A5061657273- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Hippo pathway signaling and YAP/TAZ
- Gene Regulatory Network Analysis
- Cancer, Hypoxia, and Metabolism
- Genomics and Chromatin Dynamics
- PI3K/AKT/mTOR signaling in cancer
- Mast cells and histamine
- Acute Myeloid Leukemia Research
- Phagocytosis and Immune Regulation
- Diabetes and associated disorders
- Histone Deacetylase Inhibitors Research
- Virus-based gene therapy research
- Heat shock proteins research
- Cancer Immunotherapy and Biomarkers
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
St. Jude Children's Research Hospital
2017-2025
University of Helsinki
2015
Abstract Cancer cells evade T cell-mediated killing through tumour–immune interactions whose mechanisms are not well understood 1,2 . Dendritic (DCs), especially type-1 conventional DCs (cDC1s), mediate cell priming and therapeutic efficacy against tumours 3 DC functions orchestrated by pattern recognition receptors 3–5 , although other signals involved remain incompletely defined. Nutrients emerging mediators of adaptive immunity 6–8 but whether nutrients affect function or communication...
Abstract Regulatory T (T reg ) cells derived from the thymus (tT and periphery (pT have central distinct functions in immunosuppression, but mechanisms for generation activation of subsets vivo are unclear. Here, we show that mechanistic target rapamycin (mTOR) unexpectedly supports homeostasis functional tT pT cells. mTOR signaling is crucial programming activated -cell function to protect immune tolerance tissue homeostasis. -specific deletion drives spontaneous effector T-cell...
c-Myc coordinates context-dependent homeostasis and transitional activation with metabolic programming of regulatory T cells.
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for cell survival and demonstrate direct relationship between , elevated OxPhos gene expression, acquired chemoresistance pre-leukemic leukemic models. Disrupting with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction...
Development of αβ and γδ T cells requires coupling environmental signals with metabolic redox regulation by mTORC1.
Many signaling and other genes known as "hidden" drivers may not be genetically or epigenetically altered differentially expressed at the mRNA protein levels, but, rather, drive a phenotype such tumorigenesis via post-translational modification mechanisms. However, conventional approaches based on genomics differential expression are limited in exposing hidden drivers. Here, we present comprehensive algorithm toolkit NetBID2 (data-driven network-based Bayesian inference of drivers, version...
Background and Aims: Hexokinases (HKs), a group of enzymes catalyzing the first step glycolysis, have been shown to play important roles in liver metabolism tumorigenesis. Our recent studies identified HKDC1 as top candidate associated with cancer metastasis. We aimed compare its cell type specificity other HKs upregulated investigate molecular mechanisms underlying involvement Approach Results: found that, compared HK1 HK2, two commonly cancer, was most strongly metastasis potential tumors...
Myelopoiesis is necessary for the generation of mature myeloid cells during homeostatic turnover and immunological insults; however, metabolic requirements this process remain poorly defined. Here, we demonstrate that myelopoiesis, including monocyte macrophage differentiation, requires mechanistic target rapamycin complex 1 (mTORC1) signaling anabolic metabolism. Loss mTORC1 impaired myelopoiesis under steady state dampened innate immune responses against Listeria monocytogenes infection....
PTEN-PI3K and IL-7R–mTORC1–Myc are two discrete signaling axes driving B cell development.
Abstract Chimeric antigen receptor (CAR)-T cell therapies, while promising for CD19+ hematological malignancies, often face setbacks due to relapses. Our research identifies GPR65 as a tumor-specific determinant affecting the efficacy of CAR-T therapy. In human patients and an immune-competent mouse model B-cell acute lymphoblastic leukemia (B-ALL), low expression correlates with resistance treatment. knockout (GPR65 KO) tumors in mice similarly exhibit resistance. Through single-cell...
HSPB1 belongs to the family of small heat shock proteins (sHSP) that have importance in protection against unfolded protein stress, cancer cells for escaping drug toxicity stress and neurons suppression aggregates. sHSPs a conserved α-crystalline domain (ACD), flanked by variable N- C-termini, whose functions are not fully understood. Dominant missense variants HSPB1, locating mostly ACD, been linked inherited neuropathy.Patients underwent detailed clinical neurophysiologic characterization....