A5066414145- Cancer, Hypoxia, and Metabolism
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Air Quality and Health Impacts
- Neonatal Respiratory Health Research
- Mitochondrial Function and Pathology
- Immune cells in cancer
- Pulmonary Hypertension Research and Treatments
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Medical Imaging and Pathology Studies
- Fibroblast Growth Factor Research
- Pancreatic function and diabetes
- Obstructive Sleep Apnea Research
- Endoplasmic Reticulum Stress and Disease
- Neuroscience of respiration and sleep
- Liver Disease Diagnosis and Treatment
- Influenza Virus Research Studies
- Phagocytosis and Immune Regulation
- Eicosanoids and Hypertension Pharmacology
- Cardiac Arrest and Resuscitation
- interferon and immune responses
- Energy and Environment Impacts
- Biomarkers in Disease Mechanisms
- Cancer-related Molecular Pathways
- RNA modifications and cancer
University of Chicago
2016-2025
Pulmonary and Critical Care Associates
2009-2020
Northwestern University
2009-2016
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
2012
University of Pennsylvania
2005-2009
UPMC Hillman Cancer Center
2006-2009
Cancer Research Institute
2006-2009
Otto Warburg's theory on the origins of cancer postulates that tumor cells have defects in mitochondrial oxidative phosphorylation and therefore rely high levels aerobic glycolysis as major source ATP to fuel cellular proliferation (the Warburg effect). This is contrast normal cells, which primarily utilize for growth survival. Here we report function glucose metabolism Kras-induced anchorage-independent growth, a hallmark transformed support pentose phosphate pathway. The glycolytic under...
The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual during that important for disease pathogenesis.
Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression. How diminishes tumor growth is not fully understood. In this study, we report in human cells, inhibits mitochondrial complex I (NADH dehydrogenase) activity cellular respiration. Metformin inhibited proliferation presence of glucose, but induced cell death upon glucose deprivation, indicating cells rely exclusively on glycolysis for survival metformin. also reduced...
Nuclear lamin B1 (LB1) is a major structural component of the nucleus that appears to be involved in regulation many nuclear functions. The results this study demonstrate LB1 expression WI-38 cells decreases during cellular senescence. Premature senescence induced by oncogenic Ras also through retinoblastoma protein (pRb)-dependent mechanism. Silencing slows cell proliferation and induces premature cells. effects silencing on require activation p53, but not pRb. However, induction requires...
Skin development requires reactive oxygen species generated by mitochondria in keratinocytes.
Exposure of cells to endoplasmic reticulum (ER) stress leads activation PKR-like ER kinase (PERK), eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation, repression cyclin D1 translation, and subsequent cell cycle arrest in G1 phase. However, whether PERK is solely responsible for regulating accumulation after unfolded protein response pathway (UPR) has not been assessed. Herein, we demonstrate that UPR occurs independently PERK, but it remains dependent on eIF2alpha...
Hemodynamic forces regulate vascular functions. Disturbed flow (DF) occurs in arterial bifurcations and curvatures, activates endothelial cells (ECs), results inflammation ultimately atherosclerosis. However, how DF alters EC metabolism, whether resulting metabolic changes induce activation, is unknown. Using transcriptomics bioenergetic analysis, we discovered that induces glycolysis reduces mitochondrial respiratory capacity human aortic ECs. DF-induced reprogramming required hypoxia...
Idiopathic pulmonary fibrosis (IPF) is characterized by the transforming growth factor (TGF)-β-dependent differentiation of lung fibroblasts into myofibroblasts, leading to excessive deposition extracellular matrix proteins, which distort architecture and function. Metabolic reprogramming in myofibroblasts emerging as an important mechanism pathogenesis IPF, recent evidence suggests that glutamine metabolism required although exact role unclear. In present study, we demonstrate its...
To maintain cellular ATP levels, hypoxia leads to Na,K-ATPase inhibition in a process dependent on reactive oxygen species (ROS) and the activation of AMP-activated kinase α1 (AMPK-α1). We report here that during AMPK does not require liver B1 (LKB1) but requires release Ca2+ from endoplasmic reticulum (ER) redistribution STIM1 ER-plasma membrane junctions, leading calcium entry via release-activated (CRAC) channels. This increase intracellular induces Ca2+/calmodulin-dependent β...
TGF-β promotes excessive collagen deposition in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). The amino acid composition of is unique due to its high (33%) glycine content. Here, we report that induces expression glycolytic genes and increases flux. also the enzymes de novo serine synthesis pathway (phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), phosphatase (PSPH)) (serine hydroxymethyltransferase 2 (SHMT2)). Studies fibroblasts with...
Notch plays a critical role in the transition from proliferation to differentiation epidermis and corneal epithelium. Furthermore, aberrant signaling is feature of diseases like psoriasis, eczema, nonmelanoma skin cancer, melanoma where are impaired. Whereas much known about downstream events following signaling, factors responsible for negatively regulating receptor after ligand activation incompletely understood. can undergo hydroxylation by factor-inhibiting hypoxia-inducible factor 1...
Macrophage effector function is dynamic in nature and largely dependent on not only the type of immunological challenge but also tissue-specific environment developmental origin a given macrophage population. Recent research has highlighted importance glycolytic metabolism regulation as common feature associated with activation. Yet, most used cell lines bone marrow-derived macrophages, which do account for diversity populations role tissue specificity immunometabolism. Tissue-resident...
Protein misfolding in the endoplasmic reticulum (ER) triggers a signaling pathway termed unfolded protein response path-way (UPR). UPR is transduced through transmembrane ER effectors PKR-like kinase (PERK), inositol requiring kinase-1 (IRE-1), and activating transcription factor 6 (ATF6). PERK activation phosphorylation of eIF2alpha leading to repression synthesis, thereby relieving load directly inhibiting cyclin D1 translation contributing cell cycle arrest. However, PERK(-/-) murine...