{"id":48,"date":"2016-09-12T19:30:59","date_gmt":"2016-09-12T19:30:59","guid":{"rendered":"https:\/\/lab.research.sickkids.ca\/robinson\/?page_id=48"},"modified":"2017-10-31T12:56:46","modified_gmt":"2017-10-31T12:56:46","slug":"research","status":"publish","type":"page","link":"https:\/\/lab.research.sickkids.ca\/robinson\/research\/","title":{"rendered":"Research"},"content":{"rendered":"

[vc_row][vc_column][vc_custom_heading text=”Research Interests:” font_container=”tag:h2|font_size:22|text_align:left|color:%23000000″ use_theme_fonts=”yes”][vc_column_text]<\/p>\n

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[\/vc_column_text][vc_column_text]Dr. Lisa Robinson\u2019s research actively explores the mechanisms whereby the cell surface levels and functions of membrane-anchored endothelial chemokines are regulated. More recently, Dr. Robinson and her team have been studying how the neuronal repellents, Slit and Roundabout, inhibit leukocyte chemotaxis and adhesion, and platelet function. Dr. Robinson\u2019s research group combines a wide range of methodologies, including biochemistry, cell biology, advanced microscopy, molecular biology, and animal experimentation, to comprehensively study a variety of research questions.<\/p>\n

As a clinician-scientist and paediatric nephrologist, Dr. Robinson\u2019s ultimate goal is to use the new knowledge generated from her research to transform the care that children with kidney disease receive. Understanding the pathogenesis and complex biology that underlies inflammatory renal disease is critical for the design of innovative, rational therapies.[\/vc_column_text]

<\/div>[\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=”Current Projects:” font_container=”tag:h2|font_size:22|text_align:left|color:%23000000″ use_theme_fonts=”yes”][vc_column_text]<\/p>\n
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[\/vc_column_text][vc_column_text]Slit-Robo Signalling in\u00a0Vascular Inflammation<\/strong><\/p>\n

Complications of atherosclerosis, especially heart attack and stroke, are the leading cause of morbidity and mortality in the Western world. Atherosclerosis is characterized by progressive accumulation of immune cells known as monocytes, vascular smooth muscle cells (VSMC), and platelets within diseased arteries. Monocytes in the endothelial space differentiate to form macrophages, and engulf lipoproteins, transforming into lipid-laden foam cells that secrete pro-inflammatory mediators. Despite the success of lipid-lowering agents, atherosclerosis still often progresses in at-risk individuals. Instead, our goal is to determine if we can simultaneously target multiple pathologic cell migration signals and foam cell formation within the vasculature, using both in vitro<\/em> and animal experimental methods.<\/p>\n

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Regulation of Leukocyte-Endothelial Interactions<\/strong><\/p>\n

The immune system operates through a series of complex interactions between circulating white blood cells and the inner cell lining of blood vessels (the endothelium). Small, secreted proteins, called chemokines, provide traffic signals that attract white blood cells to the vascular endothelium, which allows for the immune system to patrol the area and provide protection from pathogens. One chemokine \u2013 fractalkine (FKN) \u2013 when bound to its receptor on white blood cells triggers a cascade of events that results in increased white blood cell adhesion. The goal of this study is to understand how FKN signalling occurs in endothelial cells, and the functional consequences of this pathway.<\/p>\n

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Preventing Chronic Kidney Disease after Acute Kidney Injury<\/strong><\/p>\n

Acute kidney injury (AKI) resulting from ischemia-reperfusion injury (IRI) is a major cause of late renal failure due to progressive renal fibrosis (scarring). To date, there are no effective treatments. Early after AKI, platelets and immune cells infiltrate the kidney; but how these events cause later fibrosis is still unknown. Our aim through this study is to determine how platelets and immune cells act to promote early kidney IRI and influence later progressive renal fibrosis, with the goal of opening the door to new therapeutic strategies against AKI and chronic kidney disease (CKD).<\/p>\n

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Normothermic ex vivo<\/em> Kidney Perfusion<\/strong><\/p>\n

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The best treatment for a patient in end-stage renal disease (ESRD) is kidney transplantation. However, due to a global shortage, grafts from living donors and from standard criteria deceased donors are not always readily available for patients in need. As an alternative, donor kidneys from extended criteria donation (ECD) and donation after circulatory death (DCD) are increasingly being used. Current techniques for kidney transplantation involve hypothermic preservation of the kidney, but this may result in injury to the\u00a0graft. This study investigates the safety and feasibility of preserving kidneys under normothermic, physiological conditions\u00a0ex vivo<\/em>\u00a0in a porcine model.<\/p>\n<\/div>\n

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<\/div>[\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=”Selected Publications:” font_container=”tag:h2|font_size:22|text_align:left|color:%23000000″ use_theme_fonts=”yes”][vc_column_text]<\/p>\n
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[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/4″][vc_column_text]Continuous normothermic ex vivo<\/em> kidney perfusion is superior to brief normothermic perfusion following static cold storage in donation after circulatory death pig kidney transplantation.<\/a>[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]American Journal of Transplantation, 2017[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]PDF<\/a>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/4″][vc_column_text]Chemokine signalling enhances CD36 responsiveness towards oxidized low-density lipoproteins and accelerates foam cell formation.<\/a>[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]Cell Reports, 2016[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]PDF<\/a>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/4″][vc_column_text]Recombinant N-terminal Slit2 inhibits TGF-\u03b2-induced fibroblast activation and renal fibrosis.<\/a>[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]Journal of the American Society of Nephrology, 2016[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]PDF<\/a>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/4″][vc_column_text]The neurorepellent, Slit2, inhibits post-adhesion stabilization of monocytes to vascular endothelial cells and early monocyte recruitment in atherosclerosis.<\/a>[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]The Journal of Immunology, 2015[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]PDF<\/a>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/4″][vc_column_text]Cytoskeletal confinement of CX3CL1 limits its susceptibility to proteolytic cleavage by ADAM10.\u00a0<\/a>[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]Molecular Biology of the Cell, 2014[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]PDF<\/a>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/4″][vc_column_text]Slit2 prevents neutrophil recruitment and renal ischemia reperfusion injury in mice.<\/a>[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]Journal of the American Society of Nephrology,\u00a02013[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]PDF<\/a>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”2\/4″][vc_column_text]The Cell Motility Modulator Slit2 is a Potent Inhibitor of Platelet Function.<\/a>[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]Circulation, 2012[\/vc_column_text][\/vc_column][vc_column width=”1\/4″][vc_column_text]PDF<\/a>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column]

<\/div>[\/vc_column][\/vc_row][vc_row][vc_column][\/vc_column][\/vc_row][vc_row][vc_column][vc_custom_heading text=”All Publications:” font_container=”tag:h2|font_size:22|text_align:left|color:%23000000″ use_theme_fonts=”yes”][vc_column_text]<\/p>\n
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[\/vc_column_text][vc_column_text]A comprehensive list of Dr. Robinson’s publications.<\/a>[\/vc_column_text]

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If you are interested in becoming\u00a0involved in the Robinson Lab’s research projects, please contact us:<\/strong><\/p>\n

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