K)
2018-2021. BBSRC (BB/S002219/1). An inducible CRISPR/dCAS9 strategy for directed differentiation of pluripotent stem cells. (ca.£700K).

View all 43 publications on Research Explorer

  • Jo Mountford, Scottish National Blood Transfusion Service
  • Jan Frayne, University of Bristol
  • Jim Beiker, ICAHN School of Medicine, New York
  • Pablo Menendez, School of Medicine, University of Barcelona
  • Gavin Wright, Sanger Institute.
  • Stuart Forbes, CRM
  • Jeff Pollard, Centre for Reproductive Health
  • Mariola Kurowska-Stolarska, University of Glasgow