Nancy Gudgeon
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View article: mTOR activity and metabolic reprogramming of CD8+ T cells is impaired under hypoxia and within the multiple myeloma bone marrow
mTOR activity and metabolic reprogramming of CD8+ T cells is impaired under hypoxia and within the multiple myeloma bone marrow Open
Novel therapies for multiple myeloma (MM) aim to engage antitumor functions of T cells. However, evidence indicates these functions are limited within the bone marrow (BM) environment. This is relatively hypoxic in health, and studies indi…
View article: IL-7 promotes integrated glucose and amino acid sensing during homeostatic CD4+ T cell proliferation
IL-7 promotes integrated glucose and amino acid sensing during homeostatic CD4+ T cell proliferation Open
Interleukin (IL)-7 promotes T cell expansion during lymphopenia. We studied the metabolic basis in CD4+ T cells, observing increased glucose usage for nucleotide synthesis and oxidation in the tricarboxylic acid (TCA) cycle. Unlike other T…
View article: Cytoplasmic NAD/H synthesis via NRK1 controls CD4+ T cell ROS homeostasis, regulating inflammatory capacity and promoting survival
Cytoplasmic NAD/H synthesis via NRK1 controls CD4+ T cell ROS homeostasis, regulating inflammatory capacity and promoting survival Open
T cell metabolism increases upon activation, underpinning immune effector functions. Nicotinamide adenine dinucleotide (NAD/H) is an essential redox cofactor for glycolysis and mitochondrial substrate oxidation. It is also phosphorylated t…
View article: The glutamate/aspartate transporter EAAT1 is crucial for T-cell acute lymphoblastic leukemia proliferation and survival
The glutamate/aspartate transporter EAAT1 is crucial for T-cell acute lymphoblastic leukemia proliferation and survival Open
T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new thera…
View article: Iron deficiency causes aspartate-sensitive metabolic and proliferative dysfunction in CD8+ T cells
Iron deficiency causes aspartate-sensitive metabolic and proliferative dysfunction in CD8+ T cells Open
Summary Iron is an irreplaceable co-factor for metabolism. Iron deficiency affects >1 billion people, causing symptoms including anaemia and impaired immunity. Nevertheless, precisely how iron deprivation impacts immune cell function remai…
View article: Uptake of long-chain fatty acids from the bone marrow suppresses CD8+ T-cell metabolism and function in multiple myeloma
Uptake of long-chain fatty acids from the bone marrow suppresses CD8+ T-cell metabolism and function in multiple myeloma Open
T cells demonstrate impaired function in multiple myeloma (MM) but suppressive mechanisms in the bone marrow microenvironment remain poorly defined. We observe that bone marrow CD8+ T-cell function is decreased in MM compared with controls…
View article: Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity
Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity Open
Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-tra…
View article: <i>Salmonella</i>cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity
<i>Salmonella</i>cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity Open
Summary Bacterial cancer therapy (BCT) is a promising therapeutic for solid tumours. Salmonella enterica Typhimurium (STm) is well-studied amongst bacterial vectors due to advantages in genetic modification and metabolic adaptation. A long…
View article: Succinate uptake by T cells suppresses their effector function via inhibition of mitochondrial glucose oxidation
Succinate uptake by T cells suppresses their effector function via inhibition of mitochondrial glucose oxidation Open
Succinate dehydrogenase (SDH) loss-of-function mutations drive succinate accumulation in tumor microenvironments, for example in the neuroendocrine tumors pheochromocytoma (PC) and paraganglioma (PG). Control of innate immune cell activity…
View article: 1,25‐Dihydroxyvitamin D3 suppresses CD4<sup>+</sup> T‐cell effector functionality by inhibition of glycolysis
1,25‐Dihydroxyvitamin D3 suppresses CD4<sup>+</sup> T‐cell effector functionality by inhibition of glycolysis Open
In CD4 + T helper cells, the active form of vitamin D 3 , 1,25‐dihydroxyvitamin D 3 (1,25D) suppresses production of inflammatory cytokines, including interferon‐gamma (IFN‐γ), but the mechanisms for this are not yet fully defined. In inna…
View article: Control of T Cell Metabolism by Cytokines and Hormones
Control of T Cell Metabolism by Cytokines and Hormones Open
Dynamic, coordinated changes in metabolic pathway activity underpin the protective and inflammatory activity of T cells, through provision of energy and biosynthetic precursors for effector functions, as well as direct effects of metabolic…