A5044758224- Protein Kinase Regulation and GTPase Signaling
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
- Melanoma and MAPK Pathways
- Metabolism, Diabetes, and Cancer
- RNA Interference and Gene Delivery
- Enzyme Structure and Function
- Protein Degradation and Inhibitors
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- Ion channel regulation and function
- Gallbladder and Bile Duct Disorders
- DNA Repair Mechanisms
- Medical Imaging Techniques and Applications
- Neuroblastoma Research and Treatments
- Cancer Mechanisms and Therapy
- Mitochondrial Function and Pathology
- MicroRNA in disease regulation
National Cancer Institute
2016-2025
Center for Cancer Research
2016-2025
Hubei University of Medicine
2024-2025
Arizona Alzheimer’s Consortium
2017-2024
National Institutes of Health
2012-2024
Alzheimer's Association
2017-2024
Banner Alzheimer’s Institute
2017-2024
First Hospital of China Medical University
2009-2023
China Medical University
2009-2023
Baker Heart and Diabetes Institute
2023
Cellular responses to DNA damage are mediated by a number of protein kinases, including ATM (ataxia telangiectasia mutated) and ATR (ATM Rad3-related). The outlines the signal transduction portion this pathway known, but little is known about physiological scope response (DDR). We performed large-scale proteomic analysis proteins phosphorylated in on consensus sites recognized identified more than 900 regulated phosphorylation encompassing over 700 proteins. Functional subset data set...
Tumor necrosis factor (TNF) is an important inflammatory cytokine and induces many cellular responses, including inflammation, cell proliferation, apoptosis, necrosis. It known that receptor interacting protein (RIP) kinases, RIP1 RIP3, are key effectors of TNF-induced necrosis, but little about how these two RIP kinases mediate this process, although reactive oxygen species (ROS) generation JNK activation have been suggested to be downstream events kinases. Here we report the identification...
Abstract Activation of the phosphoinositide 3-kinase (PI3K) pathway has been implicated in pathogenesis a variety cancers. Recently, mutations gene encoding p110α catalytic subunit PI3K (PIK3CA) have identified several human The primarily result single amino acid substitutions, with >85% either exon 9 or 20. Multiple studies shown that these are observed 18% to 40% breast However, phenotypic effects PIK3CA not examined epithelial cells. Herein, we examine activity two most common...
Myc is an oncogenic transcription factor frequently dysregulated in human cancer. To identify pathways supporting the program, we used a genome-wide RNA interference screen to search for Myc-synthetic lethal genes and uncovered role SUMO-activating enzyme (SAE1/2). Loss of SAE1/2 enzymatic activity drives synthetic lethality with Myc. Inactivation SAE2 leads mitotic catastrophe cell death upon hyperactivation. Mechanistically, inhibition switches transcriptional subprogram from activated...
Retroviral short hairpin RNA (shRNA)-mediated genetic screens in mammalian cells are powerful tools for discovering loss-of-function phenotypes. We describe a highly parallel multiplex methodology screening large pools of shRNAs using half-hairpin barcodes microarray deconvolution. carried out dropout that affect cell proliferation and viability cancer normal cells. identified many to be antiproliferative target core cellular processes, such as the cycle protein translation, all examined....
Normal food intake and body weight homeostasis require the direct action of leptin on hypothalamic proopiomelanocortin (POMC) neurons. It has been proposed that requires PI3K activity. We therefore assessed contribution signaling to leptin's effects POMC neurons organismal energy balance. Leptin caused a rapid depolarization an increase in potential frequency patch-clamp recordings slices. Pharmacologic inhibition prevented this increased firing rate, indicating PI3K-dependent mechanism...
Class I(A) phosphoinositide 3-kinases (PI3Ks) are activated by growth factor receptors, and they regulate, among other processes, cell organ size. Studies using transgenic mice overexpressing constitutively active dominant negative forms of the p110alpha catalytic subunit class PI3K have implicated role this enzyme in regulating heart size physiological cardiac hypertrophy. To further understand controlling to circumvent potential complications from overexpression proteins, we generated with...
Cancer Gene Islands Human tumors are riddled with genomic alterations that rearrange, remove, amplify, or otherwise disrupt a wide spectrum of genes, and key challenge is identifying which these causally involved in tumorigenesis. The role recurrent hemizygous focal deletions especially puzzling because preferentially affect certain chromosomal regions result the loss one copy whole cluster adjacent genes. Solimini et al. (p. 104 , published online 24 May; see Perspective by Greenman ) found...
Phosphoinositide (PI) 3-kinase is required for most insulin and insulin-like growth factor (IGF) 1–dependent cellular responses. The p85 regulatory subunit of PI to mediate the insulin-dependent recruitment plasma membrane, yet mice with reduced expression have increased sensitivity. To further understand role p85, we examined IGF-1–dependent translocation p85α by using a green fluorescence protein (GFP)–tagged (EGFP–p85α). In response IGF-1, but not PDGF signaling, EGFP–p85α translocates...
Abstract Phosphoinositide 3-kinase (PI3K) plays a critical role in tumorigenesis, and the PI3K p85 regulatory subunit exerts both positive negative effects on signaling. Expression of Pik3r1, gene encoding p85, is decreased human prostate, lung, ovarian, bladder, liver cancers, consistent with possibility that has tumor suppressor properties. We tested this hypothesis by studying mice liver-specific deletion Pik3r1 gene. These exhibited enhanced insulin growth factor signaling progressive...
KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3′ kinase, and RalGDS families, but many additional direct indirect effectors have been reported. We assessed how these contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen we knocked down 41 nodes 92 cell lines. show that every line has unique combination of dependencies, spite this...
Oncogenic mutations in the small GTPase KRAS are frequently found human cancers, and, currently, there no effective targeted therapies for these tumors. Using a combinatorial siRNA approach, we analyzed panel of mutant colorectal and pancreatic cancer cell lines their dependency on 28 gene nodes that represent canonical RAS effector pathways selected stress response pathways. We RAF node knockdown best differentiated WT cells, suggesting kinases key oncoeffectors addiction. By analyzing all...
Abstract Hepatocellular carcinoma (HCC) is a common cause of cancer-related death worldwide. As obesity and diabetes become more prevalent, the contribution non-alcoholic fatty liver disease (NAFLD) to HCC rising. Recently, we reported intrahepatic CD4 + T cells are critical for anti-tumor surveillance in NAFLD. Lipid accumulation hallmark NAFLD, which may perturb cell function. We sought investigate how lipid-rich environment influences by focusing on carnitine palmitoyltransferase (CPT)...
Cyclin-dependent kinase 6 (CDK6) is an important regulator of the cell cycle. Together with CDK4, it phosphorylates and inactivates retinoblastoma (Rb) protein.