A5076473304- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- Mechanisms of cancer metastasis
- Ferroptosis and cancer prognosis
- Lung Cancer Treatments and Mutations
- Cancer Mechanisms and Therapy
- Medical Imaging and Pathology Studies
- Metabolism, Diabetes, and Cancer
- Melanoma and MAPK Pathways
- Cancer Research and Treatments
- Mitochondrial Function and Pathology
- PI3K/AKT/mTOR signaling in cancer
- Microtubule and mitosis dynamics
- Cancer, Lipids, and Metabolism
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Metabolomics and Mass Spectrometry Studies
- Cancer-related gene regulation
- PARP inhibition in cancer therapy
- Medical Imaging Techniques and Applications
- Autophagy in Disease and Therapy
- Lung Cancer Research Studies
- Machine Learning in Bioinformatics
University of California, Los Angeles
2015-2024
UCLA Jonsson Comprehensive Cancer Center
2018-2024
APLA Health
2012-2024
University of Washington
2020-2021
UCLA Health
2020
University of California System
2019
Salk Institute for Biological Studies
2008-2018
The University of Texas Southwestern Medical Center
2014
University of California, San Diego
2013
Neurological Surgery
2013
Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In screen for substrates AMPK, we identified ULK1 ULK2, mammalian orthologs the yeast Atg1, which required autophagy. Genetic analysis AMPK or liver Caenorhabditis elegans revealed requirement these kinases mammals, loss resulted aberrant accumulation autophagy adaptor p62 defective mitophagy. Reconstitution...
Article14 October 2019Open Access Source DataTransparent process Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent Dane M Wolf Department of Medicine (Endocrinology), Molecular Medical Pharmacology, David Geffen School Medicine, University California, Los Angeles, CA, USA Graduate Program in Nutrition Metabolism, Sciences, Boston Boston, MA, Search for more papers by this author Mayuko Segawa Arun Kumar Kondadi Institute...
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,...
Abstract Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters may lead potential treatments COVID-19. Here we profile metabolic changes conferred by infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, show that increases glucose carbon entry into TCA cycle via increased pyruvate carboxylase expression. also reduces oxidative glutamine while maintaining reductive carboxylation....
Abstract Mitochondria are critical to the governance of metabolism and bioenergetics in cancer cells 1 . The mitochondria form highly organized networks, which their outer inner membrane structures define bioenergetic capacity 2,3 However, vivo studies delineating relationship between structural organization mitochondrial networks activity have been limited. Here we present an functional analysis phenotypes non-small cell lung (NSCLC) using integrated platform consisting positron emission...
Peutz-Jeghers syndrome (PJS) is a familial cancer disorder due to inherited loss of function mutations in the LKB1/ STK11 serine/threonine kinase. PJS patients develop gastrointestinal hamartomas with 100% penetrance often second decade life, and demonstrate an increased predisposition toward development number additional malignancies. Among mitogenic signaling pathways, mammalian-target rapamycin complex 1 (mTORC1) pathway hyperactivated tissues tumors derived from LKB1-deficient mice....
Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic biosynthetic demands proliferation. We tested small-molecule inhibitor glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy simultaneously impair glutamine utilization thereby suppress tumor growth. Here, we show that cooperates drive energetic stress activate AMP-activated...
Lung premalignancy and early-stage adenocarcinoma use a mechanism of glucose transport that can be targeted for early diagnosis treatment.
Abstract Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small lung cancer (NSCLC) distinct in their histological, molecular clinical presentation. However, metabolic signatures specific to individual NSCLC remain unknown. Here, we perform an integrative analysis human tumour samples, patient-derived xenografts, murine model NSCLC, lines The Cancer Genome Atlas (TCGA) reveal a markedly elevated expression GLUT1 glucose transporter SqCC, which...
Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are primary pathological driver progression, yet how various microenvironmental influences, such as hypoxia, contribute to their sustained activation and differentiation is poorly understood. As a defining feature hypoxia its impact on cellular metabolism, we sought investigate hypoxia-induced metabolic reprogramming affects myofibroblast test preclinical efficacy targeting...
Glioblastoma (GBM) is the most aggressive primary brain tumor with poor prognosis. Here, we studied effects of phenformin, a mitochondrial complex I inhibitor and more potent chemical analog diabetes drug metformin on inhibition cell growth induction apoptosis glioma stem cells (GSCs) using both in vitro vivo models. Phenformin inhibited self-renewal GSCs, decreased expression stemness mesenchymal markers increased miR-124, 137 let-7. Silencing let-7 abrogated phenformin GSCs via pathway...
Squamous cell carcinoma (SCC), a malignancy arising across multiple anatomical sites, is responsible for significant cancer mortality due to insufficient therapeutic options. Here, we identify exceptional glucose reliance among SCCs dictated by hyperactive GLUT1-mediated influx. Mechanistically, squamous lineage transcription factors p63 and SOX2 transactivate the intronic enhancer cluster of SLC2A1. Elevated influx fuels generation NADPH GSH, thereby heightening anti-oxidative capacity in...
MAPK targeting in cancer often fails due to reactivation. MEK inhibitor (MEKi) monotherapy provides limited clinical benefits but may serve as a foundation for combination therapies. Here, we showed that combining type II RAF (RAFi) with an allosteric MEKi durably prevents and overcomes acquired resistance among cancers KRAS, NRAS, NF1, BRAF non-V600, V600 mutations. Tumor cell-intrinsically, RAFi plus sequester complexes, reduce MEK/MEK dimerization, uncouple from ERK acquired-resistant...
Significance Reduced oxygen supply—hypoxia—is a near-universal feature of solid tumors that can alter how respond to therapies. We investigated the transition from normoxia hypoxia in model brain cancer systems, using single-cell proteomics and data analysis tools based on physicochemical concepts. This approach permits simplification otherwise complex biology. find hypoxia-induced switch within mammalian target rapamycin (mTOR) signaling network. At switching point, mTOR is predicted, then...
Recent breakthroughs in live-cell imaging have enabled visualization of cristae, making it feasible to investigate the structure-function relationship cristae real time. However, quantifying images an unbiased way remains challenging. Here, we present a novel, semi-automated approach quantify using machine-learning Trainable Weka Segmentation tool. Compared with standard techniques, our not only avoids bias associated manual thresholding but more efficiently segments from Airyscan and...