A5079103617- Hemoglobinopathies and Related Disorders
- Venous Thromboembolism Diagnosis and Management
- Central Venous Catheters and Hemodialysis
- Blood Coagulation and Thrombosis Mechanisms
- Blood groups and transfusion
- Platelet Disorders and Treatments
- Blood disorders and treatments
- Vascular Malformations and Hemangiomas
- Renal Diseases and Glomerulopathies
- Vascular anomalies and interventions
- Cell Adhesion Molecules Research
- Iron Metabolism and Disorders
- Axon Guidance and Neuronal Signaling
- Acute Myeloid Leukemia Research
- Erythrocyte Function and Pathophysiology
- Angiogenesis and VEGF in Cancer
- Traumatic Brain Injury and Neurovascular Disturbances
- Immunodeficiency and Autoimmune Disorders
- Genomics and Rare Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neuroblastoma Research and Treatments
- Childhood Cancer Survivors' Quality of Life
- Hemophilia Treatment and Research
- Genetics and Neurodevelopmental Disorders
- Apelin-related biomedical research
Western University
2020-2025
London Health Sciences Centre
2020-2025
Hospital for Sick Children
2009-2022
University of Toronto
2009-2018
SickKids Foundation
2012-2018
National Research Council Canada
2012
St. Michael's Hospital
2011-2012
Biotechnology Research Institute
2012
Canadian Blood Services
2012
University of Kansas
2011
Summary Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia attributed to disturbances in five different red cell membrane proteins. We performed retrospective study of 166 children with HS and describe the clinical phenotype according genotype. In 160/166 (97%) disease‐causing mutation was identified. Pathogenic variants ANK1 , SPTB SLC4A1 SPTA1 were found 49%, 33%, 13% 5% patients. Children ‐HS had mildest phenotype, showing highest haemoglobin ( P < 0·001), lowest...
In inflammatory diseases, circulating neutrophils are recruited to sites of injury. Attractant signals provided by many different chemotactic molecules, such that blockade one may not prevent neutrophil recruitment effectively. The Slit family secreted proteins and their transmembrane receptor, Robo, repel axonal migration during CNS development. Emerging evidence shows inhibiting the activation Rho-family GTPases, Slit2/Robo also inhibit other cell types toward a variety factors in vitro...
Neutrophils recruited to the postischemic kidney contribute pathogenesis of ischemia-reperfusion injury (IRI), which is most common cause renal failure among hospitalized patients. The Slit family secreted proteins inhibits chemotaxis leukocytes by preventing activation Rho-family GTPases, suggesting that members this might modulate recruitment neutrophils and resulting IRI. Here, in static microfluidic shear assays, Slit2 inhibited multiple steps required for infiltration into tissue....
Neutrophils are involved in the inflammatory responses during atherosclerosis. Human neutrophil peptides (HNPs) released from activated neutrophils exert immune modulating properties. We hypothesized that HNPs play an important role neutrophil-mediated cardiovascular atherosclerosis.We examined of endothelial-leukocyte interaction, platelet activation, and foam cell formation vitro vivo. demonstrated stimulation human coronary artery endothelial cells with clinically relevant concentrations...
Vascular injury and atherothrombosis involve vessel infiltration by inflammatory leukocytes, migration of medial vascular smooth muscle cells to the intimal layer, ultimately acute thrombosis. A strategy simultaneously target these pathological processes has yet be identified. The secreted protein, Slit2, its transmembrane receptor, Robo-1, repel neuronal in developing central nervous system. More recently, it been appreciated that Slit2 impairs chemotaxis leukocytes toward diverse...
In atherosclerosis, chemokines recruit circulating mononuclear leukocytes to the vascular wall. A key factor is CX(3)CL1, a chemokine with soluble and transmembrane species that acts as both chemoattractant an adhesion molecule. Thromboxane A(2) its receptor, TP, are also critical atherogenesis by promoting inflammation consequent leukocyte recruitment. We examined effects of TP stimulation on processing function using CX(3)CL1-expressing human ECV-304 cells primary endothelial cells....
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To assess the safety and efficacy of rapamycin in treating children with vascular tumours malformations.We performed a retrospective review at large tertiary care paediatric centre to using treat malformations. Response therapy was defined by patient-reported symptom improvement, radiological reduction size lesions, and/or improvement laboratory parameters.Forty-two patients (7 35 malformations) have been treated rapamycin. Despite 33 42 being diagnosed first year life, median age initiating...
Mercaptopurine is a cornerstone of maintenance chemotherapy in childhood acute lymphoblastic leukemia (ALL). Its cytotoxic effects are mediated by 6-thioguanine nucleotides (TGNs) incorporation into lymphocyte DNA. Thiopurine methyltransferase (TPMT) inactivates mercaptopurine, and deficiency resulting from genetic variants increases TGN exposure hematopoietic toxicity. Although mercaptopurine-dose reduction reduces toxicity risk without compromising relapse rate patients with TPMT...
Classification of inherited bone marrow failure syndromes (IBMFSs) according to clinical and genetic diagnoses enables proper adjustment treatment. Unfortunately, 30% patients enrolled in the Canadian Inherited Marrow Failure Registry (CIMFR) with features suggesting hereditability could not be classified a specific syndromic diagnosis. We analyzed outcome hematopoietic stem cell transplantation (HSCT) unclassified IBMFSs (uIBMFSs) factors associated outcome. Twenty-two uIBMFSs 70 underwent...
Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, situated near α-globin cluster. Haploinsufficiency NPRL3, either by deletion or pathogenic variant, associated with variable phenotype focal epilepsy, without malformations cortical development, known decreased penetrance. Case Description: This work details diagnostic odyssey neurotypical...
Lu, Amy D. MD; Geerlinks, Ashley V. Ganesan, Saptharishi L. MD, DM; Hsia, Cyrus Hedley, Benjamin PhD; Tole, Soumitra MD Author Information