et al

PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells

Published date : 09 Jul 2018

Oncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, the senescence-associated secretory phenotype (SASP) is a potential therapeutic target. Here, we describe an RNAi screen for SASP regulators. We identified 50 druggable targets whose knockdown suppresses the inflammatory secretome and differentially affects other SASP components. Among the screen candidates was PTBP1.

type
Journal Paper
journal
Cancer Cell, Vol. 34, Issue 1, Pg 85-102, 9 July 2018, doi: 10.1016/j.ccell.2018.06.007,
Impact Factor
22.844

SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements

Published date : 19 Jun 2018

The RNA-binding protein SRSF3 (also known as SRp20) has critical roles in the regulation of pre-mRNA splicing. Zygotic knockout of Srsf3 results in embryo arrest at the blastocyst stage. However, SRSF3 is also present in oocytes, suggesting that it might be critical as a maternally inherited factor. Here we identify SRSF3 as an essential regulator of alternative splicing and of transposable elements to maintain transcriptome integrity in mouse oocyte.

type
Journal Paper
journal
Cell Discovery 4, Article no: 33 (2018), doi: 10.1038/s41421-018-0032-3
Impact Factor
4.462

A novel community driven software for functional enrichment analysis of extracellular vesicles data

Published date : 26 May 2017

Bioinformatics tools are imperative for the in depth analysis of heterogeneous high-throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture “what the community needs in a tool”. Here, we describe a novel community-driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes.

type
Journal Paper
journal
Journal of Extracellular Vesicles 2017, Vol. 6, 2017, Issue 1, doi: 10.1080/20013078.2017.1321455
Impact Factor
4.259

Retinoic Acid Mediates Visceral-specific Adipogenic Defects of Human Adipose-derived Stem Cells

Published date : 07 Mar 2016

Increased visceral fat, rather than subcutaneous fat, during obesity onset is associated with higher risk of developing metabolic diseases. Human adipose-derived stem cells(ASCs) from visceral depots are compromised in their inherent adipogenic properties compared to ASCs from subcutaneous depots, but little is known about the underlying mechanisms. By ontology analysis of global gene expression studies, we demonstrate that many genes involved in retinoic acid (RA) synthesis or regulated by RA are differentially expressed in human tissues and ASCs from subcutaneous and visceral fat.

type
Journal Paper
journal
Diabetes, 2 Mar 2016, doi: 10.2337/db15-1315
Impact Factor
8.474

Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in human subjects

Published date : 30 Sep 2013

BACKGROUND: Atopic dermatitis (AD) is a major inflammatory condition of the skin caused by inherited skin barrier deficiency, with mutations in the filaggrin gene predisposing to development of AD. Support for barrier deficiency initiating AD came from flaky tail mice, which have a frameshift mutation in Flg and also carry an unknown gene, matted, causing a matted hair phenotype.

OBJECTIVE: We sought to identify the matted mutant gene in mice and further define whether mutations in the human gene were associated with AD.

type
Journal Paper
journal
The Journal of Allergy and Clinical Immunology, 28 Sep 2013, doi: 10.1016/j.jaci.2013.08.046
Impact Factor
12.047

Tysnd1 Deficiency in Mice Interferes with the Peroxisomal Localization of PTS2 Enzymes, Causing Lipid Metabolic Abnormalities and Male Infertility

Published date : 14 Feb 2013

Peroxisomes are subcellular organelles involved in lipid metabolic processes, including those of very-long-chain fatty acids and branched-chain fatty acids, among others. Peroxisome matrix proteins are synthesized in the cytoplasm. Targeting signals (PTS or peroxisomal targeting signal) at the C-terminus (PTS1) or N-terminus (PTS2) of peroxisomal matrix proteins mediate their import into the organelle. In the case of PTS2-containing proteins, the PTS2 signal is cleaved from the protein when transported into peroxisomes.

type
Journal Paper
journal
PLOS Genetics, Feb 2013, Vol. 9, Issue 2, doi:10.1371/journal.pgen.1003286
Impact Factor
8.694

Effects of Hydrogen Peroxide on Wound Healing in Mice in Relation to Oxidative Damage

Published date : 04 Oct 2012

It has been established that low concentrations of hydrogen peroxide (H2O2) are produced in wounds and is required for optimal healing. Yet at the same time, there is evidence that excessive oxidative damage is correlated with poor-healing wounds. In this paper, we seek to determine whether topical application of H2O2 can modulate wound healing and if its effects are related to oxidative damage. Using a C57BL/6 mice excision wound model, H2O2 was found to enhance angiogenesis and wound closure at 10 mM but retarded wound closure at 166 mM.

type
Journal Paper
journal
PLoS ONE Nov 2012, Vol. 7, Issue 11, doi: 10.1371/journal.pone.0049215
Impact Factor
4.092

SALIGN: a web server for alignment of multiple protein sequences and structures

Published date : 21 May 2012

ABSTRACT
Summary: Accurate alignment of protein sequences and/or structures is crucial for many biological analyses, including
functional annotation of proteins, classifying protein sequences into families, and comparative protein structure modeling. Described
here is a web interface to SALIGN, the versatile protein multiple sequence/structure alignment module of MODELLER. The web
server automatically determines the best alignment procedure based on the inputs, while allowing the user to override default parameter

type
Journal Paper
journal
Bioinformatics. 2012 Aug 1;28(15):2072-3. doi: 10.1093/bioinformatics/bts302
Impact Factor
5.468

Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic for FOS protein in invasive tumors

Published date : 19 Jan 2012

Ecotropic viral integration site 1 (EVI1) is an oncogenic dual domain zinc finger transcription factor that plays an essential role in the regulation of hematopoietic stem cell renewal, and its overexpression in myeloid leukemia and epithelial cancers is associated with poor patient survival. Despite the discovery of EVI1 in 1988 and its emerging role as a dominant oncogene in various types of cancer, few EVI1 target genes are known. This lack of knowledge has precluded a clear understanding of exactly how EVI1 contributes to cancer.

type
Journal Paper
journal
PNAS, 2012 Feb 7;109(6):2168-73. doi: 10.1073/pnas.1119229109
Impact Factor
9.681

Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance

Published date : 12 Jan 2012

The asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a) acts as a repressive mark that antagonizes trimethylation of H3 lysine 4. Here we report that H3R2 is also symmetrically dimethylated (H3R2me2s) by PRMT5 and PRMT7 and present in euchromatic regions. Profiling of H3-tail interactors by SILAC MS revealed that H3R2me2s excludes binding of RBBP7, a central component of co-repressor complexes Sin3a, NURD and PRC2. Conversely H3R2me2s enhances binding of WDR5, a common component of the coactivator complexes MLL, SET1A, SET1B, NLS1 and ATAC.

type
Journal Paper
journal
Nature Structural & Molecular Biology, 19, Pg 136–144, (2012), doi:10.1038/nsmb.2209
Impact Factor
12.712