A5039807252- PI3K/AKT/mTOR signaling in cancer
- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Lipid Membrane Structure and Behavior
- Phagocytosis and Immune Regulation
- Inhalation and Respiratory Drug Delivery
- Metabolism, Diabetes, and Cancer
- Blood disorders and treatments
- Protein Tyrosine Phosphatases
- Pneumocystis jirovecii pneumonia detection and treatment
- Immunodeficiency and Autoimmune Disorders
- Pharmaceutical studies and practices
- Photoreceptor and optogenetics research
- Erythrocyte Function and Pathophysiology
- Retinal Development and Disorders
- Lung Cancer Treatments and Mutations
- Zebrafish Biomedical Research Applications
- Lysosomal Storage Disorders Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Chronic Lymphocytic Leukemia Research
- Pancreatic function and diabetes
- Lipid metabolism and biosynthesis
- Cystic Fibrosis Research Advances
- Neuroscience and Neuropharmacology Research
Babraham Institute
2014-2023
GlaxoSmithKline (India)
2019
GlaxoSmithKline (United Kingdom)
2019
Hammersmith Medicines Research
2019
Babraham Bioscience Technologies (United Kingdom)
2013-2014
École Polytechnique Fédérale de Lausanne
2012
Answers from Exomes Exome sequencing, which targets only the protein-coding regions of genome, has potential to identify underlying genetic causes rare inherited diseases. Angulo et al. (p. 866 , published online 17 October; see Perspective by Conley and Fruman ) performed exome sequencing individuals seven unrelated families with severe, recurrent respiratory infections. The patients carried same mutation in gene coding for catalytic subunit phosphoinositide 3-kinase δ (PI3Kδ). caused...
The PI3K signaling pathway regulates cell growth and movement is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, latter producing PI(3,4)P2. PTEN tumor suppressor thought to function primarily as a 3-phosphatase, limiting activation of this pathway. Here we show that also functions PI(3,4)P2 both vitro vivo. major phosphatase Mcf10a cytosol, loss INPP4B, known 4-phosphatase, leads synergistic...
We report the semisynthesis of a fluorescent glutamate sensor protein on cell surfaces. Sensor excitation at 547 nm yields glutamate-dependent emission spectrum between 550 and 700 that can be exploited for ratiometric sensing. On cells, displays change 1.56. The high sensitivity toward concentration changes its exclusive extracellular localization make it an attractive tool sensing in neurobiology.
We disrupted the gene encoding lysophosphatidylinositol-acyltransferase-1 (LPIAT1) in mouse with aim of understanding its role determining cellular phosphoinositide content. LPIAT1−/− mice were born at lower than Mendelian ratios and exhibited a severe developmental brain defect. compared phospholipid content livers brains from LPIAT1+/+ littermates by LC-ESI/MS. In accord previous studies, most abundant molecular species each class (PtdIns, PtdInsP, PtdInsP2 PtdInsP3) possessed C38∶4...
Abstract Cell migration is controlled by PI3Ks, which generate lipid messengers phosphatidylinositol-3,4,5-trisphosphate and phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] consequently recruit pleckstrin homology (PH) domain–containing signaling proteins. PI3K inhibition impairs of normal transformed B cells, an effect thought to partly underlie the therapeutic efficacy inhibitors in treatment cell malignancies such as chronic lymphocytic leukemia. Although a number studies have...
Nemiralisib (GSK2269557), a potent inhaled inhibitor of phosphoinositide 3-kinase <i>δ</i> (PI3K<i>δ</i>), is being developed for the treatment respiratory disorders including chronic obstructive pulmonary disease. Determining pharmacokinetic (PK) and pharmacodynamic (PD) responses drugs early during drug development key to informing appropriate dose preferred regimen in patients. We set out measure PD changes induced sputum combination with concentrations plasma bronchoalveolar lavage (BAL)...
The PIP3/PI3K network is a central regulator of metabolism and frequently activated in cancer, commonly by loss the PIP3/PI(3,4)P2 phosphatase, PTEN. Despite huge research investment, drivers PI3K normal tissues how they adapt to overactivation are unclear. We find that healthy mouse prostate activity driven RTK/IRS signaling constrained pathway feedback. In absence PTEN, dramatically remodeled. A poorly understood YXXM- PIP3/PI(3,4)P2-binding PH domain-containing adaptor, PLEKHS1, became...
Summary The PIP 3 /PI3K network is a central regulator of metabolism and frequently activated in cancer, commonly by loss the /PI(3,4)P 2 -phosphatase, PTEN. Despite huge investment, drivers PI3K normal tissues how they adapt to overactivation are unclear. We find that healthy mouse prostate activity driven RTK/IRS signalling constrained pathway-feedback. In absence PTEN, dramatically remodelled. A poorly understood, YXXM -binding PH domain-containing, adaptor, PLEKHS1, became dominant...