A5051703859- Immune cells in cancer
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Chronic Lymphocytic Leukemia Research
- Mitochondrial Function and Pathology
- Cell Adhesion Molecules Research
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Acute Lymphoblastic Leukemia research
- Endoplasmic Reticulum Stress and Disease
- Acute Myeloid Leukemia Research
- Neuroblastoma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Sirtuins and Resveratrol in Medicine
- Adipose Tissue and Metabolism
- Lipid metabolism and biosynthesis
- Biochemical effects in animals
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Gastrointestinal disorders and treatments
- Parathyroid Disorders and Treatments
- T-cell and B-cell Immunology
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Iron Metabolism and Disorders
Harvard University
2018-2023
Boston VA Research Institute
2019-2023
National Institutes of Health
2019
Dana-Farber Cancer Institute
2019
National Institute of Allergy and Infectious Diseases
2019
Harvard University Press
2018
Gain-of-function mutations in isocitrate dehydrogenase (IDH) human cancers result the production of d-2-hydroxyglutarate (d-2HG), an oncometabolite that promotes tumorigenesis through epigenetic alterations. The cancer cell-intrinsic effects d-2HG are well understood, but its tumor cell-nonautonomous roles remain poorly explored. We compared with enantiomer, l-2HG, and found tumor-derived was taken up by CD8+ T cells altered their metabolism antitumor functions acute reversible fashion....
T cell stimulation is metabolically demanding. To exit quiescence, cells rely on environmental nutrients, including glucose and the amino acids glutamine, leucine, serine, arginine. The expression of transporters for these nutrients tightly regulated required activation. In contrast to acids, which are essential or require multi-step biosynthesis, alanine can be made from pyruvate by a single transamination. Here, we show that extracellular nevertheless efficient quiescence during naive...
Significance T cell-mediated immune responses are compromised in aged individuals, leading to increased morbidity and reduced response vaccination. Finding new ways boost cell immunity the elderly is key for enhancing their competence. In this work, we performed a systematic analysis of proteins metabolites young versus cells. Metabolic rewiring occurs cells following stimulation but dampened Moreover, show that functions can be enhanced by metabolite addition.
X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN) disease are caused by deficiency of the transporter 1 (MAGT1) gene. We studied 23 patients XMEN, 8 whom were naive. observed lymphadenopathy (LAD), cytopenias, liver disease, cavum septum pellucidum (CSP), increased CD4-CD8-B220-TCRαβ+ T cells (αβDNTs), in addition to previously described features an inverted CD4/CD8 ratio, CD4+ lymphocytopenia, B cells, dysgammaglobulinemia, decreased expression natural...
Magnesium transporter 1 (MAGT1) critically mediates magnesium homeostasis in eukaryotes and is highly-conserved across different evolutionary branches. In humans, loss–of–function mutations the MAGT1 gene cause X-linked deficiency with Epstein-Barr virus (EBV) infection neoplasia (XMEN), a disease that has broad range of clinical immunological consequences. We have previously shown EBV susceptibility XMEN associated defective expression antiviral natural-killer group 2 member D (NKG2D)...
Upon nutrient stimulation, pre-adipocytes undergo differentiation to transform into mature adipocytes capable of storing nutrients as fat. We profiled cellular metabolite consumption identify early metabolic drivers adipocyte differentiation. find that raises the uptake and numerous amino acids. In particular, branched-chain acid (BCAA) catabolism precedes promotes peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator adipogenesis. adipogenesis, mitochondrial sirtuin...
The tumor microenvironment (TME) is a unique metabolic niche that can inhibit CD8+ T cell metabolism and cytotoxic activity. It has been challenge to dissect the interplay between tumors cells. Consequently, mechanisms whereby TME regulates function are not completely understood. Here we establish an in vitro system recapitulates of allows us define cell-specific metabolism. We identify tumor-derived lactate as direct inhibitor cytotoxicity, revealing unexpected shunt tricarboxylic acid...