A5020083398- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Blood groups and transfusion
- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
- Ultrasound and Hyperthermia Applications
- Platelet Disorders and Treatments
- Lymphatic System and Diseases
- Angiogenesis and VEGF in Cancer
- Retinal Diseases and Treatments
- Atherosclerosis and Cardiovascular Diseases
- Virus-based gene therapy research
- Adenosine and Purinergic Signaling
- Vagus Nerve Stimulation Research
- Mosquito-borne diseases and control
- Neurological and metabolic disorders
- Wheat and Barley Genetics and Pathology
- SARS-CoV-2 and COVID-19 Research
- Apelin-related biomedical research
- COVID-19 and healthcare impacts
- Glaucoma and retinal disorders
- Iron Metabolism and Disorders
- Corneal surgery and disorders
- Immune cells in cancer
- RNA regulation and disease
Sunnybrook Research Institute
2016-2021
University of Toronto
2014-2021
Health Sciences Centre
2020-2021
Sunnybrook Health Science Centre
2016-2021
Physical Sciences (United States)
2018
Sunnybrook Hospital
2017
Stefan University
2015
University of Minnesota
2015
Lunenfeld-Tanenbaum Research Institute
2010-2015
Mount Sinai Hospital
2010-2012
Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Disease-associated mutations have been described in the genes encoding regulators factor H, membrane cofactor protein, B, and I. In this study, we show two independent cohorts of aHUS patients that deletion closely related genes, H-related 1 (CFHR1) 3 (CFHR3), increases risk aHUS. Amplification analysis sequencing genomic DNA three affected individuals revealed a chromosomal approximately 84 kb RCA...
Hemolytic uremic syndrome (HUS) is a disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Recent studies have identified factor H–associated form of HUS, caused gene mutations that cluster in the C-terminal region complement regulator H. Here we report how three (E1172Stop, R1210C, R1215G; each latter two independent cases from different, unrelated families) affect protein function. All cause reduced binding to central component C3b/C3d...
Glaucoma is a leading cause of blindness, afflicting more than 60 million people worldwide. Increased intraocular pressure (IOP) due to impaired aqueous humor drainage major risk factor for the development glaucoma. Here, we demonstrated that genetic disruption angiopoietin/TIE2 (ANGPT/TIE2) signaling pathway results in high IOP, buphthalmos, and classic features glaucoma, including retinal ganglion degeneration vision loss. Eyes from mice with induced deletion Angpt1 Angpt2 (A1A2Flox(WB)...
Significance Reducing vascular leakage and stabilizing the endothelium through activation of angiopoietin (ANGPT)–TIE2 receptor tyrosine kinase pathway is a promising therapeutic strategy for diseases. ANGPT2 one two major ligands TIE2 receptor. Uniquely, possesses an agonistic role in lymphatic endothelium, but acts as competitive antagonist blood endothelium. The molecular basis opposing actions these beds poorly understood. Here we demonstrate that absence VEPTP expression confers agonist...
Summary The complement inhibitor Factor H has three distinct binding sites for C3b and heparin, but in solution uses specifically the most C-terminal domain, i.e. short consensus repeats (SCR) 20 ligand interaction. Two novel monoclonal antibodies (mABs C14 C18) that bind to domain SCR completely blocked interaction of with ligands C3b, C3d, heparin endothelial cells. In contrast, several mAbs N-terminus middle regions molecule showed no or minor inhibitory effects when assayed by...
Many of the complement regulatory genes within RCA cluster (1q32) have arisen through genomic duplication and resulting high degree sequence identity is likely to predispose gene conversion events. The highest between for factor H (CFH) five H-related proteins--CFHL1, CFHL2, CFHL3, CFHL4, CFHL5. CFH mutations are associated with atypical hemolytic uremic syndrome (aHUS). In Newcastle cohort 157 aHUS patients we identified in 25 families or individuals. Eleven these independent either...
Atypical hemolytic uremic syndrome is a disease that characterized by microangiopathic anemia, thrombocytopenia, and acute renal failure. Mutations in the complement regulator factor H are associated with inherited form of disease, >60% mutations located within C terminus H. The C-terminus H, represented short consensus repeat 19 (SCR19) SCR20, harbors multiple functions; consequently, this study aimed to examine functional effects clinically reported these SCR. Mutant proteins (W1157R,...
Urinary concentrating ability is central to mammalian water balance and depends on a medullary osmotic gradient generated by countercurrent multiplication mechanism. Medullary hyperosmolarity protected from washout exchange efficient removal of interstitial fluid resorbed the loop Henle collecting ducts. In most tissues, lymphatic vessels drain excess back venous circulation. However, renal medulla devoid classic lymphatics. Studies have suggested that fenestrated ascending vasa recta (AVRs)...
Significance The efficacy of immunotherapy in Alzheimer’s disease is limited, partly because antibodies, administered peripherally, have poor access to the brain. Focused ultrasound (FUS) with microbubbles allows passage antibodies from blood In a mouse model disease, blood, and without FUS, reduced amyloid pathology. contrast, FUS was required deliver sufficient hippocampus effectively promote neurogenesis. Neurogenesis, regenerative process involved memory functions, impaired disease....
Focused ultrasound delivery of a selective TrkA agonist rescues cholinergic function in mouse model Alzheimer’s disease.
Defective complement regulation results in hemolytic uremic syndrome (HUS), a disease that is characterized by microangiopathy, thrombocytopenia, and acute renal failure causes endothelial cell damage. For characterization of how defective relates to the pathophysiology, role regulator factor H also mutant protein was studied on surface human umbilical vein cells. The 145-kD purified homogeneity, from plasma patient with HUS, who heterozygous for gene mutation G3587T, which introduces stop...
Background and Purpose— Recent evidence suggests great potential of metabolically targeted interventions for treating neurological disorders. We investigated the use endogenous ketone body β-hydroxybutyrate (BHB) as an alternate metabolic substrate brain in acute phase ischemia because postischemic hyperglycemia glucose metabolism elevation compromise functional recovery. Methods— delivered BHB (or vehicle) 1 hour after ischemic insult induced by cortical microinjection endothelin-1...
Efficient disease-modifying treatments for Alzheimer disease, the most common form of dementia, have yet to be established. Gene therapy has potential provide long-term production therapeutic in brain following a single administration. However, blood-brain barrier poses challenge gene delivery adult brain. We investigated transduction efficiency and immunological response non-invasive gene-delivery strategies mouse model amyloidosis. Two emerging technologies enabling across were used...
Hemolytic uremic syndrome (HUS) is a disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Recent studies have identified factor H–associated form of HUS, caused gene mutations that cluster in the C-terminal region complement regulator H. Here we report how three (E1172Stop, R1210C, R1215G; each latter two independent cases from different, unrelated families) affect protein function. All cause reduced binding to central component C3b/C3d...