A5028543132- Cancer, Hypoxia, and Metabolism
- Vitamin C and Antioxidants Research
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Metabolomics and Mass Spectrometry Studies
- Metabolism, Diabetes, and Cancer
- Erythrocyte Function and Pathophysiology
- COVID-19 Clinical Research Studies
- Hemoglobinopathies and Related Disorders
- Parasites and Host Interactions
- Melanoma and MAPK Pathways
- Parasite Biology and Host Interactions
- Mitochondrial Function and Pathology
- Neuroblastoma Research and Treatments
- Sepsis Diagnosis and Treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Folate and B Vitamins Research
- Helminth infection and control
- Immune responses and vaccinations
- Immune cells in cancer
- Venous Thromboembolism Diagnosis and Management
The University of Texas Southwestern Medical Center
2015-2025
Children's Medical Center
2014-2025
Southwestern Medical Center
2014-2023
University of Cambridge
2010-2014
Howard Hughes Medical Institute
2014
Little is known about the metabolic regulation of rare cell populations because most metabolites are hard to detect in small numbers cells. We previously described a method for metabolomic profiling flow cytometrically isolated hematopoietic stem cells (HSCs) that detects 60 10,000 (Agathocleous et al., 2017). Here we describe new involving hydrophilic liquid interaction chromatography and high-sensitivity orbitrap mass spectrometry detected 160 HSCs, including many more glycolytic lipid...
Severe COVID-19 is characterized by an increase in the number and changes function of innate immune cells including neutrophils. However, it not known how metabolome patients with COVID-19. To address these questions, we analyzed neutrophils from severe or mild healthy controls. We identified widespread dysregulation neutrophil metabolism disease progression amino acid, redox, central carbon metabolism. Metabolic were consistent reduced activity glycolytic enzyme GAPDH. Inhibition GAPDH...
Targeting the dependency of MLL-rearranged (MLLr) leukemias on menin with small molecule inhibitors has opened new therapeutic strategies for these poor-prognosis diseases. However, rapid development inhibitor resistance calls combinatory to improve responses and prevent resistance. Here we show that leukemia stem cells (LSCs) MLLr acute myeloid (AML) exhibit enhanced guanine nucleotide biosynthesis, inhibition which leads differentiation sensitization inhibitors. Mechanistically, targeting...
Alpha-ketoglutarate (α-KG) is required for chromatin demethylation but mechanisms controlling α-KG abundance in the nucleus are poorly defined. Therefore, we designed a biosensor system to monitor this metabolite pool human cells using an α-KG-responsive cyanobacterial transcription factor, NtcA. We then coupled with genetic screen identify genes that regulate nucleus, defining inter-organelle pathway which sequential mitochondrial activities of GPT2 transaminase and SLC25A11 transporter...
In many growing tissues, slowly dividing stem cells give rise to rapidly proliferating progenitors that eventually exit the cell cycle and differentiate. Growth rates are limited by nutrient availability, but it is unclear which steps of proliferation-differentiation programme particularly sensitive fuel supplies. We examined how deprivation (ND) affects progenitor in ciliary marginal zone (CMZ) amphibian retina, a well-characterised neurogenic niche. show ND specifically blocks...
Abstract Helminth infections are common in animals. However, the impact of a helminth infection on function hematopoietic stem cells (HSCs) and other has not been comprehensively defined. In this article, we describe response to mice with Schistosoma mansoni, parasitic flatworm that causes schistosomiasis. We analyzed frequency or number cell types bone marrow, spleen, liver, thymus, blood observed multiple changes caused by infection. Schistosome impaired marrow HSC after serial...
Abstract Solid cancer cells commonly enter the blood and disseminate systemically but are highly inefficient at forming distant metastases for poorly understood reasons. We studied human melanomas that differed in their metastasis histories patients capacity to metastasize NSG mice. All had high frequencies of formed subcutaneous tumors, much lower percentages tumors after intravenous or intrasplenic transplantation, particularly among metastasizers. Melanoma visceral organs experienced...
Helminth infections are common in animals. However, the impact of a helminth infection on function hematopoietic stem cells (HSCs) and other has not been comprehensively defined. Here we describe response to mice with
Background About 90% of mortality associated with cancer is attributable to metastatic disease. Thus, our ability treat largely dependent on the capacity prevent metastasis. Metabolic reprogramming recognized support cellular transformation and tumor initiation; however, whether or how metabolism supports metastasis remains an open question. This study seeks identify metabolic predictors metastasis, rationale that understanding changes will lead novel insights into perhaps new therapies...
Background A general problem in biology is whether different types of cells the same tissue are metabolically from each other, and such differences important for cellular function. Experiments that can comprehensively measure metabolome typically require millions cultured cannot be used with small numbers rare freshly isolated tissues. In particular, hematopoietic stem (HSCs), blood forming bone marrow, have been intensively studied decades but their metabolic composition largely unknown....
Little is known about the metabolic regulation of rare cell populations because most metabolites are hard to detect in small numbers cells. We previously described a method for metabolomic profiling flow cytometrically-isolated hematopoietic stem cells (HSCs) that detects approximately 60 10,000 (Agathocleous et al., 2017). Here we describe new involving hydrophilic liquid interaction chromatography (HILIC) and high-sensitivity orbitrap mass spectrometry detected 160 HSCs, including many...