A5017506878- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Cancer, Lipids, and Metabolism
- Medical Imaging Techniques and Applications
- Immune Cell Function and Interaction
- Adipose Tissue and Metabolism
- Biochemical and Molecular Research
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Hedgehog Signaling Pathway Studies
- T-cell and B-cell Immunology
- Pancreatic function and diabetes
- Folate and B Vitamins Research
- Renal cell carcinoma treatment
- Autophagy in Disease and Therapy
- Retinoids in leukemia and cellular processes
- Cancer therapeutics and mechanisms
- Glioma Diagnosis and Treatment
- Diet and metabolism studies
Children's Medical Center
2016-2025
University of Chicago
2022-2025
The University of Texas Southwestern Medical Center
2016-2025
University of Chicago Medicine Comprehensive Cancer Center
2023
Southwestern Medical Center
2019-2020
McGill University Health Centre
2010-2017
McGill University
2010-2017
Brock University
2010-2015
AMPK is a metabolic sensor that helps maintain cellular energy homeostasis. Despite evidence linking with tumor suppressor functions, the role of in tumorigenesis and metabolism unknown. Here we show negatively regulates aerobic glycolysis (the Warburg effect) cancer cells suppresses growth vivo. Genetic ablation α1 catalytic subunit accelerates Myc-induced lymphomagenesis. Inactivation AMPKα both transformed nontransformed promotes shift to glycolysis, increased allocation glucose carbon...
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...
Reactive oxygen species (ROS) are continuously produced as a by-product of mitochondrial metabolism and eliminated via antioxidant systems. Regulation mitochondrially ROS is required for proper cellular function, adaptation to metabolic stress, bypassing senescence. Here, we report non-canonical regulation the energy sensor AMP-activated protein kinase (AMPK) by (mROS) that functions maintain homeostasis. We demonstrate physiological activator AMPK activation triggers PGC-1α-dependent...
Tumor cells gain a survival/growth advantage by adapting their metabolism to respond environmental stress, process known as metabolic transformation. The best-known aspect of transformation is the Warburg effect, whereby cancer up-regulate glycolysis under aerobic conditions. However, other mechanisms mediating remain undefined. Here we report that carnitine palmitoyltransferase 1C (CPT1C), brain-specific enzyme, may participate in CPT1C expression correlates inversely with mammalian target...
The mammalian adenosine monophosphate-activated protein kinase (AMPK) is a serine-threonine complex that central regulator of cellular energy homeostasis. However, the mechanisms by which AMPK mediates responses to metabolic stress remain unclear. We found activates transcription through direct association with chromatin and phosphorylation histone H2B at serine 36. recruitment Ser36 colocalized within genes activated AMPK-dependent pathways, both in promoters transcribed regions. Ectopic...
Significance Liver kinase B1 (LKB1) is a serine/threonine often inactivated in human cancer. We demonstrate here that loss of LKB1 expression cancer cells promotes progrowth metabolic profile enables increased cell growth and proliferation. Loss tumor metabolism through mammalian target rapamycin complex 1- reactive oxygen species-dependent increases hypoxia-inducible factor-1α (HIF-1α). LKB1-null are dependent on HIF-1α to maintain cellular ATP viability under poor nutrient conditions,...
Metformin is a biguanide widely prescribed to treat Type II diabetes that has gained interest as an antineoplastic agent. Recent work suggests metformin directly antagonizes cancer cell growth through its actions on complex I of the mitochondrial electron transport chain (ETC). However, mechanisms by which arrests proliferation remain poorly defined. Here we demonstrate metabolic checkpoint kinases AMP-activated protein kinase (AMPK) and LKB1 are not required for antiproliferative effects...
How environmental nutrient availability impacts T cell metabolism and function remains poorly understood. Here, we report that the presence of physiologic carbon sources (PCSs) in culture medium broadly glucose utilization by CD8+ cells, independent transcriptional changes metabolic reprogramming. The PCSs reduced contribution to TCA cycle increased effector with lactate directly fueling cycle. In fact, cells responding Listeria infection preferentially consumed over as a substrate vitro,...
Abstract Mammalian embryogenesis requires rapid growth and proper metabolic regulation 1 . Midgestation features increasing oxygen nutrient availability concomitant with fetal organ development 2,3 Understanding how metabolism supports approaches to observe directly in model organisms utero. Here we used isotope tracing metabolomics identify evolving programmes the placenta embryo during midgestation mice. These tissues differ metabolically throughout midgestation, but pinpointed gestational...
Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks functioning as regulatory molecules. However, the mechanisms which circulating in body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8
Abstract Background Glutamine metabolism is a central metabolic pathway in cancer. Recently, reductive carboxylation of glutamine for lipogenesis has been shown to constitute key anabolic route cancer cells. However, little known regarding regulators the various pathways Methods The impact PGC-1α and ERRα on enzyme expression was assessed ERBB2+ breast cell lines with quantitative RT-PCR, chromatin immunoprecipitation, immunoblotting experiments. flux quantified using 13 C-labeled GC/MS...