Apresentação
Sara M. Rankin (Imperial College London, UK)
Over her career Prof Rankin has made significant contributions in the field of biomedical sciences, working in a number of distinct disease areas. During her PhD she discovered that flavonoids (plant-derived polyphenolic substances found notably in red wine), vitamin E and vitamin C could all inhibit the oxidative modification of lipoproteins, a key step in atherogenesis. This work led to the idea that drinking red wine was good for heart disease, but more importantly highlighted how aspects of diet, other than cholesterol consumption, could contribute to the rate and extent of disease progression. During her postdoc at CRUK Prof Rankin identified a unique cross talk in signalling pathways emanating from distinct growth factor receptors (G-protein coupled and tyrosine kinase) and regulated by the actin cytoskeleton (3). She was the first to show that growth factors such as PDGF could regulate the activation of focal adhesion proteins including focal adhesion kinase, paxillin and p130 cas, thereby regulating cell shape and adhesion. Prof Rankin published a seminal series of research papers describing the 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. This work was paradigm shifting and represents a significant contribution to our current understanding of fundamental neutrophil biology which others have since built on. Prof Rankin showed that the rapid mobilization of granulocytes from the bone marrow represents the first step in the trafficking of these cells to sites of inflammation. She identified specific cytokines and chemokines that regulate the mobilization of neutrophils, eosinophils and monocytes from the bone marrow in the course of specific inflammatory reactions, such as allergic asthma. Moreover, she identified the adhesion molecules and signalling pathways regulating this process.
Specifically she was the first to show a role for phosphatidyl inositol 3’ kinase in leukocyte trafficking in vivo, an important finding as drugs targeting this pathway were subsequently developed by several Big Pharma companies to treat inflammatory diseases. In recent years Prof Rankin has focused on investigating stem cell mobilization from the bone marrow. She provided critical data on structure activity relationships for CXCR4 antagonists that was submitted to FDA and contributed to the AMD3100 being licensed for stem cell mobilization. Further she made the fundamental discovery that different molecular mechanisms regulate the mobilization of haematological and non-haematological stem cells from the bone marrow. This seminal work led to the discovery of a combination therapy for the selective mobilization of mesenchymal stem cells from the bone marrow.
This invention has the potential for translation in the field of regenerative medicine for the treatment of a range of diseases, including heart disease and musculoskeletal injuries and was patented in Dec 2008, with patent applications applied for in Europe and the USA in 2010.
Over her career Prof Rankin has made significant contributions in the field of biomedical sciences, working in a number of distinct disease areas. During her PhD she discovered that flavonoids (plant-derived polyphenolic substances found notably in red wine), vitamin E and vitamin C could all inhibit the oxidative modification of lipoproteins, a key step in atherogenesis. This work led to the idea that drinking red wine was good for heart disease, but more importantly highlighted how aspects of diet, other than cholesterol consumption, could contribute to the rate and extent of disease progression. During her postdoc at CRUK Prof Rankin identified a unique cross talk in signalling pathways emanating from distinct growth factor receptors (G-protein coupled and tyrosine kinase) and regulated by the actin cytoskeleton (3). She was the first to show that growth factors such as PDGF could regulate the activation of focal adhesion proteins including focal adhesion kinase, paxillin and p130 cas, thereby regulating cell shape and adhesion. Prof Rankin published a seminal series of research papers describing the 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. This work was paradigm shifting and represents a significant contribution to our current understanding of fundamental neutrophil biology which others have since built on. Prof Rankin showed that the rapid mobilization of granulocytes from the bone marrow represents the first step in the trafficking of these cells to sites of inflammation. She identified specific cytokines and chemokines that regulate the mobilization of neutrophils, eosinophils and monocytes from the bone marrow in the course of specific inflammatory reactions, such as allergic asthma. Moreover, she identified the adhesion molecules and signalling pathways regulating this process.
Specifically she was the first to show a role for phosphatidyl inositol 3’ kinase in leukocyte trafficking in vivo, an important finding as drugs targeting this pathway were subsequently developed by several Big Pharma companies to treat inflammatory diseases. In recent years Prof Rankin has focused on investigating stem cell mobilization from the bone marrow. She provided critical data on structure activity relationships for CXCR4 antagonists that was submitted to FDA and contributed to the AMD3100 being licensed for stem cell mobilization. Further she made the fundamental discovery that different molecular mechanisms regulate the mobilization of haematological and non-haematological stem cells from the bone marrow. This seminal work led to the discovery of a combination therapy for the selective mobilization of mesenchymal stem cells from the bone marrow.
This invention has the potential for translation in the field of regenerative medicine for the treatment of a range of diseases, including heart disease and musculoskeletal injuries and was patented in Dec 2008, with patent applications applied for in Europe and the USA in 2010.