Claire L. Harris
A5022159555- Complement system in diseases
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- interferon and immune responses
- Transgenic Plants and Applications
- RNA Interference and Gene Delivery
- Blood Coagulation and Thrombosis Mechanisms
- Erythrocyte Function and Pathophysiology
- Drug Transport and Resistance Mechanisms
- Erythropoietin and Anemia Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Dialysis and Renal Disease Management
- Bacterial Infections and Vaccines
- Adenosine and Purinergic Signaling
- Acute Myeloid Leukemia Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Barrier Structure and Function Studies
- Chronic Myeloid Leukemia Treatments
- Apelin-related biomedical research
Newcastle University
2019-2025
University of Oxford
2024
Cardiff University
2006-2015
University of Wales
2003
The complement system is a key component of innate and adaptive immune responses. Complement regulation critical for prevention control disease. We have determined the crystal structure regulatory enzyme human factor I (fI). FI in proteolytically inactive form, demonstrating that it circulates zymogen-like state despite being fully processed to mature sequence. Mapping functional data from mutants fI onto suggests this form maintained by noncatalytic heavy-chain allosterically modulating...
A critical assessment of computational hit finding experiments (CACHE) challenge was conducted to predict ligands for the SARS-CoV-2 Nsp13 helicase RNA binding site, a highly conserved COVID-19 target. Twenty-three participating teams comprised chemists and data scientists used protein structure from fragment-screening paired with advanced machine learning methods each up 100 inhibitory ligands. Across all teams, 1957 compounds were predicted subsequently procured commercial catalogs...
A critical assessment of computational hit finding experiments (CACHE) challenge was conducted to predict ligands for the SARS-CoV-2 Nsp13 helicase RNA binding site, a highly conserved COVID-19 target. Twenty-three participating teams comprised chemists and data scientists used protein structure from fragment-screening paired with advanced machine learning methods each up 100 inhibitory ligands. Across all teams, 1957 compounds were predicted subsequently procured commercial catalogs...
A critical assessment of computational hit finding experiments (CACHE) challenge was conducted to predict ligands for the SARS-CoV-2 Nsp13 helicase RNA binding site, a highly conserved COVID-19 target. Twenty-three participating teams comprised chemists and data scientists used protein structure from fragment-screening paired with advanced machine learning methods each up 100 inhibitory ligands. Across all teams, 1957 compounds were predicted subsequently procured commercial catalogs...
Peritonitis and the rare sequela of encapsulating peritoneal sclerosis (EPS) are serious problems in patients on dialysis therapy. Chronic persistent injuries may be a risk factor EPS. We previously reported that chronic, proliferative peritonitis developed when zymosan was administered intraperitoneally following scraping injury rat peritoneum (Mizuno M, Ito Y, Hepburn N, Mizuno T, Noda Yuzawa Harris CL, Morgan BP, Matsuo S. J Immunol 183: 1403–1412, 2009). Peritoneal membrane complement...
Patients with genetically determined deficiency of complement component 5 are usually diagnosed because recurrent invasive Neisseria meningitidis infections. Approximately 40 individual cases have been worldwide. Nevertheless, reports the responsible genetic defects sporadic, and we know no previous C5 being associated a number independent meningococcal disease in particular communities. Here describe seven unrelated Western Cape, South African families. Three different mutations...
Introduction Complement-based drug discovery is undergoing a renaissance, empowered by new advances in structural biology, complement biology and development. Certain components of the pathway, particularly C1q C3, have been extensively studied context neurodegenerative disease, established as key therapeutic targets. C5 also has huge potential this arena, with its druggability clearly demonstrated success C5-inhibitor eculizumab.Areas covered We will discuss evidence supporting target along...
AbstractAs described in Chapter 1, the complement system comprises a battery of at least 20 components capable immediate response to foreign organism or cell, resulting lysis opsonization and phagocytosis. Uncontroled activation would result damage host tissues, extreme cases, consumption effective depletion components. Intrinsic cascade are multiple strategies for control, such as inherent lability enzymes, C3 C5 convertases, shortlived active/binding sites, binding site on C5b67 membranes....
The optimisation of a class AML differentiation agents is described to show improved potency, solubility and stability, reduced off target toxicity, tumour regression in murine model vivo .
<h3></h3> Despite a wealth of knowledge in the complexities complement cascade, and many decades endeavour, very few drugs have progressed to clinic. Recently, strong genetic associations with common diseases emerged fuelled fire drug discovery leading an explosion therapies development; while these agents others before them failed progress, their legacy is key future success. Obstacles successful development include target concentration turnover rates, ability appropriate site. The...