We specialise in imaging microcirculatory events in a number of diseased and healthy organs using a technique called intravital microscopy. Our research focuses on identifying inflammatory disturbances, vasculoprotective mechanisms and stem cell homing. Experimental models of ischaemia-reperfusion injury, acute renal injury, colitis and chronic liver disease are routinely utilised.
Our research is focussed on identifying the pathophysiological mechanisms underlying ischemia-reperfusion (I/R) injury, particularly the microvascular disturbances involved and the role of inflammatory neutrophils, platelets and lymphocytes. Furthermore we are developing strategies, particularly the use of adult bone marrow derived stem cells, that may be of therapeutic benefit following I/R injury. Haematopoietic (HSC) and mesenchymal stem cells (MSC) can migrate to injured tissues and help in tissue repair. However, the events that govern their recruitment to injured tissue microcirculation in vivo, and whether their local tissue presence following systemic transplantation can be enhanced, are unclear.
Our research focuses on examining the molecular adhesive events involved in HSC or MSC recruitment to different vascular beds following injury, including the liver, gut, kidney and cremaster muscle. The vasculoprotective effects mediated by stem cells within the local inflamed microcirculation are also determined. The cross-talk between different circulating cell populations, particularly with platelets, is also being directly monitored using animal models of thrombosis e.g., laser induced injury. Inflammatory and stem cell trafficking is monitored predominantly by state-of-the-art confocal based intravital microscopy which allows real-time and dynamic microcirculatory images to be captured in vivo. This technique allows numerous microcirculatory disturbances to be quantified, including the various events of the adhesion cascade (rolling/adhesion/transmigration) and also changes in vascular integrity.
- Kavanagh DPJ, Yemm AI, Alexander JS, Frampton J and Kalia N (2013) Enhancing the adhesion of haematopoietic precursor cell integrins with hydrogen peroxide increases recruitment within murine gut. Cell Transplantation – IN PRESS
- Kavanagh DPJ, Yemm AI, Zhao Y, Frampton J and Kalia N (2013) SDF-1a enhances haematopoietic stem cell homing to injured gut and is subsequently associated with reduced leukocyte recruitment. PLoS One 8:e59150
- White RL, Nash G, Savage COS and Kalia N (2013) Modulating the adhesion of haematopoietic stem cells with chemokines to enhance their recruitment to the ischaemically injured murine kidney. PloS One 8:e66489
- Aldridge V, Garg A, Davies N, Bartlett DC, Youster J, Beard H, Kavanagh DP, Kalia N, Frampton J, Lalor PF and Newsome PN (2012) Human mesenchymal stem cells are recruited to injured liver in a ß1-integrin and CD44 dependent manner. Hepatology 56(3):1063-73
- Oo YT, Banz V, Kavanagh D, Withers D, Humphreys E, Lee-Turner L, Reynolds G, Kalia N, Swain MG, Lane PJL, Adams DH and Eksteen B (2012) Synergy between CXCL10 and CCL20 Mediates recruitment of interleukin 17 producing T cells to the liver. J Hepatol 57(5):1044-51
- Kavanagh DP and Kalia N (2011) Hematopoietic stem cell homing to injured tissues. Stem Cell Rev 7:672-82
- Kavanagh DPJ, Durant LE, Crosby HA, Lalor PF, Frampton J, Adams DH and Kalia N (2010) Haematopoietic stem cell recruitment to the hepatic microcirculation following murine ischemia-reperfusion injury is dependent on an a 4 b 1 integrin interaction. Gut 59:79-87
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