A5015440896- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- Bacteriophages and microbial interactions
- interferon and immune responses
- RNA Research and Splicing
- DNA Repair Mechanisms
- Heat shock proteins research
- Cancer-related molecular mechanisms research
- Advanced biosensing and bioanalysis techniques
- Cancer-related Molecular Pathways
- Hippo pathway signaling and YAP/TAZ
- ATP Synthase and ATPases Research
- Cytokine Signaling Pathways and Interactions
- Liver physiology and pathology
- Pluripotent Stem Cells Research
- Protein Structure and Dynamics
- FOXO transcription factor regulation
- Prenatal Substance Exposure Effects
- Skin Protection and Aging
University of Southern California
2010-2023
Keck Hospital of USC
2019
Stanford Medicine
2005-2016
Southern California University for Professional Studies
2013
Southern California Reproductive Center
2012
Center of Molecular Immunology (Cuba)
2011
Stanford University
1999-2007
Tumor-initiating stem-like cells (TICs) are resistant to chemotherapy and associated with hepatocellular carcinoma (HCC) caused by HCV and/or alcohol-related chronic liver injury. Using Tg mouse models patients HCC, we isolated CD133(+) TICs identified the pluripotency marker NANOG as a direct target of TLR4, which drives tumor-initiating activity TICs. These TLR4/NANOG-dependent were defective in TGF-β tumor suppressor pathway. Functional oncogene screening TIC cDNA library Yap1 Igf2bp3...
Adenine N6 methylation in DNA (6mA) is widespread among bacteria and phage detected mammalian genomes, where its function largely unexplored. Here we show that 6mA deposition removal are catalyzed by the Mettl4 methyltransferase Alkbh4 dioxygenase, respectively, accumulation genic elements corresponds with transcriptional silencing. Inactivation of murine depletes causes sublethality craniofacial dysmorphism incross progeny. We identify distinct sensor domains prokaryotic origin within MPND...
Programmed cell suicide of infected bacteria, known as abortive infection (Abi), serves an immune defense strategy to prevent the propagation bacteriophage viruses. Many Abi systems utilize bespoke cyclic nucleotide messengers generated upon mobilize cognate death effectors. Here, we identify a family nucleotidyltransferases (NTases) that synthesize competitor dinucleotide (CDN) ligands and inhibit TIR NADase effectors activated via linked STING CDN sensor domain (TIR-STING). Through...
Abstract Hypoxia activates all components of the unfolded protein response (UPR), a stress initiated by accumulation proteins within endoplasmic reticulum (ER). Our group and others have shown previously that UPR, hypoxia-inducible factor–independent signaling pathway, mediates cell survival during hypoxia is required for tumor growth. Identifying new genes pathways are important ER may lead to discovery targets in cancer therapy. Using set 4,728 homozygous diploid deletion mutants budding...
Misregulation of a pluripotency-associated transcription factor network in adult tissues is associated with the expansion rare, highly malignant tumor-initiating stem cells (TISCs) through poorly understood mechanisms. We demonstrate that robust and selective expression receptor for adipocyte-derived peptide hormone leptin (OB-R) characteristic feature TISCs broad array embryonic induced pluripotent mediated directly by core factors OCT4 SOX2. exhibit sensitized responses to leptin,...
Stem cell populations are maintained through self-renewing divisions in which one daughter commits to a particular fate whereas the other retains multipotent characteristics of its parent. The NUMB, tumor suppressor, conjunction with another tumor-suppressor protein, p53, preserves this property and acts as barrier against deregulated expansion tumor-associated stem cells. In context, NUMB-p53 interaction plays crucial role maintain proper homeostasis both cells, well differentiated Because...
Enzymatic oxidation of 5-methylcytosine (5mC) in DNA by the Tet dioxygenases reprograms genome function embryogenesis and postnatal development. Tet-oxidized derivatives 5mC such as 5-hydroxymethylcytosine (5hmC) act transient intermediates demethylation or persist durable marks, yet how these alternative fates are specified at individual CpGs is not understood. Here, we report that SOS response-associated peptidase (SRAP) domain protein Srap1, mammalian ortholog an ancient superfamily...
Abstract RNA-binding protein Musashi 2 (MSI2) is elevated in several cancers and linked to poor prognosis. Here, we tested if MSI2 promotes MYC viral mRNA translation induce self-renewal via an internal ribosome entry sequence (IRES). We performed RIP-seq using anti-MSI2 antibody tumor-initiating stem-like cells (TICs). binds the site (IRES)-containing oncogene mRNAs including MYC, JUN VEGFA as well HCV IRES increase their synthesis promote tumor-initiation at post-transcriptional level. a...
Stem cell populations are maintained through self-renewing divisions in which one daughter commits to a specific fate while the other retains multipotent characteristics of its parent. The p53 tumor suppressor, conjunction with interacting partner protein Numb, preserves this asymmetry and functions as vital barrier against unchecked expansion stem pools; however, little is known about biological control Numb-p53 interaction. We show here that Numb constituents high molecular mass complex,...
3514 Background: The unfolded protein response (UPR) is an adaptive to the toxic accumulation of misfolded proteins in endoplasmic reticulum (ER), and activated solid tumors. IRE1a a core component UPR responds ER stress through activation its dual kinase endonuclease domains. splices mRNA for XBP-1, generateing potent transcription factor that required tumor growth. Methods: We developed fibrosarcoma cell line expressing fusion unprocessed XBP-1 inserted upstream firefly luciferase. Under...
Summary Programmed cell suicide of infected bacteria, known as abortive infection (Abi), serves a central immune defense strategy to prevent the spread bacteriophage viruses and other invasive genetic elements across population. Many Abi systems utilize bespoke cyclic nucleotide messengers generated upon rapidly mobilize cognate death effectors. Here, we identify large family nucleotidyltransferases (NTases) that synthesize competitor dinucleotide (CDN) ligands, inhibiting NAD-depleting TIR...
Abstract Backgrounds and Aims: RNA-binding protein MSI2 is elevated in several cancers linked to poor prognosis. Here, we sought elucidate the role of regulating expression proto-oncogenes or tumor suppressor genes hepatocellular carcinoma (HCC). Methods: We performed RIP-seq using anti-MSI2 antibody tumor-initiating stem-like cells (TICs) subsequent validation by qPCR analysis. Results: Among MSI2-bound RNAs, MYC mRNA long noncoding RNA (LncRNA) miR22 host gene (MIR22HG) MARAT1 were...