Centre for Clinical Brain Sciences

Dr Paul de Sousa

Dr Paul de Sousa is a Reader who is interested in the development of stem cell-based treatments for neurodegenerative diseases.

Dr Paul de Sousa

Reader

  • Centre for Clinical Brain Sciences
  • Associate Researcher – MRC Centre for Regenerative Medicine
  • Chief Scientific Officer – Roslin Cells Ltd

Contact details

Biography

Following undergraduate and graduate degrees at the University of Toronto (BSc 1982-86; MSc 1986-88) and University of Western Ontario (PhD; 1989-93) in zoology and the developmental biology of amphibian and mouse egg maturation and early embryogenesis, and postdoctoral research at the University of Toronto, Pennsylvania and Western Ontario in mammalian embryogenesis, I joined the Roslin Institute in 1998 as a Group Leader in embryo biotechnology focused on animal cloning by somatic cell nuclear transfer, parthenogenesis and human embryonic stem cell isolation.

In 2005 I joined the University of Edinburgh as a Senior Lecturer focused on development of understanding and technology to isolate, grow, and characterise human pluripotent stem cells as isolated from embryos or induced by genetic manipulation. I also co-founded a not-for-profit company, Roslin Cells Ltd., to manufacture and clinically deliver human stem cell based therapies.

I joined CCBS in 2015 to apply this knowledge in the development of stem cell-based treatments for neurodegenerative diseases.

Research summary

Human pluripotent stem cells as isolated from embryos or induced by genetic manipulation of adult cells have remarkable capacity for growth and to be turned into all of the cells that make our bodies unmatched by any other cells. These are important to enable their use to understand development and disease, or be used to screen for new drugs or as a source of cells to replace disease and damaged tissues.

Our research is about developing and using the tools to grow, purify and characterise human pluripotent stem cells so they are safe, effective and in the quantities needed for their intended application. This is especially important if cells derived from them are to be transplanted into the brain to repair loss or degenerating brain cells, or if they are to be used to discover new drugs to treat the symptoms of disease.

Stem cells in culture
A colony of human embryonic stem cells stained for a regulatory protein called Nanog .

Research aims and areas of interest

Our laboratory has three aims addressing the use of human pluripotent stem cells in applications generally and in the treatment of neurodegenerative diseases specifically.

1. Understand the intrinsic and extrinsic factors that control being a pluripotent stem cell and impact on their safety as a source of cells for transplantation

We are interested in the role and interplay of genes subject to epigenetic regulation by the cellular environment, and the susceptibility of these cells and derivatives to protein missfolding pathologies. Specifically we are focused on mechanisms modulating genomic hydroxymethylation as a means to express or repress gene expression controlling pluripotency and lineage commitment, the role of constitutive prion prions and susceptibility to spontaneous or transmitted prion disease.

2. Developing the tools to grow, purify and characterise human pluripotent stem cells

We are interested in supportive biochemicals and materials and the biophysical properties which distinguish these cells from others. This includes small molecules, biodegradable or modulatable polymers and scalable biophysical cell purification technology which does not require recognition of cell-associated markers or ligands.

3. Applying the aforementioned knowledge and tools to use human embryo and induced pluripotent stem cell derived cells for the discovery and implementation of new treatments for neurodegenerative disease, specifically Huntingtons Disease

Through Roslin Cells Ltd, we have contributed to the establishment of an internationally competitive capacity in human pluripotent stem cell manufacturing for research and clinical applications, as well as research and clinical grade induced and embryonic stem cells. One flagship project uses clinical grade cells and capacity to progress a human pluripotent stem cell based therapy for Huntingtons Disease.

Collaborators

  • Prof Mark Bradley, Department of Chemistry, University of Edinburgh. Identification of polymers providing a supportive substrate for hESC growth
  • Profs. Anne Rosser & Steve Dunnett , The Brain Repair Group, School of Biosciences, Cardiff University
  • Dr Mark Head, National CJD Research & Surveillance Unit
  • Prof Tarek Fahmy, Department of Biomedical Engineering, Yale University. Affinity Targeted Paracrine Stimulation in stem cell culture and regenerative medicine

Sources of funding

  • Chief Scientist Office (Scotland)
  • Medical Research Council (MRC)
  • Scottish Enterprise (Edinburgh and Lothian)
  • European Union (FP7 program)
  • Biotechnology and Biological Sciences Research Council (BBSRC)
  • Engineering and Physical Sciences Research Council (EPSRC)

Other information

Roslin Cells Ltd is the managing entity of the European Bank for Induced Stem Cells, a large European public-private partnership project supported jointly by the Innovative Medicines Initiative (IMI) and members of the European Federation of Pharmaceutical Industries and Associations (EFPIA). Its mission is to provide a standardised source of disease representative human induced pluripotent stem cells. I lead the workpackage for the establishment of the foundational collection of hiPSC lines.

Roslin Cells Ltd is a partner in an EUFP7 funded programme, RepairHD to develop a human pluripotent stem cell based therapy for Huntingtons disease founded on the use of its clinical grade human embryonic stem cells. I lead the workpackage for translation of research protocols into Good Manufacturing Practice.