Regenerative Pharmacology

Professor Sara Rankin - Head of Group

The bone marrow is a rich source of stem cells and also serves as a reservoir for mature granulocytes. Our research is focused on understanding how bone marrow cells populate and repair tissues in health and disease. Specifically my group aims to identify the factors and molecular mechanisms that regulate the mobilization of leukocytes and stem cells from the bone marrow and their recruitment to sites of inflammation and the role of the bone marrow in the clearance of granulocytes. Understanding these pathways at a molecular level will ultimately lead to the development of novel therapies to reduce inflammation or promote tissue regeneration.

The Mobilization of Leukocytes from the Bone Marrow

The bone marrow contains a large reserve of granulocytes that are rapidly mobilized into the blood during inflammatory episodes in diseases, such as asthma. This mobilization is necessary to provide the large numbers of leukocytes recruited to sites of inflammation. We have identified the cytokines and chemokines that regulate the mobilization of discrete populations of leukocytes during specific inflammatory diseases. Further we have determined the role of adhesion molecules and signalling pathways in these processes. The aim of these studies is to identify novel therapeutic targets for the treatment of inflammatory diseases. 

 

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CXCR4 and Neutrophil Biology

Neutrophils are an essential component of the innate immune system playing a key role in defence against bacterial, fungal, and viral infections. We have discovered a critical role of the chemokine receptor CXCR4, both in terms of retention of mature neutrophils in the bone marrow reserve and the trafficking of senescent neutrophils back to the bone marrow for clearance. We are currently investigating the functional importance of these pathways in terms of homeostasis and in the context of inflammatory diseases.

Regenerative Pharmacology

The adult bone marrow contains a number of discrete populations of stem cells, including the haematological stem cells that form blood and the non haematological stem cells (endothelial progenitor cells and mesenchymal stem cells) that facilitate tissue repair. Our studies have shown that distinct molecular mechanisms regulate the mobilization of these discrete populations of stem cells. Moreover we have discovered a drug regimen that selectively mobilizes stem cells the non-haematological stem cells dramatically boosting their numbers in the blood. This novel therapy has been patented and we are currently investigating whether this and/or other pharmacological interventions can promote tissue regeneration.

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Selected Publications

Rankin SM. (Aug 2010). The bone marrow: a site of neutrophil clearance. J Leukoc Biol. 88:241-251.

Jones CP; Pitchford SC; Lloyd CM; Rankin SM. (Dec 2009). CXCR2 mediates the recruitment of endothelial progenitor cells during allergic airways remodeling. Stem Cells. 27:3074-3081. DOI.

Pitchford SC; Furze RC; Jones CP; Wengner AM; Rankin SM. (9 Jan 2009). Differential mobilization of subsets of progenitor cells from the bone marrow. Cell Stem Cell. 4:62-72.

Wengner AM; Pitchford SC; Furze RC; Rankin SM. (10 Oct 2007). The co-ordinated action of G-CSF and ELR+CXC chemokines in neutrophil mobilisation during acute inflammation. Blood.

Martin C; Burdon PC; Bridger G; Gutierrez-Ramos JC; Williams TJ; Rankin SM. (Oct 2003). Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity. 19:583-593.

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