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Wade Harper, PH.D.

TitleBert and Natalie Vallee Professor of Molecular Pathology
InstitutionHarvard Medical School
DepartmentCell Biology
AddressHarvard Medical School
Pathology - Harper Lab, NRB 940e
77 Avenue Louis Pasteur
Boston MA 02115
Phone617/432-6590
Fax617/432-6591

 Mentoring 
 current student opportunities
Available: 11/26/12, Expires: 11/28/14

Tumor suppressors can function to maintain cell proliferation control pathways in an inactive state by suppressing positively acting growth regulators. Such growth control pathways can be viewed as constellations of protein complexes that assemble into a series of inter-connected sub-networks. The Hippo pathway is a protein kinase driven phosphorylation cascade containing multiple tumor suppressors that negatively control cell growth and is deactivated in many cancer types, such as breast, kidney, and liver cancers. The project will utilize emerging quantitative proteomic methods to define a comprehensive network map of Hippo pathway organization and dynamics in normal cells and in cells lacking critical upstream tumor suppressors. These studies aim to uncover crucial architectural elements in the Hippo pathway that promote tumorigenesis.


 Research 
 research resources
This researcher has shared information about their research resources
in the eagle-i Network. To update or add resource records, contact
eagle-i@hms.harvard.edu.
DNA Resource Core (DF/HCC) - Core services (7), Gene knockdown screening libraries (1), Instruments (6), Plasmids (2) and cDNA libraries (2)

 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Harper JW, King RW. Stuck in the middle: drugging the ubiquitin system at the e2 step. Cell. 2011 Jun 24; 145(7):1007-9.
    View in: PubMed
  2. Harper JW, Elledge SJ. The DNA damage response: ten years after. Mol Cell. 2007 Dec 14; 28(5):739-45.
    View in: PubMed
  3. Harper JW, Schulman BA. Structural complexity in ubiquitin recognition. Cell. 2006 Mar 24; 124(6):1133-6.
    View in: PubMed
  4. Ayala G, Thompson T, Yang G, Frolov A, Li R, Scardino P, Ohori M, Wheeler T, Harper W. High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence. Clin Cancer Res. 2004 Oct 1; 10(19):6572-8.
    View in: PubMed
  5. Baumgartner B, Harper JW. Deafening cycle. Nat Cell Biol. 2003 May; 5(5):385-7.
    View in: PubMed
  6. Wei Y, Jin J, Harper JW. The cyclin E/Cdk2 substrate and Cajal body component p220(NPAT) activates histone transcription through a novel LisH-like domain. Mol Cell Biol. 2003 May; 23(10):3669-80.
    View in: PubMed
  7. Wang Y, Shirogane T, Liu D, Harper JW, Elledge SJ. Exit from exit: resetting the cell cycle through Amn1 inhibition of G protein signaling. Cell. 2003 Mar 7; 112(5):697-709.
    View in: PubMed
  8. Passmore LA, McCormack EA, Au SW, Paul A, Willison KR, Harper JW, Barford D. Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. EMBO J. 2003 Feb 17; 22(4):786-96.
    View in: PubMed
  9. Harper JW, Burton JL, Solomon MJ. The anaphase-promoting complex: it's not just for mitosis any more. Genes Dev. 2002 Sep 1; 16(17):2179-206.
    View in: PubMed
  10. Nalepa G, Harper JW. Efp: a ring of independence? Nat Med. 2002 Jul; 8(7):661-2.
    View in: PubMed
  11. Jin J, Harper JW. RING finger specificity in SCF-driven protein destruction. Dev Cell. 2002 Jun; 2(6):685-7.
    View in: PubMed
  12. Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature. 2002 Apr 18; 416(6882):703-9.
    View in: PubMed
  13. Leng X, Noble M, Adams PD, Qin J, Harper JW. Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4. Mol Cell Biol. 2002 Apr; 22(7):2242-54.
    View in: PubMed
  14. Harper JW. A phosphorylation-driven ubiquitination switch for cell-cycle control. Trends Cell Biol. 2002 Mar; 12(3):104-7.
    View in: PubMed
  15. Au SW, Leng X, Harper JW, Barford D. Implications for the ubiquitination reaction of the anaphase-promoting complex from the crystal structure of the Doc1/Apc10 subunit. J Mol Biol. 2002 Mar 1; 316(4):955-68.
    View in: PubMed
  16. Pogue BW, Kaufman HB, Zelenchuk A, Harper W, Burke GC, Burke EE, Harper DM. Analysis of acetic acid-induced whitening of high-grade squamous intraepithelial lesions. J Biomed Opt. 2001 Oct; 6(4):397-403.
    View in: PubMed
  17. Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW, Elledge SJ. Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science. 2001 Oct 5; 294(5540):173-7.
    View in: PubMed
  18. Harper JW. Protein destruction: adapting roles for Cks proteins. Curr Biol. 2001 Jun 5; 11(11):R431-5.
    View in: PubMed
  19. Schulman BA, Carrano AC, Jeffrey PD, Bowen Z, Kinnucan ER, Finnin MS, Elledge SJ, Harper JW, Pagano M, Pavletich NP. Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex. Nature. 2000 Nov 16; 408(6810):381-6.
    View in: PubMed
  20. Ma T, Van Tine BA, Wei Y, Garrett MD, Nelson D, Adams PD, Wang J, Qin J, Chow LT, Harper JW. Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription. Genes Dev. 2000 Sep 15; 14(18):2298-313.
    View in: PubMed
  21. Stepanova L, Finegold M, DeMayo F, Schmidt EV, Harper JW. The oncoprotein kinase chaperone CDC37 functions as an oncogene in mice and collaborates with both c-myc and cyclin D1 in transformation of multiple tissues. Mol Cell Biol. 2000 Jun; 20(12):4462-73.
    View in: PubMed
  22. Winston JT, Chu C, Harper JW. Culprits in the degradation of cyclin E apprehended. Genes Dev. 1999 Nov 1; 13(21):2751-7.
    View in: PubMed
  23. Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW. A family of mammalian F-box proteins. Curr Biol. 1999 Oct 21; 9(20):1180-2.
    View in: PubMed
  24. Wang Y, Penfold S, Tang X, Hattori N, Riley P, Harper JW, Cross JC, Tyers M. Deletion of the Cul1 gene in mice causes arrest in early embryogenesis and accumulation of cyclin E. Curr Biol. 1999 Oct 21; 9(20):1191-4.
    View in: PubMed
  25. Kitagawa K, Skowyra D, Elledge SJ, Harper JW, Hieter P. SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex. Mol Cell. 1999 Jul; 4(1):21-33.
    View in: PubMed
  26. Koepp DM, Harper JW, Elledge SJ. How the cyclin became a cyclin: regulated proteolysis in the cell cycle. Cell. 1999 May 14; 97(4):431-4.
    View in: PubMed
  27. Harper JW, Elledge SJ. Skipping into the E2F1-destruction pathway. Nat Cell Biol. 1999 May; 1(1):E5-7.
    View in: PubMed
  28. Skowyra D, Koepp DM, Kamura T, Conrad MN, Conaway RC, Conaway JW, Elledge SJ, Harper JW. Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. Science. 1999 Apr 23; 284(5414):662-5.
    View in: PubMed
  29. Kamura T, Koepp DM, Conrad MN, Skowyra D, Moreland RJ, Iliopoulos O, Lane WS, Kaelin WG, Elledge SJ, Conaway RC, Harper JW, Conaway JW. Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science. 1999 Apr 23; 284(5414):657-61.
    View in: PubMed
  30. Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW. The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. Genes Dev. 1999 Feb 1; 13(3):270-83.
    View in: PubMed
  31. Ma T, Zou N, Lin BY, Chow LT, Harper JW. Interaction between cyclin-dependent kinases and human papillomavirus replication-initiation protein E1 is required for efficient viral replication. Proc Natl Acad Sci U S A. 1999 Jan 19; 96(2):382-7.
    View in: PubMed
  32. Zhang P, Wong C, Liu D, Finegold M, Harper JW, Elledge SJ. p21(CIP1) and p57(KIP2) control muscle differentiation at the myogenin step. Genes Dev. 1999 Jan 15; 13(2):213-24.
    View in: PubMed
  33. Zhang P, Wong C, DePinho RA, Harper JW, Elledge SJ. Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of tissue growth and development. Genes Dev. 1998 Oct 15; 12(20):3162-7.
    View in: PubMed
  34. Connell-Crowley L, Elledge SJ, Harper JW. G1 cyclin-dependent kinases are sufficient to initiate DNA synthesis in quiescent human fibroblasts. Curr Biol. 1998 Jan 1; 8(1):65-8.
    View in: PubMed
  35. Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell. 1997 Oct 17; 91(2):209-19.
    View in: PubMed
  36. Leng X, Connell-Crowley L, Goodrich D, Harper JW. S-Phase entry upon ectopic expression of G1 cyclin-dependent kinases in the absence of retinoblastoma protein phosphorylation. Curr Biol. 1997 Sep 1; 7(9):709-12.
    View in: PubMed
  37. Zhang P, LiƩgeois NJ, Wong C, Finegold M, Hou H, Thompson JC, Silverman A, Harper JW, DePinho RA, Elledge SJ. Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome. Nature. 1997 May 8; 387(6629):151-8.
    View in: PubMed
  38. Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996 Jul 26; 86(2):263-74.
    View in: PubMed
  39. Stepanova L, Leng X, Parker SB, Harper JW. Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev. 1996 Jun 15; 10(12):1491-502.
    View in: PubMed
  40. Deng C, Zhang P, Harper JW, Elledge SJ, Leder P. Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell. 1995 Aug 25; 82(4):675-84.
    View in: PubMed
  41. Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ. p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev. 1995 Mar 15; 9(6):650-62.
    View in: PubMed
  42. Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A, Olson EN, Harper JW, Elledge SJ. p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. Science. 1995 Feb 17; 267(5200):1024-7.
    View in: PubMed
  43. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993 Nov 19; 75(4):805-16.
    View in: PubMed
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