Research Topics
Genomes and Genes
| Xi HeSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the wayXi He
Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
Development 131:1663-77. 2004..We also discuss the regulation of Lrp5/Lrp6 by other extracellular ligands, and LRP5 mutations associated with familial osteoporosis and other disorders...
DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradationMikhail V Semenov
F M Kirby Neurobiology Center, Children s Hospital Boston and Department of Neurology, Harvard Medical School, 61 Binney Street, Boston, MA 02115, USA
J Biol Chem 283:21427-32. 2008..7 h) of LRP6. We conclude that DKK1 inhibition of LRP6 is independent of LRP6 internalization and degradation...- A WNTer wonderland in SnowbirdXi He
Neurobiology Program, Children s Hospital and Harvard Medical School, Boston, MA 02115 5724, USA
Development 133:2597-603. 2006.... - Unwinding a path to nuclear beta-cateninXi He
Program of Neurobiology, Children s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115 USA
Cell 127:40-2. 2006..Phosphorylated p68 dissociates beta-catenin from the Axin destruction complex, thereby promoting nuclear beta-catenin signaling independent of Wnt activation... - Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functionsXin Zeng
The F M Kirby Neurobiology Center, Children s Hospital Boston, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
Development 135:367-75. 2008..We discuss the dual roles of the axin-Gsk3 complex and signal amplification by Lrp6-axin interaction during Wnt/beta-catenin signaling... - SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitorMikhail Semenov
Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 280:26770-5. 2005..Our findings suggest that SOST is an antagonist for Wnt signaling and that the loss of SOST function likely leads to the hyperactivation of Wnt signaling that underlies bone overgrowth seen in sclerosteosis patients... - A mechanism for Wnt coreceptor activationKeiko Tamai
Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 13:149-56. 2004..Our study identifies a critical signaling module and a key phosphorylation-dependent activation step of the Wnt receptor complex and reveals a unifying logic for transmembrane signaling by Wnts, growth factors, and cytokines... - A dual-kinase mechanism for Wnt co-receptor phosphorylation and activationXin Zeng
Neurobiology Program, Children's Hospital Boston, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 438:873-7. 2005.... - Dissecting molecular differences between Wnt coreceptors LRP5 and LRP6Bryan T MacDonald
F M Kirby Neurobiology Center, Children s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS ONE 6:e23537. 2011..Our studies therefore uncover a new and important molecular tuning mechanism for differential regulation of LRP5 and LRP6 phosphorylation and signaling activity... - R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and beta-catenin signalingQiou Wei
Program of Neurobiology, Children s Hospital Boston, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 282:15903-11. 2007..Our study reveals interesting similarity and distinction between Wnt and R-spondin signaling... - Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6Bryan T MacDonald
F M Kirby Neurobiology Center, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 283:16115-23. 2008.... - Human ACF1 alters the remodeling strategy of SNF2hXi He
Department of Molecular Biology, Massachusetts General Hospital, Boston, USA
J Biol Chem 281:28636-47. 2006..Thus, we observed divergent remodeling behaviors in these two remodeling families and found that the manner in which hACF1 alters the remodeling behavior of the ATPase is not shared by SWI/SNF subunits... - Tiki1 is required for head formation via Wnt cleavage-oxidation and inactivationXinjun Zhang
The F M Kirby Neurobiology Center, Boston Children s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
Cell 149:1565-77. 2012..TIKI proteins may represent potential therapeutic targets... 
Diverse regulation of SNF2h chromatin remodeling by noncatalytic subunitsXi He
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Biochemistry 47:7025-33. 2008..We suggest that the ability to sense adjacent DNA is a general property of the binding partners of SNF2h and that each partner provides distinct regulation that contributes to distinct cellular function...- Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6Geng Wu
F M Kirby Neurobiology Center, Children s Hospital Boston, Harvard Medical School, Boston, MA, USA
PLoS ONE 4:e4926. 2009..This model provides a possible mechanism to account, in part, for inhibition of beta-catenin phosphorylation by Wnt-activated LRP6... - Presynaptic local signaling by a canonical wingless pathway regulates development of the Drosophila neuromuscular junctionClaudia Miech
F M Kirby Neurobiology Center, Children s Hospital, Boston, Massachusetts 02115, USA
J Neurosci 28:10875-84. 2008.... - Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanismChunming Liu
Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
Cell 108:837-47. 2002..Our study uncovers distinct roles and steps of beta-catenin phosphorylation, identifies CKIalpha as a component in Wnt/beta-catenin signaling, and has implications to pathogenesis/therapeutics of human cancers and diabetes... - Association of Dishevelled with the clathrin AP-2 adaptor is required for Frizzled endocytosis and planar cell polarity signalingAnan Yu
Department of Cell Biology and CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
Dev Cell 12:129-41. 2007..We suggest that the direct interaction of Dvl2 with AP-2 is important for Frizzled internalization and Frizzled/PCP signaling... - LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOSTMikhail V Semenov
Neurobiology Program, Children s Hospital Boston, 61 Binmney Street, Boston, MA 02115, USA
J Biol Chem 281:38276-84. 2006.... - Retinoic acid-inducible G protein-coupled receptors bind to frizzled receptors and may activate non-canonical Wnt signalingYuko Harada
Neurobiology Program, Children s Hospital Boston, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
Biochem Biophys Res Commun 358:968-75. 2007..In zebrafish embryo, XRAIG2 also causes Ca(2+) flux, one of the consequences of non-canonical Wnt signaling. These results suggest a possible crosstalk/integration between Wnt/Frizzled and RAIG signal transduction pathways... 
Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factorHans R Widlund
Department of Pediatric Oncology, Dana Farber Cancer Institute, Dana 630, 44 Binney Street, Boston, MA 02115, USA
J Cell Biol 158:1079-87. 2002..Thus, beta-catenin regulation of MITF expression represents a tissue-restricted pathway that significantly influences the growth and survival behavior of this notoriously treatment-resistant neoplasm...- Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1Jin Zhang
Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA 02111, USA
J Bone Miner Res 26:1953-63. 2011..miR-335-5p proves to be a potential and useful targeting molecule for promoting bone formation and regeneration... - Divergent human remodeling complexes remove nucleosomes from strong positioning sequencesChuong D Pham
Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA
Nucleic Acids Res 38:400-13. 2010..This suggests that remodeling complexes may share a conserved repositioning specificity, and that their divergent biological functions may largely arise from other properties conferred by complex-specific subunits... - Wnt/beta-catenin signaling: components, mechanisms, and diseasesBryan T MacDonald
F M Kirby Neurobiology Center, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
Dev Cell 17:9-26. 2009..Finally, we highlight some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis, and discuss potential therapeutic implications... - Wnt signaling went derailed again: a new track via the LIN-18 receptor?Xi He
Division of Neuroscience, Children s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
Cell 118:668-70. 2004..LIN-18/Ryk and LIN-17/Fz appear to exhibit distinct Wnt specificity, and surprisingly, the LIN-18 intracellular domain may be dispensable... - Ozz; a new name on the long list of beta-catenin's nemesesGeng Wu
Children's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 13:451-3. 2004..Ozz appears to function in ubiquitination and degradation of membrane-bound, but not cytosolic, beta-catenin, whose turnover may be required for alignment and growth of the sarcomere, the basic contractile unit of myofibers... - A Wnt-Wnt situationXi He
Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
Dev Cell 4:791-7. 2003.... - A component of the ARC/Mediator complex required for TGF beta/Nodal signallingYoichi Kato
Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 418:641-6. 2002..Thus ARC105 is a specific and key ARC/Mediator component linking TGF beta/Activin/Nodal/Smad2/3 signalling to transcriptional activation... - Antagonizing Wnt and FGF receptors: an enemy from within (the ER)Xi He
Division of Neuroscience, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
Cell 120:156-8. 2005..Shisa thus antagonizes Wnt and FGF signaling cell-autonomously, thereby promoting anterior patterning in Xenopus... - Threonine 41 in beta-catenin serves as a key phosphorylation relay residue in beta-catenin degradationGeng Wu
Division of Neuroscience, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
Biochemistry 45:5319-23. 2006..These results suggest that Thr41 functions to bridge sequential phosphorylation from Ser45 to Ser37 and provide further insights into the discrete steps and logic in beta-catenin phosphorylation-degradation... - SnapShot: Wnt/beta-catenin signalingBryan T MacDonald
The F.M. Kirb Neurobiology Center, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
Cell 131:1204. 2007 - Distinct strategies to make nucleosomal DNA accessibleHua-Ying Fan
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Mol Cell 11:1311-22. 2003..This specialized ability to make central sites accessible should allow SWI/SNF family complexes to facilitate binding of nuclear factors in chromatin environments where adjacent nucleosomes might otherwise constrain mobility... - Wnt/beta-catenin signaling: new (and old) players and new insightsHe Huang
The F M Kirby Neurobiology Center, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
Curr Opin Cell Biol 20:119-25. 2008..Here we review some recent discoveries in these two areas, and highlight some crucial questions that remain to be resolved... - Tuberous sclerosis complex proteins control axon formationYong Jin Choi
The F M Kirby Neurobiology Center, Department of Neurology, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
Genes Dev 22:2485-95. 2008.... - Bone mass is inversely proportional to Dkk1 levels in miceBryan T MacDonald
Division of Neuroscience, Department of Orthopedic Surgery, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
Bone 41:331-9. 2007..Thus DKK1 is a negative regulator of normal bone homeostasis in vivo. Our study suggests that manipulation of DKK1 function or expression may have therapeutic significance for the treatment of low bone mass disorders... - Lrp5 functions in bone to regulate bone massYajun Cui
Orthopedic Research Laboratories, Department of Orthopedic Surgery, Children s Hospital, Boston, Massachusetts, USA
Nat Med 17:684-91. 2011..These data indicate that Lrp5 signaling functions locally, and they suggest that increasing LRP5 signaling in mature bone cells may be a strategy for treating human disorders associated with low bone mass, such as osteoporosis... - A finger on the pulse of Wnt receptor signalingBryan T MacDonald
The F M Kirby Neurobiology Center, Boston Children s Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
Cell Res 22:1410-2. 2012..R-spondin binds to ZNRF3, in addition to transmembrane LGR4/5 receptors, to antagonize degradation of the Wnt receptors by ZNRF3, thereby resulting in increased Frizzled and LRP6 levels and a greater Wnt response... - Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesisKoichi Akashi
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Blood 101:383-9. 2003..These data support the hypothesis that stem cells possess a wide-open chromatin structure to maintain their multipotentiality, which is progressively quenched as they go down a particular pathway of differentiation... - Molecular cloning and developmental expression of Par-1/MARK homologues XPar-1A and XPar-1B from Xenopus laevisOlga Ossipova
Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Gene Expr Patterns 2:145-50. 2002.... - The DIX domain targets dishevelled to actin stress fibres and vesicular membranesDaniel G S Capelluto
Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262, USA
Nature 419:726-9. 2002..We propose that partitioning of Dvl into cytoskeletal and vesicular pools by the DIX domain represents a point of divergence in Wnt signalling... - Novel cross talk of Kruppel-like factor 4 and beta-catenin regulates normal intestinal homeostasis and tumor repressionWen Zhang
Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 1048, USA
Mol Cell Biol 26:2055-64. 2006..Our findings suggest that the cross talk of KLF4 and beta-catenin plays a critical role in homeostasis of the normal intestine as well as in tumorigenesis of colorectal cancers... - Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulationRaymond Habas
Laboratory of Molecular Genetics, National Institutes of Child Health and Human Development, Bethesda, Maryland 20892 2790, USA
Genes Dev 17:295-309. 2003..We propose that parallel activation of Rac and Rho pathways by Wnt/Fz signaling is required for cell polarity and movements during vertebrate gastrulation... - BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signalingXi C He
Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, Missouri 64110, USA
Nat Genet 36:1117-21. 2004..Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number... - Cell signaling: moving to a Wnt-RapRaymond Habas
Research Tower, Room 629, Department of Biochemistry, UMDNJ Robert Wood Johnson School of Medicine, 675 Hoes Lane, Piscataway, New Jersey 08854, USA
Curr Biol 17:R474-7. 2007..A recent study reveals that casein kinase Iepsilon mediates an additional novel non-canonical Wnt pathway via the activation of the Rap1 GTPase during vertebrate gastrulation... - LRP6 expression promotes cancer cell proliferation and tumorigenesis by altering beta-catenin subcellular distributionYonghe Li
Department of Pediatrics, St Louis Children s Hospital, Washington University School of Medicine, St Louis, MO 63110, USA
Oncogene 23:9129-35. 2004..Finally, we demonstrate that LRP6 expression promotes tumorigenesis in vivo. These results thus indicate that LRP6 may function as a potential oncogenic protein by modulating Wnt/beta-catenin signaling... - Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathwaysYi Zhang
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
J Biol Chem 277:17706-12. 2002..Furthermore, our data suggest that CKI may provide a possible switch mechanism for Axin function in the regulation of Wnt and JNK pathways... - Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1Zhen G Luo
Department of Neurobiology, Civitan International Research Center, University of Alabama at Birmingham, 1530 Third Avenue South, Birmingham, AL 35294, USA
Neuron 35:489-505. 2002..Inhibition of PAK1 activity attenuates AChR clustering. These results demonstrate important roles of Dvl and PAK in Agrin/MuSK-induced AChR clustering and reveal a novel function of Dvl in synapse development... - CD4-CD8 lineage commitment: an inside viewDietmar J Kappes
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
Nat Immunol 6:761-6. 2005..Finally, identification of the transcription factor Th-POK as a central component of the CD4 lineage-determining pathway has provided a new starting point from which to unravel this intriguing process 'from the inside out'... - The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitmentXiao He
Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111, USA
Nature 433:826-33. 2005.... - Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome C releaseTae-Hyoung Kim
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
Mol Biol Cell 15:3061-72. 2004..These findings thus suggest that interactions of Bid with mitochondrial cardiolipin at the contact site can contribute significantly to its functions... - Activation of Rho and Rac by Wnt/frizzled signalingRaymond Habas
Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Piscataway, USA
Methods Enzymol 406:500-11. 2006..In this chapter, we describe biochemical assays for the detection of Wnt/Fz activation of Rho and Rac in both mammalian cells and Xenopus embryo explants... - TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growthKen Inoki
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
Cell 126:955-68. 2006..Furthermore, the sequential phosphorylation of TSC2 by AMPK and GSK3 reveals a molecular mechanism of signal integration in cell growth regulation... - Modulation of LRP6-mediated Wnt signaling by molecular chaperone MesdYonghe Li
Department of Pediatrics, Washington University School of Medicine and St Louis Children s Hospital, MO 63110, USA
FEBS Lett 580:5423-8. 2006..Our results present novel mechanisms by which Mesd and LRP6 modulate Wnt signaling... - Adenomatous polyposis coli (APC) differentially regulates beta-catenin phosphorylation and ubiquitination in colon cancer cellsJun Yang
Sealy Center for Cancer Cell Biology and Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
J Biol Chem 281:17751-7. 2006..The APC domains required for beta-catenin ubiquitination were analyzed. Our results suggest that APC regulates beta-catenin phosphorylation and ubiquitination by distinct domains and by separate molecular mechanisms... - A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase IIHenri-Marc Bourbon
Mol Cell 14:553-7. 2004 - Identification of the haematopoietic stem cell niche and control of the niche sizeJiwang Zhang
Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
Nature 425:836-41. 2003..We conclude that SNO cells lining the bone surface function as a key component of the niche to support HSCs, and that BMP signalling through BMPRIA controls the number of HSCs by regulating niche size... - Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cellsHongyan Jian
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
Genes Dev 20:666-74. 2006.... - Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamicsXinjun Zhang
Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China
J Cell Sci 119:1053-62. 2006..These results suggest that Varp is a potential Rab21 guanine nucleotide exchange factor and might regulate endosome dynamics in vivo... - CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locusXi He
Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia, PA 19111, USA
Immunity 28:346-58. 2008..We propose a silencer-dependent model of lineage choice, whereby inactivation of the DRE silencer by a strong TCR signal leads to CD4 commitment, whereas continued silencer activity leads to CD8 commitment... - Identification and comparative expression analyses of Daam genes in mouse and XenopusMasa aki Nakaya
Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute Frederick, NIH, 1050 Boyles St, Bldg 539, Rm 218, Frederick, MD 21702, USA
Gene Expr Patterns 5:97-105. 2004..Our results demonstrate that Daams are expressed in tissues known to require Wnts and are consistent with Daams being effectors of Wnt signaling during vertebrate development...
Research Grants
- Studies of Wnt Receptor interaction with agonists and antagonistsXi He; Fiscal Year: 2010..This proposal aims to understand the molecular nature of the interaction between a key family of signaling molecules and their receptors that have been associated with many diseases. ..
- LRP6 phosphorylation in Wnt/beta-catenin signalingXi He; Fiscal Year: 2007..These experiments will significantly enhance the understanding of Wnt receptor activation and Wnt signal transduction in development and disease. ..
- Wnt-LRP interaction in Wnt signal transductionXi He; Fiscal Year: 2007..We believe that this comprehensive study will provide significant insights into Wnt-LRP interaction in development and diseases. ..
- WNT FRIZZLED INTERACTION IN WNT SIGNAL TRANSDUCTIONXi He; Fiscal Year: 2003....
- Wnt/beta-catenin signaling: phosphorylation regulation of Wnt receptor-Axin interXi He; Fiscal Year: 2010..Our study will provide better understanding of human embryonic development and pathogenesis of cancer. ..