Xi He, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2257
Fax: (617) 730-1953


xi.he@childrens.harvard.edu

Xi He, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Professor, Neurology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are interested in the mechanism of Wnt signal transduction and its roles in early vertebrate development, in brain development and in human tumorigenesis. We are also interested in the signaling and transcriptional regulatory mechanism during vertebrate neural induction. We perform our studies in both the Xenopus embryo system and the mammalian cell culture system.

Publications

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  • Zhang X, Cheong SM, Amado NG, Reis AH, MacDonald BT, Zebisch M, Jones EY, Abreu JG, He X. Notum Is Required for Neural and Head Induction via Wnt Deacylation, Oxidation, and Inactivation. Dev Cell 2015; 32:719-30. PubMed
  • Wang L, Shalek AK, Lawrence M, Ding R, Gaublomme JT, Pochet N, Stojanov P, Sougnez C, Shukla SA, Stevenson KE, Zhang W, Wong J, Sievers QL, MacDonald BT, Vartanov AR, Goldstein NR, Neuberg D, He X, Lander E, Hacohen N, Regev A, Getz G, Brown JR, Park H, Wu CJ. Somatic mutation as a mechanism of Wnt/硫-catenin pathway activation in CLL. Blood 2014. PubMed
  • MacDonald BT, Hien A, Zhang X, Iranloye O, Virshup DM, Waterman ML, He X. Disulfide Bond Requirements for Active Wnt Ligands. J Biol Chem 2014. PubMed
  • Zhang X, He X. PAF makes it EZ(H2) for 硫-catenin transactivation. Mol Cell 2013; 52:157-8. PubMed
  • Kim SE, Huang H, Zhao M, Zhang X, Zhang A, Semonov MV, MacDonald BT, Zhang X, Garcia Abreu J, Peng L, He X. Wnt stabilization of 硫-catenin reveals principles for morphogen receptor-scaffold assemblies. Science 2013; 340:867-70. PubMed
  • Xu Y, Xu C, Kato A, Tempel W, Abreu JG, Bian C, Hu Y, Hu D, Zhao B, Cerovina T, Diao J, Wu F, He HH, Cui Q, Clark E, Ma C, Barbara A, Veenstra GJ, Xu G, Kaiser UB, Liu XS, Sugrue SP, He X, Min J, Kato Y, Shi YG. Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development. Cell 2012; 151:1200-13. PubMed
  • MacDonald BT, He X. Frizzled and LRP5/6 receptors for Wnt/硫-catenin signaling. Cold Spring Harb Perspect Biol 2012. PubMed
  • Macaulay IC, Thon JN, Tijssen MR, Steele BM, Macdonald BT, Meade G, Burns P, Rendon A, Salunkhe V, Murphy RP, Bennett C, Watkins NA, He X, Fitzgerald DJ, Italiano JE, Maguire PB. Canonical Wnt signaling in megakaryocytes regulates proplatelet formation. Blood 2012. PubMed
  • Li Z, He X, Feng J. Dicer is essential for neuronal polarity. Int J Dev Neurosci 2012; 30:607-11. PubMed
  • Macdonald BT, He X. A finger on the pulse of Wnt receptor signaling. Cell Res 2012; 22:1410-2. PubMed
  • Bienz M, He X. Biochemistry. A lipid linchpin for Wnt-Fz docking. Science 2012; 337:44-5. PubMed
  • Zhang X, Abreu JG, Yokota C, MacDonald BT, Singh S, Coburn KL, Cheong SM, Zhang MM, Ye QZ, Hang HC, Steen H, He X. Tiki1 is required for head formation via Wnt cleavage-oxidation and inactivation. Cell 2012; 149:1565-77. PubMed
  • Peereboom DM, Supko JG, Carson KA, Batchelor T, Phuphanich S, Lesser G, Mikkelson T, Fisher J, Desideri S, He X, Grossman SA, . A phase I/II trial and pharmacokinetic study of ixabepilone in adult patients with recurrent high-grade gliomas. J. Neurooncol. 2010; 100:261-8. PubMed
  • Xu W, He X. DEEP Insights through the DEP Domain. Structure 2010; 18:1223-5. PubMed
  • Lee G, Goretsky T, Managlia E, Dirisina R, Singh AP, Brown JB, May R, Yang GY, Ragheb JW, Evers BM, Weber CR, Turner JR, He XC, Katzman RB, Li L, Barrett TA. Phosphoinositide 3-Kinase Signaling Mediates beta-Catenin Activation in Intestinal Epithelial Stem and Progenitor Cells in Colitis. Gastroenterology 2010; 139:869-81, 881.e1-9. PubMed
  • Bird GH, Madani N, Perry AF, Princiotto AM, Supko JG, He X, Gavathiotis E, Sodroski JG, Walensky LD. Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic. Proc Natl Acad Sci U S A 2010; 107:14093-8. PubMed
  • Park K, He X, Lee HO, Hua X, Li Y, Wiest D, Kappes DJ. TCR-mediated ThPOK induction promotes development of mature (CD24-) gammadelta thymocytes. EMBO J 2010; 29:2329-41. PubMed
  • Zhang B, Abreu JG, Zhou K, Chen Y, Hu Y, Zhou T, He X, Ma JX. Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family. Proc Natl Acad Sci U S A 2010; 107:6900-5. PubMed
  • Liu C, He X. Destruction of a Destructor: A New Avenue for Cancer Therapeutics Targeting the Wnt Pathway. 2010; 2:70-3. PubMed
  • Zhong H, Zou H, Semenov MV, Moshinsky D, He X, Huang H, Li S, Quan J, Yang Z, Lin S. Characterization and development of novel small-molecules inhibiting GSK3 and activating Wnt signaling. Mol Biosyst 2009; 5:1356-60. PubMed
  • MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 2009; 17:9-26. PubMed
  • Wu G,Huang H,Garcia Abreu J,He X. Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS ONE 2009; 4:e4926. PubMed
  • Blakeley JO,Olson J,Grossman SA,He X,Weingart J,Supko JG. Effect of blood brain barrier permeability in recurrent high grade gliomas on the intratumoral pharmacokinetics of methotrexate: a microdialysis study. J Neurooncol 2008; 91:51-8. PubMed
  • Zhu AX,Ready N,Clark JW,Safran H,Amato A,Salem N,Pace S,He X,Zvereva N,Lynch TJ,Ryan DP,Supko JG. Phase I and pharmacokinetic study of gimatecan given orally once a week for 3 of 4 weeks in patients with advanced solid tumors. Clin Cancer Res 2009; 15:374-81. PubMed
  • Miech C,Pauer HU,He X,Schwarz TL. Presynaptic local signaling by a canonical wingless pathway regulates development of the Drosophila neuromuscular junction. J Neurosci 2008; 28:10875-84. PubMed
  • Choi YJ,Di Nardo A,Kramvis I,Meikle L,Kwiatkowski DJ,Sahin M,He X. Tuberous sclerosis complex proteins control axon formation. Genes Dev 2008; 22:2485-95. PubMed
  • Semenov MV,Zhang X,He X. DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation. J Biol Chem 2008; 283:21427-32. PubMed
  • He X,Fan HY,Garlick JD,Kingston RE. Diverse regulation of SNF2h chromatin remodeling by noncatalytic subunits. Biochemistry 2008; 47:7025-33. PubMed
  • Macdonald BT, Yokota C, Tamai K, Zeng X, He X. Wnt signal amplification: activity, cooperativity and regulation of multiple intracellular PPPSP motifs in the Wnt coreceptor LRP6. J Biol Chem 2008; 283:16115-23. PubMed
  • Miao XS,Song P,Savage RE,Zhong C,Yang RY,Kizer D,Wu H,Volckova E,Ashwell MA,Supko JG,He X,Chan TC. Identification of the in vitro metabolites of 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (ARQ 501; beta-lapachone) in whole blood. Drug Metab Dispos 2008; 36:641-8. PubMed
  • Huang H, He X. Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol 2008; 20:119-25. PubMed
  • He X, Park K, Wang H, He X, Zhang Y, Hua X, Li Y, Kappes DJ. CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus. Immunity 2008; 28:346-58. PubMed
  • Zeng X, Huang H, Tamai K, Zhang X, Harada Y, Yokota C, Almeida K, Wang J, Doble B, Woodgett J, Wynshaw-Boris A, Hsieh JC, He X. Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions. Development 2007; 135:367-75. PubMed
  • He X. Cilia put a brake on Wnt signalling. Nat Cell Biol 2008; 10:11-3. PubMed
  • Semenov MV, Habas R, Macdonald BT, He X. SnapShot: Noncanonical Wnt Signaling Pathways. Cell 2007; 131:1378. PubMed
  • Macdonald BT, Semenov MV, He X. SnapShot: Wnt/beta-catenin signaling. Cell 2007; 131:1204. PubMed
  • Akingbemi BT,Braden TD,Kemppainen BW,Hancock KD,Sherrill JD,Cook SJ,He X,Supko JG. Exposure to phytoestrogens in the perinatal period affects androgen secretion by testicular Leydig cells in the adult rat. Endocrinology 2007; 148:4475-88. PubMed
  • Harada Y, Yokota C, Habas R, Slusarski DC, He X. Retinoic acid-inducible G protein-coupled receptors bind to frizzled receptors and may activate non-canonical Wnt signaling. Biochem Biophys Res Commun 2007; 358:968-75. PubMed
  • Habas R, He X. Cell signaling: moving to a Wnt-Rap. Curr Biol 2007; 17:R474-7. PubMed
  • Donne AJ, Hampson L, He XT, Rothera MP, Homer JJ, Hampson IN. The effect of cidofovir on cellular HPV E6 level, a possible early therapeutic indicator for respiratory papillomatosis therapies. Clin Otolaryngol 2007; 32:230. PubMed
  • Wei Q, Yokota C, Semenov MV, Doble B, Woodgett J, He X. R-spondin1 Is a High Affinity Ligand for LRP6 and Induces LRP6 Phosphorylation and beta-Catenin Signaling. J Biol Chem 2007; 282:15903-11. PubMed
  • Yu A, Rual JF, Tamai K, Harada Y, Vidal M, He X, Kirchhausen T. Association of Dishevelled with the clathrin AP-2 adaptor is required for Frizzled endocytosis and planar cell polarity signaling. Dev Cell 2007; 12:129-41. PubMed
  • Semenov MV, He X. LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST. J Biol Chem 2006; 281:38276-84. PubMed
  • He X. Unwinding a path to nuclear beta-catenin. Cell 2006; 127:40-2. PubMed
  • Li Y, Lu W, He X, Bu G. Modulation of LRP6-mediated Wnt signaling by molecular chaperone Mesd. FEBS Lett 2006; 580:5423-8. PubMed
  • Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, He X, MacDougald OA, You M, Williams BO, Guan KL. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 2006; 126:955-68. PubMed
  • He X, Chen MG, Lin GX, Ma Q. Arsenic induces NAD(P)H:quinone oxidoreductase I by disrupting the NRF2/KEAP1/CUL3 complex and recruiting NRF2/MAF to are enhancer. J Biol Chem 2006; 281:23620-31. PubMed
  • He X, Axelrod JD. A WNTer wonderland in Snowbird. Development 2006; 133:2597-603. PubMed
  • Eder JP, Ryan DP, Appleman L, Zhu AX, Puchalski T, He X, Sonnichsen DS, Cooper M, Wright J, Clark JW, Supko JG. Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 administered as a weekly 24 h continuous intravenous infusion in patients with advanced solid tumors. Cancer Chemother Pharmacol 2005; 58:107-116. PubMed
  • Yang J, Zhang W, Evans PM, Chen X, He X, Liu C. Adenomatous polyposis coli (APC) differentially regulates beta-catenin phosphorylation and ubiquitination in colon cancer cells. J Biol Chem 2006; 281:17751-7. PubMed
  • Wu G, He X. Threonine 41 in beta-catenin serves as a key phosphorylation relay residue in beta-catenin degradation. Biochemistry 2006; 45:5319-23. PubMed
  • Zhang W, Chen X, Kato Y, Evans PM, Yuan S, Yang J, Rychahou PG, Yang VW, He X, Evers BM, Liu C. Novel cross talk of Kruppel-like factor 4 and beta-catenin regulates normal intestinal homeostasis and tumor repression. Mol Cell Biol 2006; 26:2055-64. PubMed
  • Klein A, He X, Roche M, Mallett A, Duska L, Supko JG, Seiden MV. Prolonged stabilization of platinum-resistant ovarian cancer in a single patient consuming a fermented soy therapy. Gynecol Oncol 2005; 100:205-9. PubMed
  • Habas R, He X. Activation of Rho and Rac by Wnt/frizzled signaling. Methods Enzymol 2006; 406:500-11. PubMed
  • Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J, He X. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 2005; 438:873-7. PubMed
  • Merchan JR, Jayaram DR, Supko JG, He X, Bubley GJ, Sukhatme VP. Increased endothelial uptake of paclitaxel as a potential mechanism for its antiangiogenic effects: potentiation by Cox-2 inhibition. Int J Cancer 2004; 113:490-8. PubMed
  • Kato Y, Shi Y, He X. Neuralization of the Xenopus embryo by inhibition of p300/ CREB-binding protein function. J Neurosci 1999; 19:9364-73. PubMed
  • Liu C, Kato Y, Zhang Z, Do VM, Yankner BA, He X. beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation. Proc Natl Acad Sci U S A 1999; 96:6273-8. PubMed
  • He X, Saint-Jeannet JP, Wang Y, Nathans J, Dawid I, Varmus H. A member of the Frizzled protein family mediating axis induction by Wnt-5A. Science 1997; 275:1652-4. PubMed
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