A5039699766- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- Cancer-related gene regulation
- DNA Repair Mechanisms
- Histone Deacetylase Inhibitors Research
- Melanoma and MAPK Pathways
- Fibroblast Growth Factor Research
- Advanced biosensing and bioanalysis techniques
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- Telomeres, Telomerase, and Senescence
- Cancer Genomics and Diagnostics
- Metabolism, Diabetes, and Cancer
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Protein Degradation and Inhibitors
- Cancer Research and Treatments
- DNA and Nucleic Acid Chemistry
- interferon and immune responses
- Lung Cancer Treatments and Mutations
University of Alabama at Birmingham
2019-2025
University of Massachusetts Chan Medical School
2007-2023
Howard Hughes Medical Institute
2007-2023
Yale University
2010-2019
Yale Cancer Center
2014-2018
University of New Haven
2013
Boston University
2009
Indian Institute of Science Bangalore
2003-2006
Zero to Three
2005
Ceramides are sphingolipids that act as signaling molecules involved in regulating cellular processes including apoptosis, proliferation, and metabolism. Deregulation of ceramide metabolism contributes to cancer development progression. Therefore, regulation levels cells is being explored a new approach for therapy. This review discusses the multiple roles ceramides strategies modulate attenuate cell survival metabolic pathways, while activating apoptotic mechanisms, making them...
Significance Natural killer (NK) cells play an important role as a first line of immunological defense against tumor initiation. However, cancer cell intrinsic factors that regulate NK activity are not fully known. We performed chemical genetics screen using small-molecule inhibitors epigenetic and identified Enhancer zeste homolog 2 (EZH2) key regulator cell-mediated eradication hepatocellular carcinoma cells. These results uncover EZH2 in the regulation mechanism to promote oncogenesis....
Oncogenic mutations in BRAF and NRAS occur 70% of melanomas. In this study, we identify a microRNA, miR-146a, that is highly upregulated by oncogenic NRAS. Expression miR-146a increases the ability human melanoma cells to proliferate culture form tumors mice, whereas knockdown has opposite effects. We show these activities are due targeting NUMB mRNA, repressor Notch signaling. Previous studies have shown pre-miR-146a contains single nucleotide polymorphism (C>G rs2910164). find...
Significance In somatic cells of female mammals, one the two X chromosomes is randomly silenced, a phenomenon called X-chromosome inactivation (XCI). XCI initiated in cis by noncoding RNA Xist , but trans -acting factors that mediate remain largely unknown. this study, we perform large-scale interference screen and identify new are required for mammalian XCI. Chemical inhibitors some these can reversibly reactivate inactive chromosome. Our results have therapeutic implications certain human...
Abstract Insulin resistance is a key driver of type 2 diabetes (T2D) and characterized by defective insulin receptor (INSR) signalling. Although surface INSR downregulation well-established contributor to resistance, the underlying molecular mechanisms remain obscure. Here we show that E3 ubiquitin ligase MARCH1 impairs cellular action degrading cell INSR. Using large-scale RNA interference screen, identify as negative regulator March1 loss-of-function enhances, overexpression impairs,...
Silencing of MLH1 is frequently seen in sporadic colorectal cancers. We show here that hypoxia causes decreased histone H3 lysine 4 (H3K4) methylation at the promoter via action H3K4 demethylases LSD1 and PLU-1 promotes durable long-term silencing a pathway requires LSD1. Knockdown or its corepressor, CoREST, also prevents resilencing (and associated cytosine DNA methylation) endogenous RKO colon cancer cells following transient reactivation by treatment with methyltransferase inhibitor...
Highlights•MELK is upregulated in melanoma by the MAPK pathway via E2F1•MELK inhibition blocks growth•MELK phosphorylates a large number of BRAF and MEK substrates•MELK partly promotes stimulating NF-κB SQSTM1SummaryMelanoma accounts for more than 80% skin cancer-related deaths, current therapies provide only short-term benefit to patients. Here, we show cells that maternal embryonic leucine zipper kinase (MELK) transcriptionally transcription factor E2F1. MELK knockdown or pharmacological...
Enhancer of zeste homolog 2 (EZH2) is a histone H3 lysine 27 methyltransferase that has been shown to function as an oncogene in some cancers. Previous reports have largely focused on the ability EZH2 regulate cell-intrinsic tumor regulatory pathways its mechanism-of-oncogenic action. However, role EZH2-mediated immune suppression plays oncogenic activity not fully known. In particular, natural killer (NK) cells EZH2-driven growth remains incompletely understood. Here, we demonstrate genetic...
Activator protein 2alpha (AP-2alpha) is a sequence-specific DNA-binding transcription factor implicated in differentiation and transformation. In this study, we have made replication-deficient recombinant adenovirus that expresses functional AP-2alpha (Ad-AP2). Cells infected with Ad-AP2 expressed induced levels of protein, which bound to DNA manner activated the AP-2-specific reporter 3X-AP2. Expression from inhibited cellular synthesis apoptosis. infection resulted efficient inhibition...
Oncogene-induced DNA methylation-mediated transcriptional silencing of tumor suppressors frequently occurs in cancer, but the mechanism and functional role this oncogenesis are not fully understood. Here, we show that oncogenic epidermal growth factor receptor (EGFR) induces multiple unrelated lung adenocarcinomas glioblastomas by inhibiting demethylase TET oncogene family member 1 (TET1) via C/EBPα transcription factor. After EGFR inhibition, TET1 binds to suppressor promoters their...
Multiple endocrine neoplasia type 1 is a familial cancer syndrome resulting from loss-of-function mutations in the MEN1 gene. We previously identified tumor suppressor as gene required for oncogene-induced senescence melanocytes, raising possibility that melanoma suppressor. Here we show expression lost high percentage of human melanomas and cell lines. find melanocytes depleted are deficient homologous recombination (HR)-directed DNA repair, which accompanied by increased nonhomologous...