J. H. Duncan Bassett
A5031268979- Thyroid Disorders and Treatments
- Bone Metabolism and Diseases
- Bone health and treatments
- Growth Hormone and Insulin-like Growth Factors
- Bone health and osteoporosis research
- Connective tissue disorders research
- RNA Research and Splicing
- Neuroendocrine Tumor Research Advances
- Osteoarthritis Treatment and Mechanisms
- Cytokine Signaling Pathways and Interactions
- Thyroid Cancer Diagnosis and Treatment
- Estrogen and related hormone effects
- Neuroblastoma Research and Treatments
- Bone fractures and treatments
- Fibroblast Growth Factor Research
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Inflammatory mediators and NSAID effects
- Pancreatic and Hepatic Oncology Research
- Neurogenetic and Muscular Disorders Research
- Pituitary Gland Disorders and Treatments
- Peptidase Inhibition and Analysis
- Genetic Associations and Epidemiology
- Parathyroid Disorders and Treatments
- Biomarkers in Disease Mechanisms
Imperial College London
2016-2025
Hammersmith Hospital
2010-2023
Imperial College Healthcare NHS Trust
2014-2018
Humboldt-Universität zu Berlin
2014
Medical Research Council
2002-2011
John Radcliffe Hospital
1991-1992
Addenbrooke's Hospital
1988
University of Cambridge
1988
Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that thought to undergo apoptosis once resorption is complete. Here, intravital imaging, we reveal RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted osteomorph accumulation. Single-cell RNA sequencing showed osteomorphs transcriptionally distinct...
Thyrotoxicosis is an important but under recognized cause of osteoporosis. Recently, TSH deficiency, rather than thyroid hormone excess, has been suggested as the underlying cause. To investigate molecular mechanism osteoporosis in disease, we characterized skeleton mice lacking either receptor alpha or beta (TRalpha(0/0), TRbeta-/-). Remarkably, presence normal circulating and concentrations, adult TRalpha(0/0) had osteosclerosis accompanied by reduced osteoclastic bone resorption, whereas...
Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses determined by local intracellular availability active hormone 3,5,3′-L-triiodothyronine (T3), which generated from T4 type 2 deiodinase enzyme (D2). To investigate role locally produced T3 in bone, we characterized mice deficient D2 (D2KO) serum level normal. Bones adult D2KO have reduced toughness brittle,...
Thyroid hormone (TH) and TH receptors (TRs) α β act by binding to response elements (TREs) in regulatory regions of target genes. This nuclear signaling is established as the canonical or type 1 pathway for action. Nevertheless, TRs also rapidly activate intracellular second-messenger pathways independently gene expression (noncanonical 3 TR signaling). To test physiological relevance noncanonical signaling, we generated knockin mice with a mutation DNA-binding domain that abrogates DNA...
Levothyroxine (LT4) is a form of thyroid hormone used to treat hypothyroidism. In the brain, T4 converted active T3 by type 2 deiodinase (D2). Thus, it intriguing that carriers Thr92Ala polymorphism in D2 gene (DIO2) exhibit clinical improvement when liothyronine (LT3) added LT4 therapy. Here, we report cargo protein ER Golgi intermediary compartment (ERGIC) vesicles, recycling between and Golgi. The Thr92-to-Ala substitution (Ala92-D2) caused stress activated unfolded response (UPR)....
Osteocytes are master regulators of the skeleton. We mapped transcriptome osteocytes from different skeletal sites, across age and sexes in mice to reveal genes molecular programs that control this complex cellular-network. define an osteocyte signature 1239 distinguishes other cells. 77% have no previously known role skeleton enriched for regulating neuronal network formation, suggesting programme is important communication. evaluated 19 parameters 733 knockout mouse lines 26 bone structure...
(Cell 184, 1330–1347.e1–e13; March 4, 2021) As a result of an author oversight in the originally published version this article, name author, Alexander Corr, did not appear list. This error has now been corrected article online, and contributions have updated accordingly to reflect Corr’s scRNA-seq analysis. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorptionMcDonald et al.CellFebruary 25, 2021In BriefTracking osteoclasts cycles fission fusion reveals...
Abstract Osteoarthritis causes pain and functional disability for over 500 million people worldwide. To develop disease-stratifying tools modifying therapies, we need a better understanding of the molecular basis disease in relevant tissue cell types. Here, study primary cartilage synovium from 115 patients with osteoarthritis to construct deep signature map disease. By integrating genetics transcriptomics proteomics, discover trait loci each type omics level, identify likely effector genes...
Childhood hypothyroidism delays ossification and bone mineralization, whereas adult thyrotoxicosis causes osteoporosis. To determine how effects of thyroid hormone (T3) during development manifest in bone, we characterized TRα1+/mβ+/− mice, which express a mutant T3 receptor (TR) α1 with dominant-negative properties due to reduced ligand-binding affinity. Remarkably, mice had osteosclerosis increased mineralization even though juveniles delayed ossification. This phenotype was partially...