Photo of Xu Wu, PhD

Xu Wu, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-4438
Fax: (617) 726-4453


xwu@cbrc2.mgh.harvard.edu

Photo of Xu Wu, PhD

Massachusetts General Hospital
Phone: (617) 726-4438
Fax: (617) 726-4453


xwu@cbrc2.mgh.harvard.edu

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Xu Wu, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Dermatology, Harvard Medical School
  • Principal Investigator, Cutaneous Biology Research Center, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

My research lies at the interface of chemistry and biology. We are using synthetic and medicinal chemistry methods to develop novel small molecule modulators of biological functions, aiming to 1).discover novel tools for stem cell and cancer biology; 2). pharmacologically identify and validate novel therapeutic targets; 3). discover novel signaling nodes, cross-talking and their physiological and pathological relevances. We use the combination of high throughput chemical screen, functional genomics and medicinal chemistry to discover new cancer targets and pharmacologically validate the new target. Specifically, we are developing small molecule modulators of Hedgehog, Wnt, and Hippo signaling, and study the differentiation and cellular senescence of various cancer cells.

Publications from Harvard Catalyst Profiles

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  • He L, Jhong JH, Chen Q, Huang KY, Strittmatter K, Kreuzer J, DeRan M, Wu X, Lee TY, Slavov N, Haas W, Marneros AG. Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors. Cell Rep 2021; 37:109955. PubMed
  • Shalhout SZ, Yang PY, Grzelak EM, Nutsch K, Shao S, Zambaldo C, Iaconelli J, Ibrahim L, Stanton C, Chadwick SR, Chen E, DeRan M, Li S, Hull M, Wu X, Chatterjee AK, Shen W, Camargo FD, Schultz PG, Bollong MJ. YAP-dependent proliferation by a small molecule targeting annexin A2. Nat Chem Biol 2021. PubMed
  • Li Q, Sun Y, Jarugumilli GK, Liu S, Dang K, Cotton JL, Xiol J, Chan PY, DeRan M, Ma L, Li R, Zhu LJ, Li JH, Leiter AB, Ip YT, Camargo FD, Luo X, Johnson RL, Wu X, Mao J. Lats1/2 Sustain Intestinal Stem Cells and Wnt Activation through TEAD-Dependent and Independent Transcription. Cell Stem Cell 2020; 26:675-692.e8. PubMed
  • Li H, Li Q, Dang K, Ma S, Cotton JL, Yang S, Zhu LJ, Deng AC, Ip YT, Johnson RL, Wu X, Punzo C, Mao J. YAP/TAZ Activation Drives Uveal Melanoma Initiation and Progression. Cell Rep 2019; 29:3200-3211.e4. PubMed
  • Niu J, Sun Y, Chen B, Zheng B, Jarugumilli GK, Walker SR, Hata AN, Mino-Kenudson M, Frank DA, Wu X. Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation. Nature 2019; 573:139-143. PubMed
  • Eelen G, Dubois C, Cantelmo AR, Goveia J, Brüning U, DeRan M, Jarugumilli G, van Rijssel J, Saladino G, Comitani F, Zecchin A, Rocha S, Chen R, Huang H, Vandekeere S, Kalucka J, Lange C, Morales-Rodriguez F, Cruys B, Treps L, Ramer L, Vinckier S, Brepoels K, Wyns S, Souffreau J, Schoonjans L, Lamers WH, Wu Y, Haustraete J, Hofkens J, Liekens S, Cubbon R, Ghesquière B, Dewerchin M, Gervasio FL, Li X, van Buul JD, Wu X, Carmeliet P. Role of glutamine synthetase in angiogenesis beyond glutamine synthesis. Nature 2018; 561:63-69. PubMed
  • Chen S, Zhu B, Yin C, Liu W, Han C, Chen B, Liu T, Li X, Chen X, Li C, Hu L, Zhou J, Xu ZX, Gao X, Wu X, Goding CR, Cui R. Palmitoylation-dependent activation of MC1R prevents melanomagenesis. Nature 2017; 549:399-403. PubMed
  • Chen B, Zheng B, DeRan M, Jarugumilli GK, Fu J, Brooks YS, Wu X. ZDHHC7-mediated S-palmitoylation of Scribble regulates cell polarity. Nat Chem Biol 2016. PubMed
  • Zheng B, Jarugumilli GK, Chen B, Wu X. Chemical Probes to Directly Profile Palmitoleoylation of Proteins. Chembiochem 2016. PubMed
  • Chan P, Han X, Zheng B, DeRan M, Yu J, Jarugumilli GK, Deng H, Pan D, Luo X, Wu X. Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway. Nat Chem Biol 2016; 12:282-9. PubMed
  • Bollu LR, Katreddy RR, Blessing AM, Pham N, Zheng B, Wu X, Weihua Z. Intracellular activation of EGFR by fatty acid synthase dependent palmitoylation. 2015. PubMed
  • Zheng B, Zhu S, Wu X. Clickable Analogue of Cerulenin as Chemical Probe to Explore Protein Palmitoylation. ACS Chem Biol 2014. PubMed
  • DeRan M, Yang J, Shen CH, Peters EC, Fitamant J, Chan P, Hsieh M, Zhu S, Asara JM, Zheng B, Bardeesy N, Liu J, Wu X. Energy stress regulates hippo-YAP signaling involving AMPK-mediated regulation of angiomotin-like 1 protein. Cell Rep 2014; 9:495-503. PubMed
  • Bassilana F, Carlson A, DaSilva JA, Grosshans B, Vidal S, Beck V, Wilmeringwetter B, Llamas LA, Showalter TB, Rigollier P, Bourret A, Ramamurthy A, Wu X, Harbinski F, Plonsky S, Lee L, Ruffner H, Grandi P, Schirle M, Jenkins J, Sailer AW, Bouwmeester T, Porter JA, Myer V, Finan PM, Tallarico JA, Kelleher JF, Seuwen K, Jain RK, Luchansky SJ. Target identification for a Hedgehog pathway inhibitor reveals the receptor GPR39. Nat Chem Biol 2014; 10:343-9. PubMed
  • Chen EY, DeRan MT, Ignatius MS, Grandinetti KB, Clagg R, McCarthy KM, Lobbardi RM, Brockmann J, Keller C, Wu X, Langenau DM. Glycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma. Proc Natl Acad Sci U S A 2014; 111:5349-54. PubMed
  • Liu J, Pan S, Hsieh MH, Ng N, Sun F, Wang T, Kasibhatla S, Schuller AG, Li AG, Cheng D, Li J, Tompkins C, Pferdekamper A, Steffy A, Cheng J, Kowal C, Phung V, Guo G, Wang Y, Graham MP, Flynn S, Brenner JC, Li C, Villarroel MC, Schultz PG, Wu X, McNamara P, Sellers WR, Petruzzelli L, Boral AL, Seidel HM, McLaughlin ME, Che J, Carey TE, Vanasse G, Harris JL. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A 2013; 110:20224-9. PubMed
  • Huang Z, Wu H, Chuai S, Xu F, Yan F, Englund N, Wang Z, Zhang H, Fang M, Wang Y, Gu J, Zhang M, Yang T, Zhao K, Yu Y, Dai J, Yi W, Zhou S, Li Q, Wu J, Liu J, Wu X, Chan H, Lu C, Atadja P, Li E, Wang Y, Hu M. NSD2 is recruited through its PHD domain to oncogenic gene loci to drive multiple myeloma. Cancer Res 2013; 73:6277-88. PubMed
  • Zheng B, DeRan M, Li X, Liao X, Fukata M, Wu X. 2-Bromopalmitate analogues as activity-based probes to explore palmitoyl acyltransferases. J Am Chem Soc 2013. PubMed
  • Cheng D, Han D, Gao W, Jing Q, Jiang J, Wan Y, Englund NP, Tuntland T, Wu X, Pan S. Design, synthesis, and structure-activity-relationship of phenyl imidazoles as potent Smoothened antagonists. Bioorg Med Chem Lett 2012; 22:6573-6. PubMed
  • Miller E, Yang J, DeRan M, Wu C, Su AI, Bonamy GM, Liu J, Peters EC, Wu X. Identification of serum-derived sphingosine-1-phosphate as a small molecule regulator of YAP. Chem Biol 2012; 19:955-62. PubMed
  • Johnson K, Zhu S, Tremblay MS, Payette JN, Wang J, Bouchez LC, Meeusen S, Althage A, Cho CY, Wu X, Schultz PG. A stem cell-based approach to cartilage repair. Science 2012; 336:717-21. PubMed
  • Skvara H, Kalthoff F, Meingassner JG, Wolff-Winiski B, Aschauer H, Kelleher JF, Wu X, Pan S, Mickel L, Schuster C, Stary G, Jalili A, David OJ, Emotte C, Antunes AM, Rose K, Decker J, Carlson I, Gardner H, Stuetz A, Bertolino AP, Stingl G, De Rie MA. Topical treatment of Basal cell carcinomas in nevoid Basal cell carcinoma syndrome with a smoothened inhibitor. J Invest Dermatol 2011. PubMed
  • Buonamici S, Williams J, Morrissey M, Wang A, Guo R, Vattay A, Hsiao K, Yuan J, Green J, Ospina B, Yu Q, Ostrom L, Fordjour P, Anderson DL, Monahan JE, Kelleher JF, Peukert S, Pan S, Wu X, Maira SM, García-Echeverría C, Briggs KJ, Watkins DN, Yao YM, Lengauer C, Warmuth M, Sellers WR, Dorsch M. Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci Transl Med 2010; 2:51ra70. PubMed
  • Hu XV, Rodrigues TM, Tao H, Baker RK, Miraglia L, Orth AP, Lyons GE, Schultz PG, Wu X. Identification of RING finger protein 4 (RNF4) as a modulator of DNA demethylation through a functional genomics screen. Proc Natl Acad Sci U S A 2010; 107:15087-92. PubMed
  • Zhu S, Wurdak H, Wang Y, Galkin A, Tao H, Li J, Lyssiotis CA, Yan F, Tu BP, Miraglia L, Walker J, Sun F, Orth A, Schultz PG, Wu X. A genomic screen identifies TYRO3 as a MITF regulator in melanoma. Proc Natl Acad Sci U S A 2009; 106:17025-30. PubMed
  • Wu X, Schultz PG. Synthesis at the interface of chemistry and biology. J Am Chem Soc 2009; 131:12497-515. PubMed
  • Zhu S, Wurdak H, Wang J, Lyssiotis CA, Peters EC, Cho CY, Wu X, Schultz PG. A small molecule primes embryonic stem cells for differentiation. Cell Stem Cell 2009; 4:416-26. PubMed
  • Wang W, Walker JR, Wang X, Tremblay MS, Lee JW, Wu X, Schultz PG. Identification of small-molecule inducers of pancreatic beta-cell expansion. Proc Natl Acad Sci U S A 2009; 106:1427-32. PubMed
  • Lyssiotis CA, Walker J, Wu C, Kondo T, Schultz PG, Wu X. Inhibition of histone deacetylase activity induces developmental plasticity in oligodendrocyte precursor cells. Proc Natl Acad Sci U S A 2007; 104:14982-7. PubMed
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DF/HCC members that share similar concepts* with Xu Wu, PhD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

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