Wade Harper, Ph.D.

Wade Harper, Ph.D.

Bert and Natalie Vallee Professor of Molecular Pathology (HMS)
Professor of Cell Biology (HMS)
Chair of the Department of Cell Biology (HMS)

Wade Harper, Ph.D., is the B and N Vallee Professor of Molecular Pathology, a Professor of Cell Biology, and the Chair of Cell Biology in the Blavatnik Institute at Harvard Medical School. He received his Ph.D. in Chemistry from Georgia Institute of Technology, prior to performing post-doctoral work in protein biochemistry of growth factors at Harvard Medical School. He joined the faculty in the Department of Biochemistry and Molecular Biology at Baylor College of Medicine in 1988 and subsequently moved to the Department of Pathology at Harvard Medical School (in 2003) and to the Department of Cell Biology in 2011.

The Harper Lab studies mechanisms underlying cellular homeostasis and signaling, with a focus on the ubiquitin system and the autophagy-lysosome system. The interest in the ubiquitin-proteasome system in the Harper Lab initially emerged through studies to understand how cell cycle regulators (cyclins and CDK inhibitors) are degraded to control cell cycle transitions, resulting in the discovery of cullin-RING ubiquitin ligases, and their roles in phosphorylation-dependent protein degradation. The Harper Lab currently uses quantitative proteomics, imaging, and biochemical approaches to elucidate underlying biochemical mechanisms controlling protein turnover, and applies these approaches to examine regulatory pathways relevant to various neurodegenerative disease, including Parkinson’s and Alzheimer’s diseases. A major focus currently is the PARKIN ubiquitin ligase, which controls turnover of damaged mitochondria via the autophagy pathway and is mutated in Parkinson’s Disease. The Harper Lab, together with the Gygi Lab at HMS, is also using proteomics to develop a large-scale human protein interaction network including the majority of proteins encoded by the human genome.

Harvard Medical School

Dept. of Cell Biology, C-462A

240 Longwood Avenue

Boston, MA 02115

Lab telephone: 617-432-6590

QIL1 is a novel mitochondrial protein required for MICOS complex stability and cristae morphology.
Authors: Authors: Guarani V, McNeill EM, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1231877">Paulo JA</a>, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1243594">Huttlin EL</a>, Fröhlich F, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1242109">Gygi SP</a>, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1246378">Van Vactor D</a>, Harper JW.
Elife
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Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.
Authors: Authors: Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, Dion PA, Leblond CS, Couthouis J, Lu YF, Wang Q, Krueger BJ, Ren Z, Keebler J, Han Y, Levy SE, Boone BE, Wimbish JR, Waite LL, Jones AL, Carulli JP, Day-Williams AG, Staropoli JF, Xin WW, Chesi A, Raphael AR, McKenna-Yasek D, Cady J, Vianney de Jong JM, Kenna KP, Smith BN, Topp S, Miller J, Gkazi A, Al-Chalabi A, van den Berg LH, Veldink J, Silani V, Ticozzi N, Shaw CE, Baloh RH, Appel S, Simpson E, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/62783836">Lagier-Tourenne C</a>, Pulst SM, Gibson S, Trojanowski JQ, Elman L, McCluskey L, Grossman M, Shneider NA, Chung WK, Ravits JM, Glass JD, Sims KB, Van Deerlin VM, Maniatis T, Hayes SD, Ordureau A, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/32571414">Swarup S</a>, Landers J, Baas F, Allen AS, Bedlack RS, Harper JW, Gitler AD, Rouleau GA, Brown R, Harms MB, Cooper GM, Harris T, Myers RM, Goldstein DB.
Science
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Proteomic analysis and identification of cellular interactors of the giant ubiquitin ligase HERC2.
Authors: Authors: Galligan JT, Martinez-Noël G, Arndt V, Hayes S, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/61342058">Chittenden TW</a>, Harper JW, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1237682">Howley PM</a>.
J Proteome Res
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Identification of TRIM27 as a novel degradation target of herpes simplex virus 1 ICP0.
Authors: Authors: Conwell SE, White AE, Harper JW, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1230084">Knipe DM</a>.
J Virol
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Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response.
Authors: Authors: Ciccia A, Huang JW, Izhar L, Sowa ME, Harper JW, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1240445">Elledge SJ</a>.
Proc Natl Acad Sci U S A
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Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis.
Authors: Authors: Ordureau A, Sarraf SA, Duda DM, Heo JM, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1250277">Jedrychowski MP</a>, Sviderskiy VO, Olszewski JL, Koerber JT, Xie T, Beausoleil SA, Wells JA, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1242109">Gygi SP</a>, Schulman BA, Harper JW.
Mol Cell
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Cyclin C is a haploinsufficient tumour suppressor.
Authors: Authors: Li N, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/26477489">Fassl A</a>, Chick J, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1257378">Inuzuka H</a>, Li X, Mansour MR, Liu L, Wang H, King B, Shaik S, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1242559">Gutierrez A</a>, Ordureau A, Otto T, Kreslavsky T, Baitsch L, Bury L, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1251759">Meyer CA</a>, Ke N, Mulry KA, Kluk MJ, Roy M, Kim S, Zhang X, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1230071">Geng Y</a>, Zagozdzon A, Jenkinson S, Gale RE, Linch DC, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1258961">Zhao JJ</a>, Mullighan CG, Harper JW, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1256535">Aster JC</a>, Aifantis I, von Boehmer H, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1242109">Gygi SP</a>, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1232367">Wei W</a>, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1236031">Look AT</a>, Sicinski P.
Nat Cell Biol
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TIF1? protein regulates epithelial-mesenchymal transition by operating as a small ubiquitin-like modifier (SUMO) E3 ligase for the transcriptional regulator SnoN1.
Authors: Authors: Ikeuchi Y, Dadakhujaev S, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/79985970">Chandhoke AS</a>, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1240847">Huynh MA</a>, Oldenborg A, Ikeuchi M, Deng L, Bennett EJ, Harper JW, Bonni A, Bonni S.
J Biol Chem
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Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide.
Authors: Authors: <a href="https://connects.catalyst.harvard.edu/Profiles/profile/61687296">Fischer ES</a>, Böhm K, Lydeard JR, Yang H, Stadler MB, Cavadini S, Nagel J, Serluca F, Acker V, Lingaraju GM, Tichkule RB, Schebesta M, Forrester WC, Schirle M, Hassiepen U, Ottl J, Hild M, Beckwith RE, Harper JW, Jenkins JL, Thomä NH.
Nature
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Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8.
Authors: Authors: Scott DC, Sviderskiy VO, Monda JK, Lydeard JR, Cho SE, Harper JW, Schulman BA.
Cell
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