A5103141471- Cancer Mechanisms and Therapy
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Metabolism, Diabetes, and Cancer
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- Cancer-related Molecular Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Research and Treatments
- Lung Cancer Research Studies
- Cancer Cells and Metastasis
- interferon and immune responses
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Cancer Genomics and Diagnostics
- Cellular Mechanics and Interactions
- Heat shock proteins research
- Epigenetics and DNA Methylation
- Enzyme Structure and Function
- Acute Myeloid Leukemia Research
- Lipid metabolism and biosynthesis
- Amino Acid Enzymes and Metabolism
- Medical Imaging Techniques and Applications
- 3D Printing in Biomedical Research
The University of Texas Health Science Center at San Antonio
2022-2025
The University of Texas Health Science Center at Houston
2022-2025
Florida College
2019-2022
University of Florida
2019-2022
Emory University
2011-2019
Winship Cancer Institute
2012-2019
Piedmont Cancer Institute
2019
Boston Medical Center
2011
Regulation of RNA substrate selectivity m6A demethylase ALKBH5 remains elusive. Here, we identify RNA-binding motif protein 33 (RBM33) as a previously unrecognized m6A-binding that plays critical role in ALKBH5-mediated mRNA demethylation subset transcripts by forming complex with ALKBH5. RBM33 recruits to its m6A-marked and activates activity through the removal SUMOylation. We further demonstrate is for tumorigenesis head-neck squamous cell carcinoma (HNSCC). promotes autophagy recruiting...
Small-cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. The dismal prognosis in SCLC part associated upregulation of BCL-2 family anti-apoptotic proteins, including BCL-XL and MCL-1. Unfortunately, the currently available inhibitors except inhibitors, are not clinically relevant because various on-target toxicities. We, therefore, aimed to develop effective safe strategy targeting these proteins DT2216 (our platelet-sparing degrader) AZD8055 (an mTOR...
Unravelling the regulatory programs from single-cell multi-omics data has long been one of major challenges in genomics, especially current emerging field. Currently there is a huge gap between fast-growing and effective methods for integrative analysis these inherent sparse heterogeneous data. In this study, we have developed novel method, Single-cell Multi-omics Gene co-Regulatory algorithm (SMGR), to detect coherent functional signals target genes joint RNA-sequencing (scRNA-seq) assay...
Abstract The spread of prion‐like protein aggregates is a common driver pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit clear progressive spreading pattern that correlates with severity. Clinical observation combined complementary experimental studies has shown preformed fibrils (PFF) are seeds propagate pathology by entering cells templating misfolding aggregation endogenous Tau. While several cell...
Although recent studies demonstrate active mitochondrial metabolism in cancers, the precise mechanisms through which factors contribute to cancer metastasis remain elusive. Through a customized mitochondrion RNAi screen, we identified succinyl-CoA ligase ADP-forming subunit beta (SUCLA2) as critical anoikis resistance and driver human cancers. Mechanistically, SUCLA2, but not alpha of its enzyme complex, relocates from mitochondria cytosol upon cell detachment where SUCLA2 then binds...
Canonical pyroptosis is type of programmed cell death depending on active caspase-1, and the inflammasome carries out caspase-1 activation. Here, we showed that docosahexaenoic acid (DHA) induced ovarian cancer deaths in caspase-1-dependent manner. DHA increased activity led to interleukin-1β secretion gasdermin D cleavage while disulfiram inhibited DHA-induced death, suggesting triggered pyroptosis. Intriguingly, ASC, molecule recruiting for activation, was dispensable Instead, observed...
Microtubule-associated serine/threonine kinase 1 (MAST1) is a central driver of cisplatin resistance in human cancers. However, the molecular mechanism regulating MAST1 levels cisplatin-resistant tumors unknown. Through proteomics screen, we identified heat shock protein 90 B (hsp90B) chaperone as direct binding partner essential for its stabilization. Targeting hsp90B sensitized cancer cells to predominantly through destabilization. Mechanistically, interaction with blocked ubiquitination...
How altered metabolism contributes to chemotherapy resistance in cancer cells remains unclear. Through a metabolism-related kinome RNAi screen, we identified inositol-trisphosphate 3-kinase B (ITPKB) as critical enzyme that cisplatin-resistant tumor growth. We demonstrated inositol 1,3,4,5-tetrakisphosphate (IP4), the product of ITPKB, plays role redox homeostasis upon cisplatin exposure by reducing cisplatin-induced ROS through inhibition ROS-generating enzyme, NADPH oxidase 4 (NOX4), which...
<div>Abstract<p>Isocitrate dehydrogenase 1 (IDH1) is important for reductive carboxylation in cancer cells, and the IDH1 R132H mutation plays a pathogenic role cancers including acute myeloid leukemia (AML). However, regulatory mechanisms modulating mutant and/or wild-type (WT) function remain unknown. Here, we show that two groups of tyrosine kinases (TK) enhance activation WT through preferential Y42 or Y391 phosphorylation. Mechanistically, phosphorylation occurs monomers,...
<p>Supplementary Figure S1-S7</p>
PRKCI, the gene for protein kinase Cι (PKCι), is frequently amplified in ovarian cancer and recent studies have shown that PKCι participates ovary tumorigenesis. However, it unknown whether differentially involved growth/survival between PRKCI-amplified non-amplified cells. In this study, we analyzed patient dataset revealed PRKCI only PKC family member significantly amplification associated with higher expression. Using a panel of cell lines, found abundance generally amplification....
The cancer metastasis process involves dysregulated oncogenic kinase signaling, but how this orchestrates metabolic networks and signal cascades to promote is largely unclear. Here we report that inhibition of glutamate dehydrogenase 1 (GDH1) ribosomal S6 2 (RSK2) synergistically attenuates cell invasion, anoikis resistance, immune escape in lung more evidently tumors harboring epidermal growth factor receptor (EGFR)-activating or EGFR inhibitor-resistant mutations. Mechanistically, GDH1...
Abstract Small cell lung cancer (SCLC) is a highly aggressive type of cancer. Its ability to form metastatic spread in the early stages disease accounts for high morbidity rates. Despite initial rates response most common line treatment - conventional chemotherapy, majority SCLC patients suffer from chemoresistant recurrence. Lack full understanding molecular basis driving metastasis and resistance are main obstacles developing more efficient treatments. Several recent studies reported that...
Abstract Lung cancer is the leading cause of cancer-related deaths among both men and women in United States with non-small cell lung (NSCLC) accounting for 85% all cancers. However, regardless genetic background, nearly NSCLC are dependent on upregulation glutamine metabolism survival, consequently, nonessential amino acid becomes conditionally essential to many tumors. Tumor cells generate bulk their ATP by upregulating glycolysis discarding majority glycolytic carbon as lactate, known...
Abstract Lung cancer is the leading cause of cancer-related deaths with non-small cell lung (NSCLC)accounting for 85% all cancers. Loss or inactivating mutations serine/threonine kinase STK11 encoding LKB1 protein occurs in approximately 20% adenocarcinoma (LUAD). Although treatment NSCLCs immune checkpoint inhibitors (ICI) has responded overall survival a subset patients, studies have revealed that co-occurring KRAS/LKB1 promote primary resistance to ICIs NSCLCs, mechanism which still not...