A5049419220- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Vascular Malformations and Hemangiomas
- Pharmacology and Obesity Treatment
- Diet and metabolism studies
- Liver Disease Diagnosis and Treatment
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- PI3K/AKT/mTOR signaling in cancer
- Diabetes Management and Research
- Vascular Malformations Diagnosis and Treatment
- Genetic and Kidney Cyst Diseases
- Pancreatic function and diabetes
- Liver Disease and Transplantation
- Artificial Intelligence in Healthcare
- Genetic and rare skin diseases.
- Urological Disorders and Treatments
- Plant nutrient uptake and metabolism
- Tumors and Oncological Cases
- Neurofibromatosis and Schwannoma Cases
- Electrolyte and hormonal disorders
- Tuberous Sclerosis Complex Research
- Lipid metabolism and disorders
- Retinal Imaging and Analysis
- Genetic Syndromes and Imprinting
- Hedgehog Signaling Pathway Studies
AstraZeneca (United Kingdom)
2020-2025
University of Central Florida
2025
University of Cambridge
2012-2021
NIHR Cambridge Biomedical Research Centre
2015-2021
Wellcome/MRC Institute of Metabolic Science
2016-2021
National Institute for Health Research
2018-2021
Wellcome Trust
2015-2018
Addenbrooke's Hospital
2015-2017
MRC Epidemiology Unit
2017
Southern General Hospital
2014
Somatic activating mutations in the phosphatidylinositol‐3‐kinase/AKT/mTOR pathway underlie heterogeneous segmental overgrowth phenotypes. Because of extreme differences among patients, we sought to characterize phenotypic spectrum associated with different genotypes and mutation burdens, including a better understanding complications natural history. Historically, clinical diagnoses patients PIK3CA have included Fibroadipose hyperplasia or Overgrowth (FAO), Hemihyperplasia Multiple...
Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous (AVM).To investigate the pathogenesis sporadic intracranial extracranial VMs in 160 children which known genetic causes had been excluded, we sequenced DNA from affected tissue optimized...
Mutant Pik3ca gives rise to venous malformations.
Abstract By moving essential body fluids and molecules, motile cilia flagella govern respiratory mucociliary clearance, laterality determination the transport of gametes cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly dynein arm motors into axonemes. Before their import flagella, multi-subunit axonemal arms are thought to be stabilized pre-assembled in cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin HSP90...
PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric caused mosaic activating PIK3CA variants. encodes the p110α catalytic subunit phosphatidylinositol-3-kinase (PI3K), critical transducer growth factor signaling. As mTOR mediates growth-promoting actions PI3K, we hypothesized that inhibitor sirolimus would slow pathological overgrowth. Thirty-nine participants with PROS and progressive were enrolled into open-label studies across...
To assess the efficacy, safety and tolerability of cotadutide in patients with type 2 diabetes mellitus chronic kidney disease.In this phase 2a study (NCT03550378), body mass index 25-45 kg/m2 , estimated glomerular filtration rate 30-59 ml/min/1.73 m2 [glycated haemoglobin 6.5-10.5% (48-91 mmol/mol)] controlled insulin and/or oral therapy combination, were randomized 1:1 to once-daily subcutaneous (50-300 μg) or placebo for 32 days. The primary endpoint was plasma glucose concentration...
Abstract Cotadutide is a dual glucagon-like peptide 1 and glucagon receptor agonist under development for the treatment of non-alcoholic steatohepatitis type 2 diabetes mellitus (T2DM) chronic kidney disease. Non-alcoholic complex disease with no approved pharmacotherapies, arising from an underlying state systemic metabolic dysfunction in association T2DM obesity. has been shown to improve glycaemic control, body weight, lipids, liver fat, inflammation fibrosis. We conducted two-part,...
Abstract Mutations in PIK3CA are very frequent cancer and lead to sustained PI3K pathway activation. The impact of acute expression mutant during early stages malignancy is unknown. Using a mouse model activate the Pik3ca H1047R hotspot mutation heterozygous state from its endogenous locus, we here report that induces centrosome amplification cultured cells (through involving AKT, ROCK CDK2/Cyclin E-nucleophosmin) tissues, increased vitro cellular tolerance spontaneous genome doubling. We...
Abstract Aims To establish which components of energy balance mediate the clinically significant weight loss demonstrated with use cotadutide, a glucagon‐like peptide‐1 (GLP‐1)/glucagon receptor dual agonist, in early‐phase studies. Materials and Methods We conducted phase 2a, single‐centre, randomized, placebo‐controlled trial overweight obese adults type 2 diabetes. Following 16‐day single‐blind placebo run‐in, participants were randomized 2:1 to double‐blind 42‐day subcutaneous treatment...
Hypertension and diabetes mellitus (DM) are major causes of morbidity mortality, with growing burdens in low-income countries where they underdiagnosed undertreated. Advances machine learning may provide opportunities to enhance diagnostics settings limited medical infrastructure.
PurposeHypomelanosis of Ito (HI) is a skin marker somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary phenotype and clinical spectrum neurodevelopmental manifestations MTOR-related HI.MethodsFrom two cohorts totaling 71 patients mosaicism, we identified 14 Blaschko-linear one flag-like pigmentation abnormalities, psychomotor impairment or seizures, postzygotic variant skin. Patient records, including...
Abstract Cotadutide is a dual glucagon‐like peptide‐1 (GLP‐1)/glucagon receptor agonist. Gastrointestinal adverse effects are known to be associated with GLP‐1 agonism and can mitigated through tolerance development via gradual up‐titration. This analysis aimed characterize the relationship between exposure nausea incidence optimize titration schemes. The model was developed pooled data from cotadutide‐administrated studies. Three different modeling approaches, proportional odds (PO),...
The authors have identified a fourth flagellin gene in 21850 bp region of the Agrobacterium tumefaciens C58C1 chromosome containing at least 20 genes concerned with flagellar structure, assembly and function. Three genes, flaA, flaB flaC, orientated rightward, are positioned tandem array right end, fourth, substantially larger gene, flaD, opposite orientation, left end. Between these lie four apparent operons, two transcribed each direction (motA, flhB leftward; flgF, flgB rightward) from...
PurposePIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety this population. Our aim was to establish six-month tolerability of low-dose taselisib, selective class I PI3K inhibitor, PROS patients.MethodsPatients over 16 years with PIK3CA were included phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day then 24...
Zibotentan, a selective endothelin A receptor antagonist, is in development for chronic liver and kidney disease. The pharmacokinetics (PK) of zibotentan were previously investigated patients with either renal impairment or hepatic impairment, but the impact both pathologies on PK was not evaluated. This study evaluated tolerability single oral dose participants concurrent moderate versus control participants.
Background and Aims: Cotadutide, a dual receptor agonist with glucagon-like peptide-1 (GLP-1) glucagon activity, is being researched for the potential treatment of nonalcoholic steatohepatitis. Given known effects on hepatic glycogen lipid metabolism, aim this phase 2a study was to investigate effect cotadutide glycogen. Methods: In double-blind, placebo-controlled study, 21 overweight or obese adults type 2 diabetes mellitus (HbA1c ≤ 8%) were randomized receive once-daily subcutaneous (n =...