A5045175167- Erythrocyte Function and Pathophysiology
- Tryptophan and brain disorders
- Metabolomics and Mass Spectrometry Studies
- Diet and metabolism studies
- Blood transfusion and management
- Cancer, Hypoxia, and Metabolism
- Hemoglobinopathies and Related Disorders
- Acute Myeloid Leukemia Research
- Neonatal Health and Biochemistry
- Vitamin D Research Studies
- Blood groups and transfusion
- Epigenetics and DNA Methylation
- Adipose Tissue and Metabolism
- Immune cells in cancer
- Hemoglobin structure and function
- Histone Deacetylase Inhibitors Research
- Blood properties and coagulation
- Metabolism and Genetic Disorders
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Ferroptosis and cancer prognosis
- Renal cell carcinoma treatment
- Birth, Development, and Health
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Heme Oxygenase-1 and Carbon Monoxide
University of Colorado Anschutz Medical Campus
2016-2025
University of Colorado Denver
2016-2025
University of British Columbia
2023-2024
Indiana University Bloomington
2023-2024
The Medical Center of Aurora
2021-2024
Spanish National Cancer Research Centre
2024
Centro de Investigación del Cáncer
2024
Université de Bordeaux
2024
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2024
University of Pennsylvania
2024
BACKGROUND. Reprogramming of host metabolism supports viral pathogenesis by fueling proliferation, providing, for example, free amino acids and fatty as building blocks.
Significance The NLRP3 inflammasome is an intracellular oligomer regulating the activation of caspase-1 for processing and secretion IL-1β IL-18. Although there growing evidence to substantiate inhibition as a therapeutic option treatment inflammatory diseases, date, are no approved humans agents. OLT1177, β-sulfonyl nitrile molecule, shown be safe in humans, selective inhibitor inflammasome, with unique properties reverse metabolic costs inflammation treat IL-1β– IL-18–mediated diseases.
Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well relapse following initial response demonstrates the need for a deeper understanding mechanisms. In present study, we report that to venetoclax +azacitidine AML correlate closely developmental stage, where phenotypically primitive is sensitive, but monocytic more resistant. Mechanistically, resistant has distinct...
Abstract To study mechanisms underlying resistance to the BCL2 inhibitor venetoclax in acute myeloid leukemia (AML), we used a genome-wide CRISPR/Cas9 screen identify gene knockouts resulting drug resistance. We validated TP53, BAX, and PMAIP1 as genes whose inactivation results AML cell lines. Resistance resulted from an inability execute apoptosis driven by BAX loss, decreased expression of BCL2, and/or reliance on alternative family members such BCL2L1. The was accompanied changes...
The SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which primarily characterized by shortness breath, persistent dry cough, and fever. Because they transport oxygen, red blood cells (RBCs) may play a role in severity hypoxemia patients. present study combines state-of-the-art metabolomics, proteomics, lipidomics approaches to investigate impact on RBCs from 23 healthy subjects 29 molecularly diagnosed patients had increased levels glycolytic intermediates,...
The ability of a cancer cell to develop resistance anoikis, programmed death process triggered by substratum detachment, is critical step in the metastatic cascade. Triple-negative breast cancers (TNBC) exhibit higher rates metastasis after diagnosis, relative estrogen-positive cancers, but while TNBC cells are relatively more resistant mechanisms involved unclear. Through gene expression and metabolomic profiling forced suspension culture, we identified molecular pathway for...
Abstract Maternal obesity is associated with increased risk for offspring and non-alcoholic fatty liver disease (NAFLD), but the causal drivers of this association are unclear. Early colonization infant gut by microbes plays a critical role in establishing immunity metabolic function. Here, we compare germ-free mice colonized stool (MB) from 2-week-old infants born to obese (Inf-ObMB) or normal-weight (Inf-NWMB) mothers. Inf-ObMB-colonized demonstrate hepatic gene expression endoplasmic...
The implementation of mass spectrometry (MS)-based metabolomics is advancing many areas biomedical research. time associated with traditional chromatographic methods for resolving metabolites prior to analysis has limited the potential perform large-scale, highly powered studies and clinical applications.Here we describe a three-minute method rapid profiling central metabolic pathways through UHPLC/MS, tracing experiments in vitro vivo, targeted quantification compounds interest using spiked...
Background Results from recent, highly debated, retrospective studies raised concerns and prompted considerations about further testing the quality of long stored red blood cells a biochemical standpoint.Design Methods We performed an integrated mass spectrometry-based metabolomics proteomics time-course investigation on SAGM-stored cells. In parallel, structural changes during storage were monitored through scanning electron microscopy.Results detected increased levels glycolytic...
Pulmonary arterial hypertension (PAH) is characterized by abnormal growth and enhanced glycolysis of pulmonary artery endothelial cells. However, the mechanisms underlying alterations in energy production have not been identified.Here, we examined miRNA proteomic profiles blood outgrowth cells (BOECs) from patients with heritable PAH caused mutations bone morphogenetic protein receptor type 2 (BMPR2) gene idiopathic to determine glycolysis. We hypothesized that BOECs PAH, downregulation...
MDM2 and MDMX, negative regulators of the tumor suppressor p53, can work separately as a heteromeric complex to restrain p53's functions. also has pro-oncogenic roles in cells, tissues, animals that are independent p53. There is less information available about p53-independent MDMX or MDM2–MDMX complex. We found facilitate ferroptosis cells with without Using small molecules, RNA interference reagents, mutant forms we likely working part complex, normally ferroptotic death. observed alter...
Background: An emerging metabolic theory of pulmonary hypertension (PH) suggests that cellular and mitochondrial dysfunction underlies the pathology this disease. We others have previously demonstrated existence hyperproliferative, apoptosis-resistant, proinflammatory adventitial fibroblasts from human bovine hypertensive arterial walls (PH-Fibs) exhibit constitutive reprogramming glycolytic metabolism, accompanied by an increased ratio glucose catabolism through glycolysis versus...
Numerous studies demonstrate that neuroinflammation is a key player in the progression of Alzheimer's disease (AD). Interleukin (IL)-1β main inducer inflammation and therefore prime target for therapeutic options. The inactive IL-1β precursor requires processing by nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome into mature active form. Studies have shown up-regulated brains patients with AD, genetic inactivation NLRP3 improves...
Over 5 million people around the world have tested positive for beta coronavirus SARS-CoV-2 as of May 29, 2020, a third which are in United States alone. These infections associated with development disease known COVID-19, is characterized by several symptoms, including persistent dry cough, shortness breath, chills, muscle pain, headache, loss taste or smell, and gastrointestinal distress. COVID-19 has been elevated mortality (over 100 thousand already died US alone), mostly due to...
Abstract Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that S1P levels rapidly increase 21 healthy lowland volunteers at 5,260 m altitude on day 1 and continue increasing 16 days concurrently elevated sphingonisne kinase (Sphk1) activity haemoglobin (Hb) oxygen (O 2 ) release capacity. Mouse genetic...