RESUMO
Gina DeNicola investigates the metabolism of cancer cells in vivo with a focus on NRF2 and the tumor microenvironment.
RESUMO
Yogesh Kulathu studies signaling mechanisms with a focus on ubiquitin and other post-translational modifications such as UFMylation.
Assuntos
Processamento de Proteína Pós-Traducional , Ubiquitina , Ubiquitinação , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
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.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Animais , Camundongos , Humanos , Ubiquitina/metabolismo , Carcinoma de Células Escamosas/genética , Genes Supressores de Tumor , Queratinócitos/metabolismo , Neoplasias de Cabeça e Pescoço/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , MicropeptídeosRESUMO
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.
Assuntos
Imunoterapia , Neoplasias , Células-Tronco Neoplásicas , Humanos , Autoimunidade , ImunidadeRESUMO
Chii Jou Chan investigates how tissue hydraulics regulates mammalian development, with a special focus on folliculogenesis and oocyte quality control.
Assuntos
Mamíferos , Oócitos , Folículo Ovariano , Animais , Oócitos/fisiologia , Folículo Ovariano/fisiologiaRESUMO
Sachihiro Matsunaga studies the nuclear structure and chromatin dynamics of plants.
Assuntos
Núcleo Celular , Cromatina , Células Vegetais , Plantas , Plantas/genéticaRESUMO
Elvan Böke investigates the mechanisms that preserve the viability of dormant oocytes.
Assuntos
Sobrevivência Celular , Oócitos , Oócitos/citologiaRESUMO
Dorothy Schafer investigates the role of microglia in neural circuit development and plasticity with a special focus on neurological disorders.
Assuntos
Microglia , Doenças do Sistema Nervoso , Plasticidade Neuronal , Pesquisa Biomédica , NeurogêneseRESUMO
Sara Cuylen-Haering studies the molecular mechanisms driving phase separation of chromosomes and other cellular organelles, with a special focus on biological surfactants.
Assuntos
Cromossomos , Organelas , Cromossomos/química , Organelas/químicaRESUMO
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.
Assuntos
Diferenciação Celular , Epitélio , Células-Tronco , Biofísica , Sequenciamento de Nucleotídeos em Larga Escala , Células-Tronco/citologiaRESUMO
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.
Assuntos
Mitocôndrias , Peptídeos , Fases de Leitura Aberta , Peptídeos/genéticaRESUMO
Ori Avinoam studies membrane remodeling with a focus on cell-to-cell fusion through the lens of correlative light and electron microscopy.
Assuntos
Fusão Celular , Membrana CelularRESUMO
Bo Zhong studies the regulation of the antiviral innate immunity, inflammation, and tumorigenesis by the protein ubiquitination system.
Assuntos
Alergia e Imunologia/história , Imunidade Inata , Ubiquitinação , Virologia/história , Animais , China , História do Século XXI , Interações Hospedeiro-Patógeno , HumanosRESUMO
Elda Grabocka investigates the role of stress granules in obesity and cancer.
Assuntos
Grânulos Citoplasmáticos/metabolismo , Estresse Fisiológico , História do Século XX , História do Século XXI , Humanos , Neoplasias/metabolismoRESUMO
Rushika M. Perera studies how pancreatic cancer cells use autophagy and the lysosome to adapt to stress.
Assuntos
Lisossomos/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Animais , História do Século XX , História do Século XXI , HumanosRESUMO
Vaishnavi Ananthanarayanan investigates the regulation of motor proteins and cytoskeleton-organelle interactions using single-molecule microscopy.
Assuntos
Biologia Celular/história , Ciência , Mulheres , História do Século XX , História do Século XXI , HumanosRESUMO
Nan Yan studies the physiological function of innate immune signaling in the absence of pathogen infection.
Assuntos
Imunidade Inata/imunologia , Transdução de Sinais/imunologia , Animais , Interações Hospedeiro-Patógeno/imunologia , HumanosRESUMO
Ye Tian investigates how mitochondrial stress signaling pathways regulate longevity using C. elegans as a model system.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Longevidade , Mitocôndrias/metabolismo , Animais , Modelos Biológicos , Estresse Oxidativo , Transdução de SinaisRESUMO
Gaia Pigino studies the molecular mechanisms and principles of self-organization in cilia using 3D cryo-EM.
Assuntos
Cílios/ultraestrutura , Microscopia Crioeletrônica/história , Rim/ultraestrutura , Pulmão/ultraestrutura , Academias e Institutos/história , Animais , Clorófitas/metabolismo , Clorófitas/ultraestrutura , Cílios/metabolismo , Microscopia Crioeletrônica/métodos , Flagelos/metabolismo , Flagelos/ultraestrutura , História do Século XX , História do Século XXI , Humanos , Itália , Rim/metabolismo , Pulmão/metabolismoRESUMO
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.
