ABSTRACT
Gina DeNicola investigates the metabolism of cancer cells in vivo with a focus on NRF2 and the tumor microenvironment.
ABSTRACT
The TINCR (Terminal differentiation-Induced Non-Coding RNA) gene is selectively expressed in epithelium tissues and is involved in the control of human epidermal differentiation and wound healing. Despite its initial report as a long non-coding RNA, the TINCR locus codes for a highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we report the identification of TINCR as a tumor suppressor in squamous cell carcinoma (SCC). TINCR is upregulated by UV-induced DNA damage in a TP53-dependent manner in human keratinocytes. Decreased TINCR protein expression is prevalently found in skin and head and neck squamous cell tumors and TINCR expression suppresses the growth of SCC cells in vitro and in vivo. Consistently, Tincr knockout mice show accelerated tumor development following UVB skin carcinogenesis and increased penetrance of invasive SCCs. Finally, genetic analyses identify loss-of-function mutations and deletions encompassing the TINCR gene in SCC clinical samples supporting a tumor suppressor role in human cancer. Altogether, these results demonstrate a role for TINCR as protein coding tumor suppressor gene recurrently lost in squamous cell carcinomas.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , RNA, Long Noncoding , Animals , Mice , Humans , Ubiquitin/metabolism , Carcinoma, Squamous Cell/genetics , Genes, Tumor Suppressor , Keratinocytes/metabolism , Head and Neck Neoplasms/genetics , RNA, Long Noncoding/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , MicropeptidesABSTRACT
Yogesh Kulathu studies signaling mechanisms with a focus on ubiquitin and other post-translational modifications such as UFMylation.
Subject(s)
Protein Processing, Post-Translational , Ubiquitin , Ubiquitination , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Conjugating Enzymes/metabolismABSTRACT
Judith Agudo studies the mechanisms that adult and cancer stem cells use to evade the immune response with the goals of engineering autoimmunity- and allograft-resistant stem cells and improving the response of cancer stem cells to immunotherapy.
Subject(s)
Immunotherapy , Neoplasms , Neoplastic Stem Cells , Humans , Autoimmunity , ImmunityABSTRACT
Chii Jou Chan investigates how tissue hydraulics regulates mammalian development, with a special focus on folliculogenesis and oocyte quality control.
Subject(s)
Mammals , Oocytes , Ovarian Follicle , Animals , Oocytes/physiology , Ovarian Follicle/physiologyABSTRACT
Sachihiro Matsunaga studies the nuclear structure and chromatin dynamics of plants.
Subject(s)
Cell Nucleus , Chromatin , Plant Cells , Plants , Plants/geneticsABSTRACT
Elvan Böke investigates the mechanisms that preserve the viability of dormant oocytes.
Subject(s)
Cell Survival , Oocytes , Oocytes/cytologyABSTRACT
Dorothy Schafer investigates the role of microglia in neural circuit development and plasticity with a special focus on neurological disorders.
Subject(s)
Microglia , Nervous System Diseases , Neuronal Plasticity , Biomedical Research , NeurogenesisABSTRACT
Sara Cuylen-Haering studies the molecular mechanisms driving phase separation of chromosomes and other cellular organelles, with a special focus on biological surfactants.
Subject(s)
Chromosomes , Organelles , Chromosomes/chemistry , Organelles/chemistryABSTRACT
Sara Wickström combines biophysics, next-generation sequencing, and basic cell biology to investigate how cellular forces regulate the fate and position of stem cells within epithelial tissues.
Subject(s)
Cell Differentiation , Epithelium , Stem Cells , Biophysics , High-Throughput Nucleotide Sequencing , Stem Cells/cytologyABSTRACT
Lena Ho studies small ORF-encoded peptides (SEPs; also known as micropeptides), with a particular focus on mitochondrial SEPs, and their role in vascular biology and immunometabolism.
Subject(s)
Mitochondria , Peptides , Open Reading Frames , Peptides/geneticsABSTRACT
Ori Avinoam studies membrane remodeling with a focus on cell-to-cell fusion through the lens of correlative light and electron microscopy.
Subject(s)
Cell Fusion , Cell MembraneABSTRACT
Bo Zhong studies the regulation of the antiviral innate immunity, inflammation, and tumorigenesis by the protein ubiquitination system.
Subject(s)
Allergy and Immunology/history , Immunity, Innate , Ubiquitination , Virology/history , Animals , China , History, 21st Century , Host-Pathogen Interactions , HumansABSTRACT
Elda Grabocka investigates the role of stress granules in obesity and cancer.
Subject(s)
Cytoplasmic Granules/metabolism , Stress, Physiological , History, 20th Century , History, 21st Century , Humans , Neoplasms/metabolismABSTRACT
Rushika M. Perera studies how pancreatic cancer cells use autophagy and the lysosome to adapt to stress.
Subject(s)
Lysosomes/metabolism , Neoplasms/metabolism , Neoplasms/pathology , Animals , History, 20th Century , History, 21st Century , HumansABSTRACT
Vaishnavi Ananthanarayanan investigates the regulation of motor proteins and cytoskeleton-organelle interactions using single-molecule microscopy.
Subject(s)
Cell Biology/history , Science , Women , History, 20th Century , History, 21st Century , HumansABSTRACT
Nan Yan studies the physiological function of innate immune signaling in the absence of pathogen infection.
Subject(s)
Immunity, Innate/immunology , Signal Transduction/immunology , Animals , Host-Pathogen Interactions/immunology , HumansABSTRACT
Ye Tian investigates how mitochondrial stress signaling pathways regulate longevity using C. elegans as a model system.
Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/metabolism , Longevity , Mitochondria/metabolism , Animals , Models, Biological , Oxidative Stress , Signal TransductionABSTRACT
Gaia Pigino studies the molecular mechanisms and principles of self-organization in cilia using 3D cryo-EM.
Subject(s)
Cilia/ultrastructure , Cryoelectron Microscopy/history , Kidney/ultrastructure , Lung/ultrastructure , Academies and Institutes/history , Animals , Chlorophyta/metabolism , Chlorophyta/ultrastructure , Cilia/metabolism , Cryoelectron Microscopy/methods , Flagella/metabolism , Flagella/ultrastructure , History, 20th Century , History, 21st Century , Humans , Italy , Kidney/metabolism , Lung/metabolismABSTRACT
During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta-gonad-mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso-ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs.
