Genomes and Genes
Richard A Flavell
Affiliation: Yale University
- Song Y, Rongvaux A, Taylor A, Jiang T, Tebaldi T, Balasubramanian K, et al. A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies. Nat Commun. 2019;10:366 pubmed publisher..Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research. ..
- Jackson R, Kroehling L, Khitun A, Bailis W, Jarret A, York A, et al. The translation of non-canonical open reading frames controls mucosal immunity. Nature. 2018;: pubmed publisher..We therefore propose that the misannotation of non-canonical ORF-containing genes as non-coding RNAs may obscure the essential role of a multitude of previously undiscovered protein-coding genes in immunity and disease. ..
- Tong J, Flavell R, Li H. RNA m6A modification and its function in diseases. Front Med. 2018;12:481-489 pubmed publisher..In this review, we summarize the recent advances in m6A research and highlight the functional relevance and importance of m6A modification in in vitro cell lines, in physiological contexts, and in cancers. ..
- Palm N, de Zoete M, Cullen T, Barry N, Stefanowski J, Hao L, et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell. 2014;158:1000-1010 pubmed publisher..Thus, our studies suggest that IgA coating identifies inflammatory commensals that preferentially drive intestinal disease. Targeted elimination of such bacteria may reduce, reverse, or even prevent disease development. ..
- Li H, Jin C, Chen Y, Flavell R. Inflammasome activation and metabolic disease progression. Cytokine Growth Factor Rev. 2014;25:699-706 pubmed publisher..Here we review recent evidence that demonstrates the important roles of NLRs and inflammasomes in response to metabolic stress in different tissues. ..
- Rongvaux A, Jackson R, Harman C, Li T, West A, de Zoete M, et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell. 2014;159:1563-77 pubmed publisher..This mechanism provides a dual control, which determines whether mitochondria initiate an immunologically silent or a proinflammatory type of cell death. ..
- Herndler Brandstetter D, Ishigame H, Shinnakasu R, Plajer V, Stecher C, Zhao J, et al. KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity. Immunity. 2018;48:716-729.e8 pubmed publisher..Our work demonstrates that developmental plasticity of KLRG1+ effector CD8+ T cells is important in promoting functionally versatile memory cells and long-term protective immunity. ..
- Kim L, Morita R, Kobayashi Y, Eisenbarth S, Lee C, Elias J, et al. AMCase is a crucial regulator of type 2 immune responses to inhaled house dust mites. Proc Natl Acad Sci U S A. 2015;112:E2891-9 pubmed publisher..These data suggest that AMCase is a crucial regulator of type 2 immune responses to inhaled chitin-containing aeroallergens. ..
- Roulis M, Flavell R. Fibroblasts and myofibroblasts of the intestinal lamina propria in physiology and disease. Differentiation. 2016;92:116-131 pubmed publisher..We emphasize studies addressing the function of intestinal mesenchymal cells in vivo, and also discuss major open questions and current challenges in this field. ..
- Emgård J, Kammoun H, García Cassani B, Chesne J, Parigi S, Jacob J, et al. Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation. Immunity. 2018;48:120-132.e8 pubmed publisher..Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. ..
- Hu B, Jin C, Li H, Tong J, Ouyang X, Cetinbas N, et al. The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science. 2016;354:765-768 pubmed..Mechanistically, we found that AIM2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. Our results suggest that AIM2 may be a new therapeutic target for ionizing radiation exposure. ..
- Błażejewski A, Thiemann S, Schenk A, Pils M, Gálvez E, Roy U, et al. Microbiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation. Cell Rep. 2017;19:2319-2330 pubmed publisher..These data show that canonical inflammasome activation controls caspase-1 activity, contributing to exacerbation of chemical-induced colitis. ..
- Hwang S, Kim L, Lee G, Flavell R. Role of OCT-1 and partner proteins in T cell differentiation. Biochim Biophys Acta. 2016;1859:825-31 pubmed publisher..In this review, we will describe the role of OCT-1 in CD4 T cell differentiation and discuss how this factor orchestrates the fate and function of CD4 effector T cells. ..
- Cao G, Li H, Yin Z, Flavell R. Recent advances in dynamic m6A RNA modification. Open Biol. 2016;6:160003 pubmed publisher..Moreover, we emphasize recent advances of biological functions of m(6)A and conceive the possible roles of m(6)A in the regulation of immune response and related diseases. ..
- Fazzari P, Penachioni J, Gianola S, Rossi F, Eickholt B, Maina F, et al. Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis. BMC Dev Biol. 2007;7:55 pubmed..We infer that PlexinB1 plays a redundant role in mouse development and it is not strictly required for tumour induced angiogenesis. ..
- Chaiyachati B, Kaundal R, Zhao J, Wu J, Flavell R, Chi T. LoxP-FRT Trap (LOFT): a simple and flexible system for conventional and reversible gene targeting. BMC Biol. 2012;10:96 pubmed publisher..LOFT combines well-established basic genetic methods into a simple and reliable method for reversible gene targeting, with the flexibility of achieving traditional constitutive and conditional KO. ..
- Yu H, Gagliani N, Ishigame H, Huber S, Zhu S, Esplugues E, et al. Intestinal type 1 regulatory T cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes development. Proc Natl Acad Sci U S A. 2017;114:10443-10448 pubmed publisher..Therefore, modulating gut-associated lymphoid tissue to boost Tr1 cells may be important in type 1 diabetes management. ..
- Zhang Y, Nguyen T, Tang P, Kennedy N, Jiao H, Zhang M, et al. Regulation of Adipose Tissue Inflammation and Insulin Resistance by MAPK Phosphatase 5. J Biol Chem. 2015;290:14875-83 pubmed publisher..Deficiency of MKP5 resulted in increased inflammatory activation in macrophages. These findings thus demonstrate that MKP5 critically controls inflammation in white adipose tissue and the development of metabolic disorders. ..
- Herndler Brandstetter D, Shan L, Yao Y, Stecher C, Plajer V, Lietzenmayer M, et al. Humanized mouse model supports development, function, and tissue residency of human natural killer cells. Proc Natl Acad Sci U S A. 2017;114:E9626-E9634 pubmed publisher..Our humanized mouse model may thus be useful for preclinical testing of novel human NK cell-targeted and combinatory cancer immunotherapies and for studying how they elicit human antitumor immune responses in vivo. ..
- Zorca C, Kim L, Kim Y, Krause M, Zenklusen D, Spilianakis C, et al. Myosin VI regulates gene pairing and transcriptional pause release in T cells. Proc Natl Acad Sci U S A. 2015;112:E1587-93 pubmed publisher..We propose that homologous pairing and myosin VI-mediated transcriptional pause release account for the rapid and efficient expression of genes induced by an external stimulus. ..
- Kim L, Esplugues E, Zorca C, Parisi F, Kluger Y, Kim T, et al. Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells. Mol Cell. 2014;54:56-66 pubmed publisher..Finally, defects in the association lead to enhanced IL-17 induction. Collectively, our data indicate Th17 lineage differentiation is restrained by the Th2 locus via interchromosomal associations organized by Oct-1 and CTCF. ..
- Laouar Y, Crispe I, Flavell R. Overexpression of IL-7R alpha provides a competitive advantage during early T-cell development. Blood. 2004;103:1985-94 pubmed..This advantage occurred at early stages of T-cell development. Our findings support the model that overexpression of growth factor receptors can contribute to proliferation and malignancy...
- Mowel W, McCright S, Kotzin J, Collet M, Uyar A, Chen X, et al. Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA. Immunity. 2017;47:435-449.e8 pubmed publisher..Thus, non-coding elements responsive to extracellular cues unique to each ILC subset represent a key regulatory layer for controlling the identity and function of ILCs. ..
- Nowarski R, Jackson R, Gagliani N, de Zoete M, Palm N, Bailis W, et al. Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis. Cell. 2015;163:1444-56 pubmed publisher..IL-18 inhibited goblet cell maturation by regulating the transcriptional program instructing goblet cell development. These results inform on the mechanism of goblet cell dysfunction that underlies the pathology of ulcerative colitis. ..
- Williams A, Henao Mejia J, Harman C, Flavell R. miR-181 and metabolic regulation in the immune system. Cold Spring Harb Symp Quant Biol. 2013;78:223-30 pubmed publisher..We propose that these miRNAs will form a network to finely tune cellular metabolic status and that miR-181 will function as the primary metabolic rheostat of this network. ..
- Flavell R, Sanjabi S, Wrzesinski S, Licona Limón P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol. 2010;10:554-67 pubmed publisher..An overview of the current drugs and reagents available for inhibiting TGFbeta-induced signalling and their phase in clinical development is also provided. ..