Research Topics
Genomes and Genes
| Anjana RaoSummaryAffiliation: Harvard University Country: USA Publications
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Publications
A common factor regulates both Th1- and Th2-specific cytokine gene expressionJ W Rooney
Department of Genetics, Harvard Medical School, Boston, MA 02115
EMBO J 13:625-33. 1994..We propose that NF-ATp is a common regulatory factor for both Th1 and Th2 cytokine genes, and that the involvement of PKC-dependent factors, such as AP-1, may help determine Th1-/Th2-specific patterns of gene expression...
Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genesC Luo
Division of Cellular and Molecular Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell Biol 16:3955-66. 1996....
Calcium signaling in lymphocytesMasatsugu Oh-hora
Department of Pathology, Harvard Medical School, Immune Disease Institute, Boston, MA 02115, USA
Curr Opin Immunol 20:250-8. 2008..This review focuses on the signaling pathways upstream and downstream of Ca(2+) influx (the STIM/ORAI and calcineurin/NFAT pathways, respectively)...
Transcription factors of the NFAT family: regulation and functionA Rao
Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
Annu Rev Immunol 15:707-47. 1997....
Modulation of chromatin structure regulates cytokine gene expression during T cell differentiationS Agarwal
Department of Pathology, Harvard Medical School, Center for Blood Research, Boston, Massachusetts 02115, USA
Immunity 9:765-75. 1998..We propose that chromatin remodeling of cytokine gene loci is functionally associated with productive T cell differentiation and may explain the coordinate regulation of Th2 cytokine genes...
New functions for DNA binding domainsA Rao
Center for Blood Research and the Department of Pathology, Harvard Medical School, Warren Alpert Building, 200 Longwood Avenue, Boston, MA 02115, USA
Sci STKE 2001:pe1. 2001..This change in structure may influence the binding of activators or repressors of transcription, thus allowing a single transcription factor to have two different activities...
Role of NFAT proteins in IL13 gene transcription in mast cellsSilvia Monticelli
Department of Pathology, Harvard Medical School, and CBR Institute for Biomedical Research, Boston, MA 02115, USA
J Biol Chem 279:36210-8. 2004..We suggest that mast cells lack a co-activator protein that stabilizes the binding of NFAT2 to the IL13 promoter by interacting either with NFAT2 itself or with a DNA-bound complex of NFAT2 and GATA proteins...
Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunityK Mark Ansel
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
Nat Immunol 5:1251-9. 2004....
Hair loss and defective T- and B-cell function in mice lacking ORAI1Yousang Gwack
Department of Pathology, Harvard Medical School and the Immune Disease Institute, Rm 152, Warren Alpert Bldg, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Mol Cell Biol 28:5209-22. 2008....
Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLsFernando Cruz-Guilloty
Harvard Medical School and the Immune Disease Institute, Boston, MA 02115, USA
J Exp Med 206:51-9. 2009..Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs...
Hyperactivation of nuclear factor of activated T cells 1 (NFAT1) in T cells attenuates severity of murine autoimmune encephalomyelitisSrimoyee Ghosh
Department of Pathology, Harvard Medical School and Immune Disease Institute, Children s Hospital, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 107:15169-74. 2010....
Requirement for balanced Ca/NFAT signaling in hematopoietic and embryonic developmentMartin R Muller
Department of Pathology and Immune Disease Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 106:7034-9. 2009....
Regulation of the germinal center response by microRNA-155To Ha Thai
CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
Science 316:604-8. 2007..miR-155 exerts this control, at least in part, by regulating cytokine production. These results also suggest that individual microRNAs can exert critical control over mammalian differentiation processes in vivo...
Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cellsMatthew E Pipkin
Harvard Medical School, Boston, MA 02115, USA Immune Disease Institute, Boston, MA 02115, USA
Immunity 32:79-90. 2010..Thus, inflammation influences both effector and memory CTL differentiation, whereas persistent IL-2 stimulation promotes effector at the expense of memory CTL development...
Molecular analysis of a locus control region in the T helper 2 cytokine gene cluster: a target for STAT6 but not GATA3Dong U Lee
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 101:16010-5. 2004..We suggest that the RAD50 LCR has a complex and dual role in Th1 and Th2 differentiation, communicating early T cell antigen receptor and cytokine signals to the IL-4/IL-13 locus in both differentiating cell types...
A 10-aa-long sequence in SLP-76 upstream of the Gads binding site is essential for T cell development and functionLalit Kumar
Division of Immunology, Children s Hospital, CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 102:19063-8. 2005..These results indicate that the Lck binding region of SLP-76 is essential for T cell antigen receptor signaling and normal T cell development and function...
A mutation in Orai1 causes immune deficiency by abrogating CRAC channel functionStefan Feske
The CBR Institute for Biomedical Research, and the Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
Nature 441:179-85. 2006..We propose that Orai1 is an essential component or regulator of the CRAC channel complex...
Biochemical and functional characterization of Orai proteinsYousang Gwack
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
J Biol Chem 282:16232-43. 2007..Together, these data establish Orai1 as a predominant mediator of store-operated calcium entry, proliferation, and cytokine production in T cells...
A 3' enhancer in the IL-4 gene regulates cytokine production by Th2 cells and mast cellsDeborah C Solymar
The Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Immunity 17:41-50. 2002..These results identify an essential enhancer which regulates IL-4 gene expression in two important cell lineages in vivo...
Involvement of NFAT1 in B cell self-toleranceRobert A Barrington
CBR Institute for Biomedical Research, Harvard University, Boston, MA 02115, USA
J Immunol 177:1510-5. 2006..Taken together, these studies provide direct evidence that the transcription factor NFAT1 is involved in B cell anergy...
A molecular dissection of lymphocyte unresponsiveness induced by sustained calcium signallingVigo Heissmeyer
Department of Pathology, Harvard Medical School, CBR Institute for Biomedical Research, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
Novartis Found Symp 267:165-74; discussion 174-9. 2005..Thus Ca(2+)-calcineurin-NFAT signalling links gene transcription to a multi-step programme that leads to impaired signal transduction in anergic T cells...
Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation responseMark S Sundrud
Department of Pathology, Harvard Medical School and Immune Disease Institute, Boston, MA 02115, USA
Science 324:1334-8. 2009..These results indicate that the AAR pathway is a potent and selective regulator of inflammatory T cell differentiation in vivo...
A distal enhancer in the interferon-gamma (IFN-gamma) locus revealed by genome sequence comparisonDong U Lee
Center for Blood Research and the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 279:4802-10. 2004..Together, these findings identify a highly conserved distal enhancer in the IFN-gamma cytokine locus and validate our approach as a successful method to detect cis-regulatory elements...
Signalling to transcription: store-operated Ca2+ entry and NFAT activation in lymphocytesYousang Gwack
Department of Pathology, Harvard Medical School, The CBR Institute for Biomedical Research, 200 Longwood Avenue, Boston, MA 02115, USA
Cell Calcium 42:145-56. 2007..These approaches, together with subsequent mutational and electrophysiological analyses, converged to identify human Orai1 as a pore subunit of the CRAC channel and as the gene product mutated in the SCID patients...
Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteinsVigo Heissmeyer
Center for Blood Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Nat Immunol 5:255-65. 2004..Our results define a complex molecular program that links gene transcription induced by calcium and calcineurin to a paradoxical impairment of signal transduction in anergic T cells...
Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complexSonia Sharma
Department of Pathology, Harvard Medical School, Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital Boston, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 108:11381-6. 2011....
Chromatin-based regulation of cytokine transcription in Th2 cells and mast cellsSilvia Monticelli
Department of Pathology, Harvard Medical School, and CBR Institute for Biomedical Research, Boston, MA 02115, USA
Int Immunol 17:1513-24. 2005....
Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and toleranceMasatsugu Oh-hora
Harvard Medical School and Immune Disease Institute, Boston, Massachusetts 02115, USA
Nat Immunol 9:432-43. 2008..We conclude that both STIM1 and STIM2 promote store-operated Ca2+ entry into T cells and fibroblasts and that STIM proteins are required for the development and function of regulatory T cells...
Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cellsKian Peng Koh
Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital Boston, Boston, MA 02115, USA
Cell Stem Cell 8:200-13. 2011..Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs...
Regulation of Th2 differentiation and Il4 locus accessibilityK Mark Ansel
Harvard Medical School, CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
Annu Rev Immunol 24:607-56. 2006....
A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFATYousang Gwack
The CBR Institute for Biomedical Research and the Departments of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
Nature 441:646-50. 2006..Thus, genetic screening in Drosophila can be successfully applied to cross evolutionary boundaries and identify new regulators of a transcription factor that is expressed only in vertebrates...
T(H) cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genesOrly Avni
The Center for Blood Research and the Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Nat Immunol 3:643-51. 2002....
A conserved docking motif for CK1 binding controls the nuclear localization of NFAT1Heidi Okamura
CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell Biol 24:4184-95. 2004..The CK1 docking motif is present in proteins of the Wnt, Hedgehog, and circadian-rhythm pathways, which also integrate the activities of CK1 and GSK3...
Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cellsIvana M Djuretic
Harvard Medical School and the CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
Nat Immunol 8:145-53. 2007..Our data indicate that cytokine gene expression in T(H)1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing...
Regulation of interferon-gamma gene expression by nuclear factor of activated T cellsA Kiani
Department of Pathology, Harvard Medical School, and the Center for Blood Research, Boston, MA 02115, USA
Blood 98:1480-8. 2001..These results suggest that IFN-gamma production by T cells is regulated by NFAT1, most likely at the level of gene transcription...
Structural delineation of the calcineurin-NFAT interaction and its parallels to PP1 targeting interactionsHuiming Li
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
J Mol Biol 342:1659-74. 2004....
Aberrant T cell differentiation in the absence of DicerStefan A Muljo
The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 202:261-9. 2005..Independent of their proliferation defect, Dicer-deficient helper T cells preferentially expressed interferon-gamma, the hallmark effector cytokine of the Th1 lineage...
Structure of calcineurin in complex with PVIVIT peptide: portrait of a low-affinity signalling interactionHuiming Li
The CBR Institute, for Biomedical Research, 200 Longwood Avenue, Boston, MA 02115, USA
J Mol Biol 369:1296-306. 2007....
STIM1 gates the store-operated calcium channel ORAI1 in vitroYubin Zhou
Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital, Boston, Massachusetts, USA
Nat Struct Mol Biol 17:112-6. 2010....
Immunological applications of genomicsSilvia Monticelli
Harvard Medical School and the CBR Institute for Biomedical Research, Boston, MA 02115, USA
Genome Biol 7:321. 2006..A report of the Cold Spring Harbor Laboratory meeting 'Gene Expression and Signaling in the Immune System', Cold Spring Harbor, New York, USA, 26-30 April 2006...
NFAT1 and NFAT2 are positive regulators of IL-4 gene transcriptionSilvia Monticelli
Department of Pathology, Harvard Medical School, and the Center for Blood Research, Alpert Building Rm 152, 200 Longwood Avenue, Boston, MA 02115, USA
Eur J Immunol 32:2971-8. 2002....
Pore architecture of the ORAI1 store-operated calcium channelYubin Zhou
Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital Boston, 200 Longwood Avenue, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 107:4896-901. 2010..The cross-linking data further identify a relatively rigid segment of TM1 adjacent to E106 that is likely to contribute to the selectivity filter...
Transcriptional complexes formed by NFAT dimers regulate the induction of T cell toleranceNoemi Soto-Nieves
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
J Exp Med 206:867-76. 2009..These data also establish a basis for the design of immunomodulatory strategies that specifically target each type of complex...
Orphans against autoimmunityHozefa Bandukwala
Department of Pathology, Harvard Medical School and Immune Disease Institute, 200 Longwood Avenue, Boston, MA 02115, USA
Immunity 29:167-8. 2008..In this issue of Immunity, Hermann-Kleiter et al. (2008) identify a nuclear orphan receptor, NR2F6, as a negative regulator of the T helper 17 cell subset and report that NR2F6-deficient mice develop late-onset autoimmune disease...
Foxp1 is an essential transcriptional regulator of B cell developmentHui Hu
Department of Pathology, Harvard Medical School, CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
Nat Immunol 7:819-26. 2006..Our results identify Foxp1 as an essential participant in the transcriptional regulatory network of B lymphopoiesis...
Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivoS Agarwal
Department of Pathology, Harvard Medical School and The Center for Blood Research, Boston, Massachusetts 02115, USA
Immunity 12:643-52. 2000..This restricted access enables antigen-dependent and subset-specific transcription of cytokine genes...
Normal peripheral T-cell function in c-Fos-deficient miceJ Jain
Division of Tumor Virology, Dana Farber Cancer Institute, Boston, Massachusetts 02115
Mol Cell Biol 14:1566-74. 1994..Our results suggest that other Fos family members may be capable of substituting functionally for c-Fos during T-cell development and cytokine gene transcription in activated T cells...
Transcriptional mechanisms underlying lymphocyte toleranceFernando Macian
Center for Blood Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Cell 109:719-31. 2002..Thus, in the absence of AP-1, NFAT imposes a genetic program of lymphocyte anergy that counters the program of productive activation mediated by the cooperative NFAT:AP-1 complex...
Bioinformatics for the 'bench biologist': how to find regulatory regions in genomic DNAJulie Nardone
Department of Pathology, Harvard Medical School and the CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
Nat Immunol 5:768-74. 2004....
Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 geneDong U Lee
Department of Pathology, Harvard Medical School and The Center for Blood Research, Boston, MA 02115, USA
Immunity 16:649-60. 2002..5' demethylation is not required for chromatin remodeling or primary transcription of the IL-4 gene but is strongly associated with efficient, high-level induction of IL-4 transcripts by differentiated Th2 cells...
The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardationMamta Tahiliani
Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine and BCMP, Brigham and Women s Hospital and Harvard Medical School, 221 Longwood Avenue Boston, Massachusetts 02115, USA
Nature 447:601-5. 2007..We propose that loss of SMCX activity impairs REST-mediated neuronal gene regulation, thereby contributing to SMCX-associated X-linked mental retardation...
Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2Myunggon Ko
Department of Pathology, Harvard Medical School, Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital Boston, Boston, Massachusetts 02115, USA
Nature 468:839-43. 2010..Measurement of 5hmC levels in myeloid malignancies may prove valuable as a diagnostic and prognostic tool, to tailor therapies and assess responses to anticancer drugs...
Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cellsWilliam A Pastor
Harvard Medical School, Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital Boston, Boston, Massachusetts 02115, USA
Nature 473:394-7. 2011..Our results indicate that 5hmC has a probable role in transcriptional regulation, and suggest a model in which 5hmC contributes to the 'poised' chromatin signature found at developmentally-regulated genes in ES cells...
TID1, a mammalian homologue of the drosophila tumor suppressor lethal(2) tumorous imaginal discs, regulates activation-induced cell death in Th2 cellsJosh Syken
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, D2 544A, Boston, MA 02115 5701, USA
Oncogene 22:4636-41. 2003..Hence, the accumulation of Tid-1S in Th2 cells following activation represents a novel mechanism that may contribute to the induction of apoptosis resistance during the activation of Th2 cells...
Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1Mamta Tahiliani
Department of Pathology, Harvard Medical School and Immune Disease Institute, 200 Longwood Avenue, Boston, MA 02115, USA
Science 324:930-5. 2009..hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference-mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC...
Regulation of gene expression in mast cells: micro-rNA expression and chromatin structural analysis of cytokine genesSilvia Monticelli
Department of Pathology, Harvard Medical School, and CBR Institute for Biomedical Research, Boston, MA 02115, USA
Novartis Found Symp 271:179-87; discussion 187-90, 198-9. 2005..We are studying the biological functions of selected miRNAs...
Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNPLLShalini Oberdoerffer
Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA
Science 321:686-91. 2008..Induction of hnRNPLL during hematopoietic cell activation and differentiation may allow cells to rapidly shift their transcriptomes to favor proliferation and inhibit cell death...
Transcriptional regulation by calcium, calcineurin, and NFATPatrick G Hogan
The Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
Genes Dev 17:2205-32. 2003
An epigenetic view of helper T cell differentiationK Mark Ansel
Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
Nat Immunol 4:616-23. 2003..Recent studies have begun to elucidate the molecular mechanisms that establish and maintain polarized cytokine gene expression, and thus the cellular identity of differentiated helper T cells...
Down-regulation of IL-4 gene transcription and control of Th2 cell differentiation by a mechanism involving NFAT1A Kiani
The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
Immunity 7:849-60. 1997..Consistent with this observation, NFAT1-/- mice are more susceptible to infection with Leishmania major. This report provides evidence that NFAT proteins regulate not only the initiation but also the termination of gene transcription...
Gene regulation mediated by calcium signals in T lymphocytesS Feske
Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Nat Immunol 2:316-24. 2001..We demonstrate an elaborate network of signaling pathways downstream of the T cell receptor, explaining the complexity of changes in gene expression during T cell activation...
Selective inhibition of NFAT activation by a peptide spanning the calcineurin targeting site of NFATJ Aramburu
Center for Blood Research, Harvard Medical School, Boston Massachusetts 02115, USA
Mol Cell 1:627-37. 1998..Thus, disruption of the enzyme-substrate docking interaction that directs calcineurin to NFAT can effectively block NFAT-dependent functions...
The transcription factor NFAT3 mediates neuronal survivalAlessandra B Benedito
Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 280:2818-25. 2005..Taken together, these results reveal an essential function for NFAT3-mediated transcription in neuronal survival that may play important roles in the developing and mature brain...
Domain requirements and sequence specificity of DNA binding for the forkhead transcription factor FOXP3Kian Peng Koh
Department of Pathology, Harvard Medical School and Immune Disease Institute, Boston, Massachusetts, United States of America
PLoS ONE 4:e8109. 2009..These results establish a practical framework for understanding the molecular basis by which FOXP3 regulates gene transcription and programs Treg suppressive function...
New twists of T cell fate: control of T cell activation and tolerance by TGF-beta and NFATMark S Sundrud
Department of Pathology, Harvard Medical School, and The CBR Institute for Biomedical Research Inc, Boston, MA 02115, USA
Curr Opin Immunol 19:287-93. 2007..Recent findings have begun to shed light on the mechanisms by which TGF-beta and NFAT integrate multiple signaling inputs to determine the direction of naïve T-cell differentiation...
Transcriptional basis of lymphocyte toleranceMadhuri Borde
The CBR Institute for Biomedical Research and the Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Immunol Rev 210:105-19. 2006....
A CD8 T cell-intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivoThomas Fehr
Transplantation Biology Research Center, Massachusetts General Hospital Harvard Medical School, Boston, MA, USA
Blood 115:1280-7. 2010..Thus, our study reveals a CD8 T cell-intrinsic NFAT1 requirement for CD8 tolerance in vivo...
Ca2+/calcineurin signalling in cells of the immune systemStefan Feske
Department of Pathology, Harvard Medical School, Boston and The CBR Institute for Biomedical Research, 200 Longwood Ave, Boston, MA 02115, USA
Biochem Biophys Res Commun 311:1117-32. 2003..This review focuses on recent studies elucidating the role of Ca(2+)/calcineurin signalling of the immune system...
NFAT5 binds to the TNF promoter distinctly from NFATp, c, 3 and 4, and activates TNF transcription during hypertonic stress aloneJonathan H Esensten
CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School 800 Huntington Avenue, Boston, MA 02115, USA
Nucleic Acids Res 33:3845-54. 2005....
Reciprocal modulatory interaction between human immunodeficiency virus type 1 Tat and transcription factor NFAT1F Macian
Department of Pathology, Harvard Medical School, and Center for Blood Research, Boston, Massachusetts 02115, USA
Mol Cell Biol 19:3645-53. 1999..We discuss the potentially opposing roles of NFAT1 and another family member, NFAT2, in regulating gene transcription of HIV-1 and endogenous cytokine genes...
The behaviour of 5-hydroxymethylcytosine in bisulfite sequencingYun Huang
Department of Pathology, Harvard Medical School and Immune Disease Institute, Boston, Massachusetts, United States of America
PLoS ONE 5:e8888. 2010..Since 5-hmC reacts with bisulfite to yield cytosine 5-methylenesulfonate (CMS), we asked how DNA containing 5-hmC behaves in bisulfite sequencing...
Partners in transcription: NFAT and AP-1F Macian
Department of Pathology, Harvard Medical School and The Center for Blood Research, 200 Longwood Avenue, Boston, Massachusetts, MA 02115, USA
Oncogene 20:2476-89. 2001..Balanced activation of NFAT and AP-1 is known to be required for productive immune responses, but the role of NFAT:AP-1 interactions in other cell types and biological processes remains to be understood...
Regulation of allergic inflammation and eosinophil recruitment in mice lacking the transcription factor NFAT1: role of interleukin-4 (IL-4) and IL-5J P Viola
Center for Blood Research and the Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Blood 91:2223-30. 1998..Thus, the presence of NFAT1 might inhibit the allergic response, perhaps by interfering with the development of Th2 immune responses, and the lack or dysfunction of NFAT1 could potentially underlie certain cases of atopic disease...
Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP)C Garcia-Rodriguez
Department of Pathology, Harvard Medical School, and the Center for Blood Research, Boston, Massachusetts 02115, USA
J Exp Med 187:2031-6. 1998..Recruitment of the coactivators p300/CBP by the transactivation domains of NFAT proteins is likely to play a critical role in NFAT-dependent gene expression during the immune response...
Bridging the NFAT and NF-kappaB families: NFAT5 dimerization regulates cytokine gene transcription in response to osmotic stressC Lopez-Rodriguez
The Center for Blood Research and, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Immunity 15:47-58. 2001..We suggest that NFAT5 participates in specific aspects of host defense by upregulating TNF family genes and other target genes in T cells...
Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activityH Okamura
The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell 6:539-50. 2000..This conformational switch paradigm may explain modification-induced functional changes in other heavily phosphorylated proteins...
MicroRNA profiling of the murine hematopoietic systemSilvia Monticelli
Department of Pathology, Harvard Medical School, and CBR Institute for Biomedical Research, Boston, MA 02115, USA
Genome Biol 6:R71. 2005..It is becoming clear that miRNAs play an important role in the regulation of gene expression during development. However, in mammals, expression data are principally based on whole tissue analysis and are still very incomplete...
Gene regulation and signal transduction in the immune systemTiffany Horng
Department of Pathology, Harvard Medical School, Immune Disease Institute, Boston, Massachusetts 02115, USA
Genome Biol 9:315. 2008..A report of the meeting 'Gene Expression and Signaling in the Immune System', Cold Spring Harbor, USA, 22-26 April 2008...
Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expressionCristina Lopez-Rodriguez
Department of Pathology, Harvard Medical School and Center for Blood Research, Institute for Biomedical Research, 200 Longwood Avenue, Boston MA 02115, USA
Proc Natl Acad Sci U S A 101:2392-7. 2004..Our findings demonstrate a central role for NFAT5 as a tonicity-responsive transcription factor required for kidney homeostasis and function...
Introduction to COI volume on lymphocyte activation 2008Anjana Rao
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Immune Disease Institute, Room 152, Warren Alpert Building, 200 Longwood Avenue, Boston, MA 02115, USA
Curr Opin Immunol 20:247-9. 2008
Efficiency of RNA interference in the mouse hematopoietic system varies between cell types and developmental stagesPhilipp Oberdoerffer
The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
Mol Cell Biol 25:3896-905. 2005..The extent of gene inactivation varies between different cell types and is least efficient in mature lymphocytes. Our data suggest that RNAi is affected by factors beyond small interfering RNA-mRNA stoichiometry...
Dissecting ICRAC, a store-operated calcium currentPatrick G Hogan
The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Trends Biochem Sci 32:235-45. 2007....
Molecular basis of calcium signaling in lymphocytes: STIM and ORAIPatrick G Hogan
Department of Pathology, Harvard Medical School, Immune Disease Institute, Children s Hospital Boston, Massachusetts 02115, USA
Annu Rev Immunol 28:491-533. 2010..In this review, we discuss selected aspects of Ca(2+) signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store-operated Ca(2+) entry...
Integration of TCR and IL-4 signals through STAT6 and the regulation of IL-4 gene expressionC B Schmidt-Weber
Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Mol Immunol 37:767-74. 2000..Calcineurin-mediated serine dephosphorylation of STAT6 and STAT6 serine phosphorylation may counter-regulate transcriptional activity of STAT6...
Long-range transcriptional regulation of cytokine gene expressionS Agarwal
Center for Blood Research, Boston, MA 02115, USA
Curr Opin Immunol 10:345-52. 1998..These studies have begun to elucidate the basis for cell-specificity and high-level expression of cytokine genes...
NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and JunC Lopez-Rodriguez
Department of Pathology, Harvard Medical School, The Center for Blood Research, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 96:7214-9. 1999....
Impaired NFAT regulation and its role in a severe combined immunodeficiencyS Feske
The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
Immunobiology 202:134-50. 2000....
T cell differentiation: a mechanistic viewO Avni
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Curr Opin Immunol 12:654-9. 2000..These changes require the coordinate actions of antigen- and cytokine-induced transcription factors, chromatin remodeling complexes, histone-modifying enzymes and subset-specific transcription factors...
NF-AT5: the NF-AT family of transcription factors expands in a new directionC Lopez-Rodriguez
Center for Blood Research and the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
Cold Spring Harb Symp Quant Biol 64:517-26. 1999
Transcriptional regulation in lymphocytesH Okamura
Department of Pathology, Harvard Medical School and The Center for Blood Research, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
Curr Opin Cell Biol 13:239-43. 2001..The emerging theme is one of cell-type-specific regulation, affecting not only the functional activation of transcription factors but also their access to appropriate regions of DNA...
Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK complexM Kobori
Department of Cell Biology, Harvard Medical School, Boston, MA, USA
Cell Death Differ 11:123-30. 2004..We demonstrate that wedelolactone is an inhibitor of IKK, a kinase critical for activation of NF-kappaB by mediating phosphorylation and degradation of IkappaBalpha...
Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNAL Chen
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Nature 392:42-8. 1998..The tight association of the three proteins on DNA creates a continuous groove for the recognition of 15 base pairs...
Regulation of gene expression in peripheral T cells by Runx transcription factorsIvana M Djuretic
Department of Pathology, Harvard Medical School and Immune Disease Institute and Program in Cellular and Molecular Medicine, Children s Hospital Boston, Boston, Massachusetts, USA
Adv Immunol 104:1-23. 2009..Here, we review gene regulation by Runx proteins in T lymphocytes, with a focus on their recently emerging roles in the development and function of peripheral CD4+ and CD8+ T lineages...
A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patientsStefan Feske
CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 202:651-62. 2005..They also offer evidence for a functional link between CRAC and Kv1.3 channels, and establish a model system for molecular genetic studies of the CRAC channel...
The role of NFAT transcription factors in integrin-mediated carcinoma invasionSebastien Jauliac
Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, 200 Longwood Avenue, Boston MA 02115, USA
Nat Cell Biol 4:540-4. 2002..These observations show that NFATs are targets of alpha(6)beta(4) integrin signalling and are involved in promoting carcinoma invasion, highlighting a novel function for this family of transcription factors in human cancer...
Normal function of the transcription factor NFAT1 in wasted mice. Chromosome localization of NFAT1 geneC Luo
Division of Cellular and Molecular Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Gene 180:29-36. 1996..Therefore, the wasted phenotype is not due to a defect in the expression or early regulation of the NFAT1 protein...
Expression of the transcription factor NFATp in a neuronal cell line and in the murine nervous systemA M Ho
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts
J Biol Chem 269:28181-6. 1994..The presence of NFATp in the nervous system suggests that it has a role in the transcription of specific neuronal genes in response to increases in cytosolic calcium...
A similar DNA-binding motif in NFAT family proteins and the Rel homology regionJ Jain
Dana Farber Cancer Institute, Department of Pathology, Boston, Massachusetts 02115
J Biol Chem 270:4138-45. 1995..The results suggest that NFATp and Rel family proteins bind to DNA using similar structural motifs...
An asymmetric NFAT1 dimer on a pseudo-palindromic kappa B-like DNA siteLei Jin
Department of Biological Chemistry and Molecular Pharmacology and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Nat Struct Biol 10:807-11. 2003..The structure we have determined may correspond to a functional NFAT binding mode at palindromic sites of genes induced during the anergic response to weak TCR signaling...
ORAI1 deficiency and lack of store-operated Ca2+ entry cause immunodeficiency, myopathy, and ectodermal dysplasiaChristie Ann McCarl
Department of Pathology, New York University, Langone Medical Center, New York, NY 10016, USA
J Allergy Clin Immunol 124:1311-1318.e7. 2009..T-cell activation requires Ca2+ influx through Ca2+-release activated Ca2+ (CRAC) channels encoded by the gene ORAI1...
Selective inhibition of calcineurin-NFAT signaling by blocking protein-protein interaction with small organic moleculesMichael H A Roehrl
Department of Biological Chemistry, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 101:7554-9. 2004....
Research Grants
- CAPACITATIVE CALCIUM ENTRY DEFECT IN IMMUNE DEFICIENCYAnjana Rao; Fiscal Year: 2002..Deletion mapping using spectral karyotyping and microsatellite markers will be used to further narrow down the chromosomal region involved in the defect and candidate genes in this region will be evaluated. ..
- Manipulation of T cell tolerance with small organic mol*Anjana Rao; Fiscal Year: 2005..The hope is that the 'information obtained from this pilot R21 proposal will eventually be extended to whole animal models of transplant and tumour rejection, allergy and autoimmune disease. ..
- Role of micro-RNAs in T cells and other immune/haematopoietic cellsAnjana Rao; Fiscal Year: 2007..Together these studies should greatly increase our understanding of the role of miRNAs in T cells and other cells of the immune and hematopoietic systems. ..
