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Staff Profile

Professor Matthew Collin

Professor of Haematology

  • Telephone: +44 (0) 191 208 7785
  • Personal Website: https://research.ncl.ac.uk/hilab/research/
  • Address: Institute of Clinical and Translational Research
    Newcastle University
    Framlington Place
    Newcastle upon Tyne
    NE2 4HH
    UK
Background


Academic Haematologist with research focus on haematopoiesis and the immune system

Principal Investigator, Haematopoiesis and Immunogenomics Lab, Newcastle University

Honorary Consultant Haematologist at Newcastle Hospitals NHS Foundation Trust

https://orcid.org/0000-0001-6585-9586



 

Research

Research themes

1.  Mapping ontogeny in the human immune system

This theme of research is focussed on the origin of human myeloid cells, specifically monocytes, dendritic cells and macrophages, in health and inflammation. Following the argument that ontogeny is intimately related to function, understanding the origin of myeloid cell lineages is the key to developing therapeutic interventions.  Major challenges remain including: solving the origin of human dendritic cells from bone marrow progenitors; devising an accurate description of the homeostasis of human tissue macrophages; and mapping the relative contributions of dendritic cell and monocyte lineages to inflammatory lesions.  The aim is to resolve fully the populations of tissue dendritic cells and macrophages in humans, creating a platform for high-resolution mapping of changes induced by inflammation.

2. Modulation of haematopoiesis and immunity by germline and somatic mutation

Haematopoiesis is regulated by the coordinated action of many extrinsic factors, signal transduction molecules and transcription factors that shape the destiny of blood lineages.  Defects in these impact upon monocyte, dendritic cell and macrophage development.  Our work has uncovered a series of germline mutations in GATA2, IRF8, IKZF1 and other factors that are critical for normal development of myeloid cells.  Mutation in these genes leads to clinically significant illness including immunodeficiency, infection and neoplasia.  GATA2 mutation is not only a cause of late onset immunodeficiency but emerges as one of the most prevalent genetic predispositions to myelodysplasia and leukaemia.

Somatic mutation arises in all tissues with increasing age. Gain of function mutations in the MAP kinase pathway drive histiocytosis, a group of rare inflammatory neoplastic disorders that illustrate the potential of minor abnormal clones of haematopoiesis to wreak severe multi-system disease.  The envelope of this model is being explored in a range of more prevalent acquired immune and inflammatory disorders with poorly understood aetiology.  Age-related somatic mutation in the haematopoietic system may also lead to subtle but pervasive dysregulation of immunity manifest as an increased risk of common disorders such as cardiovascular disease. This research theme also extends the principle that  germline and somatic variation cause genetic pathology through common loci.  

Finally, somatic mutation also provides a powerful tool to dissect ontogeny in the haematopoietic system, synergising with the first research theme.  The ability to exploit this is amplified enormously by the advent of single cell genomic technology

3. Dissection of the mechanisms of immune responses in tissues

Events in the lymph node, where T cells are primed, take centre-stage in conventional models of immunity.  However, in human pathology, non-lymphoid tissues are almost always the basis of diagnostic pathology.  An important link with clinical haematopoietic stem cell transplantation, is the study of graft versus host disease (GVHD).  The aim is to develop an detailed and sophisticated description of the immune activation of inflammatory infiltrates in GVHD, to reveal new targets for therapy.  This work will provide greater insight into the role of monocytes, macrophages and dendritic cells in the effector phase of all immune responses tissues.

Teaching

Undergraduate, masters and post-graduate supervision

Undergraduate medical lectures in haematology

Publications