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

Lab fax: 617-432-6591

The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia.
Authors: Authors: Nehme R, Pietiläinen O, Artomov M, Tegtmeyer M, Valakh V, Lehtonen L, Bell C, Singh T, Trehan A, Sherwood J, Manning D, Peirent E, Malik R, Guss EJ, Hawes D, Beccard A, Bara AM, Hazelbaker DZ, Zuccaro E, Genovese G, Loboda AA, Neumann A, Lilliehook C, Kuismin O, Hamalainen E, Kurki M, Hultman CM, Kähler AK, Paulo JA, Ganna A, Madison J, Cohen B, McPhie D, Adolfsson R, Perlis R, Dolmetsch R, Farhi S, McCarroll S, Hyman S, Neale B, Barrett LE, Harper W, Palotie A, Daly M, Eggan K.
Nat Commun
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Quantitative proteomics reveals the selectivity of ubiquitin-binding autophagy receptors in the turnover of damaged lysosomes by lysophagy.
Authors: Authors: Eapen VV, Swarup S, Hoyer MJ, Paulo JA, Harper JW.
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Cullin-RING Ubiquitin Ligase Regulatory Circuits: A Quarter Century Beyond the F-Box Hypothesis.
Authors: Authors: Harper JW, Schulman BA.
Annu Rev Biochem
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Quantitative intravital imaging in zebrafish reveals in vivo dynamics of physiological-stress-induced mitophagy.
Authors: Authors: <a href="https://connects.catalyst.harvard.edu/Profiles/profile/60559335">Wrighton PJ</a>, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/70671808">Shwartz A</a>, Heo JM, Quenzer ED, LaBella KA, Harper JW, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1237905">Goessling W</a>.
J Cell Sci
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The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase.
Authors: Authors: McKenna MJ, Sim SI, Ordureau A, Wei L, Harper JW, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/64697192">Shao S</a>, Park E.
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EDF1 coordinates cellular responses to ribosome collisions.
Authors: Authors: Sinha NK, Ordureau A, Best K, Saba JA, Zinshteyn B, Sundaramoorthy E, Fulzele A, Garshott DM, Denk T, Thoms M, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1231877">Paulo JA</a>, Harper JW, Bennett EJ, Beckmann R, Green R.
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Systematic quantitative analysis of ribosome inventory during nutrient stress.
Authors: Authors: An H, Ordureau A, Körner M, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1231877">Paulo JA</a>, Harper JW.
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Inhibition of sphingolipid synthesis improves outcomes and survival in GARP mutant wobbler mice, a model of motor neuron degeneration.
Authors: Authors: Petit CS, Lee JJ, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/123145846">Boland S</a>, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/32571414">Swarup S</a>, Christiano R, Lai ZW, Mejhert N, Elliott SD, McFall D, Haque S, Huang EJ, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1242114">Bronson RT</a>, Harper JW, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/29624598">Farese RV</a>, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/29624596">Walther TC</a>.
Proc Natl Acad Sci U S A
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Global Landscape and Dynamics of Parkin and USP30-Dependent Ubiquitylomes in iNeurons during Mitophagic Signaling.
Authors: Authors: Ordureau A, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1231877">Paulo JA</a>, Zhang J, An H, Swatek KN, Cannon JR, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/68650938">Wan Q</a>, Komander D, Harper JW.
Mol Cell
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Pathogenic Pathways in Early-Onset Autosomal Recessive Parkinson's Disease Discovered Using Isogenic Human Dopaminergic Neurons.
Authors: Authors: <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1230786">Ahfeldt T</a>, Ordureau A, Bell C, Sarrafha L, Sun C, Piccinotti S, Grass T, Parfitt GM, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1231877">Paulo JA</a>, Yanagawa F, Uozumi T, Kiyota Y, Harper JW, <a href="https://connects.catalyst.harvard.edu/Profiles/profile/1230753">Rubin LL</a>.
Stem Cell Reports
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