- Hip disorders and treatments
- Orthopaedic implants and arthroplasty
- Acute Myeloid Leukemia Research
- Total Knee Arthroplasty Outcomes
- Osteoarthritis Treatment and Mechanisms
- Microtubule and mitosis dynamics
- Nuclear Structure and Function
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Bone and Joint Diseases
- Pelvic and Acetabular Injuries
- Virus-based gene therapy research
- Hip and Femur Fractures
- Protein Degradation and Inhibitors
- Orthopedic Infections and Treatments
- Shoulder Injury and Treatment
- interferon and immune responses
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Hematopoietic Stem Cell Transplantation
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Cancer-related molecular mechanisms research
Princess Margaret Cancer Centre
2018-2024
University Health Network
2018-2024
Keele University
2022
Versus Arthritis
2022
Health Net
2020
Indian Institute of Science Education and Research Thiruvananthapuram
2014-2017
University of Oxford
2006-2016
Nuffield Orthopaedic Centre
2009-2016
Indian Institute of Science Bangalore
2014
NIHR Oxford Musculoskeletal Biomedical Research Centre
2014
Abstract Mitochondrial metabolites regulate leukaemic and normal stem cells by affecting epigenetic marks. How mitochondrial enzymes localize to the nucleus control cell function is less understood. We discovered that metabolic enzyme hexokinase 2 (HK2) localizes in haematopoietic cells. Overexpression of nuclear HK2 increases properties decreases differentiation, whereas selective knockdown promotes differentiation function. Nuclear localization phosphorylation-dependent, requires active...
Introduction Hip arthroscopy is increasingly adopted for the treatment of intra-articular and extra-articular pathologies. Studies from USA demonstrate a 365% increase in number procedures performed between 2004 2009 250% 2007 2011. There limited evidence long-term efficacy this procedure hip not universally funded across England. The aim study to describe temporal trends adoption England 2002 2013 forecast next 10 years. Methods A search Hospital Episodes Database was all codes describing...
We assessed the orientation of acetabular component in 1070 primary total hip arthroplasties with hard-on-soft, small diameter bearings, aiming to determine size and site target zone that optimises outcome. Outcome measures included complications, dislocations, revisions ΔOHS (the difference between Oxford Hip Scores pre-operatively five years post-operatively). A wide scatter was observed (2sd 15°). Placing within Lewinnek’s not associated withimproved Of different sizes tested (± 5°, ± 10°...
TAK-243 is a first-in-class inhibitor of ubiquitin-like modifier activating enzyme 1 that catalyzes ubiquitin activation, the first step in ubiquitylation cascade. Based on its preclinical efficacy and tolerability, has been advanced to phase I clinical trials malignancies. Nonetheless, determinants sensitivity remain largely unknown. Here, we conducted genome-wide CRISPR/Cas9 knockout screen acute myeloid leukemia (AML) cells presence identify genes essential for action. We identified BEN...
Kinetochore couples chromosome movement to dynamic microtubules, a process that is fundamental mitosis in all eukaryotes but poorly understood. In vertebrates, spindle-kinetochore-associated (Ska1-3) protein complex plays an important role this process. However, the proteins stabilize Ska-mediated kinetochore-microtubule attachment remain unknown. Here we show microtubule plus-end tracking EB1 facilitates Ska localization on microtubules vertebrate cells. depletion results significant...
Objectives The number of surgical procedures performed each year to treat femoroacetabular impingement (FAI) continues rise. Although there is evidence that surgery can improve symptoms in the short-term, no it slows development osteoarthritis (OA). We a feasibility study determine whether patient and surgeon opinion was permissive for Randomised Controlled Trial (RCT) comparing operative with non-operative treatment FAI. Methods Surgeon obtained using validated questionnaires at Specialist...
To review patients with proximal femoral nails (PFNs) in our hospital that developed complications and needed revision.Between January 2000 June 2006, records of 216 PFN fixations for traumatic extracapsular trochanteric fractures (n=160), pathological (n=23), as a prophylactic measure metastasis (n=33) were retrospectively reviewed. The injury mechanism, reduction technique quality, time to cause implant failure recorded.12 PFNs failed: 8 the trauma group, 3 one nailing group. Two broke at...
Microtubule plus‑end‑binding protein (+TIP) EB1 has been shown to be upregulated in breast cancer cells and promote tumor growth vivo. However, its effect on the cellular actions of microtubule‑targeted drugs remained poorly understood. By using biochemical assays, we demonstrate that plays a critical role regulating sensitivity anti‑microtubule drug, paclitaxel (PTX). Cell viability assays revealed expression cell lines correlated with reduction their PTX. Knockdown by...
ObjectivesTo describe and compare trends in the frequency of opioid prescribing/dispensing English Swedish patients with osteoarthritis prior to total knee replacement (TKR).Methods49,043 from an national database (Clinical Practice Research Datalink) 5,955 Skåne Healthcare register undergoing TKR between 2015 2019 were included, alongside 1:1 age-, sex-, practice (residential area) matched controls. Annual prevalence rates ratio (PRR) (any, by strength) 10 years (or index date for controls)...
AML cells are arranged in a hierarchy with stem/progenitor giving rise to more differentiated bulk cells. Despite the importance of stem/progenitors pathogenesis AML, determinants state not fully understood. Through comparison genes that significant for growth and viability by way CRISPR screen, differentially expressed leukemia stem (LSC), we identified importin 11 (IPO11) as novel target AML. Importin is member β family proteins mediate transport across nuclear membrane. In knockdown IPO11...
This study aimed to define the role of lateral X-ray in assessment and treatment planning proximal femoral fractures. Occult fractures were not included.Radiographs from 359 consecutive patients with admitted our emergency department over a 12 month period divided into anteroposterior (AP) views views. Three blinded reviewers independently assessed radiographs, first AP alone then plus views, noting fracture classification for each radiograph. These assessments compared intra-operative...
Early-stage treatments for osteoarthritis are attracting considerable interest as a means to delay, or avoid altogether, the pain and lack of mobility associated with late-stage disease, burden that it places on community. With development these comes need assess tissue which they applied, both in trialling new an aid clinical decision making. Here, we measure range mechanical indentation, ultrasound near-infrared spectroscopy parameters normal osteoarthritic bovine joints vitro describe...
Centrioles are essential components of the animal centrosome and play crucial roles in formation cilia flagella. They cylindrical structures composed nine triplet microtubules organized around a central cartwheel. Recent studies have identified spindle assembly abnormal protein SAS-6 as critical component necessary for However, molecular details how cartwheel participates centriolar microtubule not been clearly understood. In this report, we show that C-terminal tail (residues 470-657) human...