David O’Sullivan
A5049647320- Immune Cell Function and Interaction
- Immune cells in cancer
- T-cell and B-cell Immunology
- Cancer, Hypoxia, and Metabolism
- Sphingolipid Metabolism and Signaling
- Peroxisome Proliferator-Activated Receptors
- CAR-T cell therapy research
- Diabetes and associated disorders
- Multiple Sclerosis Research Studies
- Pancreatic function and diabetes
- Mitochondrial Function and Pathology
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- Genomics, phytochemicals, and oxidative stress
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Hematopoietic Stem Cell Transplantation
- Cancer Treatment and Pharmacology
- Adipose Tissue and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Acute Myeloid Leukemia Research
- Phagocytosis and Immune Regulation
- Epigenetics and DNA Methylation
- Cytomegalovirus and herpesvirus research
- Microtubule and mitosis dynamics
Malaghan Institute of Medical Research
2021-2025
Max Planck Institute of Immunobiology and Epigenetics
2016-2023
Washington University in St. Louis
2013-2015
Victoria University of Wellington
2009-2014
University of Cambridge
1993
Albany Medical Center Hospital
1990
A characteristic of memory T (T M ) cells is their ability to mount faster and stronger responses reinfection than naïve N do in response an initial infection. However, the mechanisms that allow this rapid recall are not completely understood. We found CD8 have more mitochondrial mass and, upon activation, resulting secondary effector E proliferate quickly, produce cytokines, maintain greater ATP levels primary cells. also after increase oxidative phosphorylation aerobic glycolysis sustain a...
How cells adapt metabolism to meet demands is an active area of interest across biology. Among a broad range functions, the polyamine spermidine needed hypusinate translation factor eukaryotic initiation 5A (eIF5A). We show here that hypusinated eIF5A (eIF5AH) promotes efficient expression subset mitochondrial proteins involved in TCA cycle and oxidative phosphorylation (OXPHOS). Several these have targeting sequences (MTSs) part confer increased dependency on eIF5AH. In macrophages,...
Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation the surrounding microenvironment is therefore key maintaining appropriate cell function. For instance, cancer use acetate as a substrate alternative fuel metabolism growth. Here, we show that rescues effector function in glucose-restricted CD8+ cells. Mechanistically, promotes histone acetylation chromatin accessibility enhances IFN-γ gene...
Oncogenic JAK mutation sensitizes myeloproliferative neoplasms to immune checkpoint inhibition.
Phorbol esters have been reported to decrease sensitivity or responsiveness insulin in cells vitro. Since phorbol are analogues of endogenously produced 1,2-diacylglycerol, the present study investigated whether 1,2-diacylglycerol concentration is elevated insulin-resistant tissues rat vivo. Studies were done on 11-12-week-old genetically obese Zucker rats, which insulin-resistant. Lean rats served as controls. Levels increased 82% liver, 136% calf muscles, 72% soleus muscle, a slow-twitch...
Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has a dismal prognosis. We found that T cells of patients relapsing with AML allo-HCT exhibited reduced glycolysis and interferon-γ production. Functional studies in multiple mouse models showed leukemia-derived lactic acid (LA) interfered proliferation. Mechanistically, LA intracellular pH cells, led to lower transcription glycolysis-related enzymes, decreased activity essential metabolic...
Significance Fever is a common symptom of infections and inflammation. We observed CD8 + T cells exposed to febrile-range temperature during activation, augmented mitochondrial mass, metabolic activity. An adoptive transfer these into tumor-bearing mice led enhanced antitumor responses, suggesting that exposure febrile activation contributes the development robust cell responses. identified translation integral mass function temperature. Collectively, this research raises possibility fever...
Mitochondria constantly adapt to the metabolic needs of a cell. This mitochondrial plasticity is critical T cells, which modulate metabolism depending on antigen-driven signals and environment. We show here that de novo synthesis membrane-specific lipid cardiolipin maintains CD8+ cell function. cells deficient for cardiolipin-synthesizing enzyme PTPMT1 had reduced responded poorly antigen because basal levels were required activation. However, neither synthesis, nor its Tafazzin-dependent...
Modification of the innate immune cell environment has recently been recognized as a viable treatment strategy for reducing autoimmune disease pathology. MIS416 is microparticulate response modifier that targets myeloid cells, activating cytosolic receptors NOD2 and TLR9, completed phase 1b/2a trial secondary progressive multiple sclerosis. Using mouse model sclerosis, we are investigating pathways by which activation TLR9 may modify subsequent T cell-mediated responses. We have found...