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

The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.
Authors: Authors: Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW.
Genes Dev
View full abstract on Pubmed
Interaction between cyclin-dependent kinases and human papillomavirus replication-initiation protein E1 is required for efficient viral replication.
Authors: Authors: Ma T, Zou N, Lin BY, Chow LT, Harper JW.
Proc Natl Acad Sci U S A
View full abstract on Pubmed
p21(CIP1) and p57(KIP2) control muscle differentiation at the myogenin step.
Authors: Authors: Zhang P, Wong C, Liu D, Finegold M, Harper JW, Elledge SJ.
Genes Dev
View full abstract on Pubmed
Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of tissue growth and development.
Authors: Authors: Zhang P, Wong C, DePinho RA, Harper JW, Elledge SJ.
Genes Dev
View full abstract on Pubmed
G1 cyclin-dependent kinases are sufficient to initiate DNA synthesis in quiescent human fibroblasts.
Authors: Authors: Connell-Crowley L, Elledge SJ, Harper JW.
Curr Biol
View full abstract on Pubmed
F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex.
Authors: Authors: Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW.
Cell
View full abstract on Pubmed
S-Phase entry upon ectopic expression of G1 cyclin-dependent kinases in the absence of retinoblastoma protein phosphorylation.
Authors: Authors: Leng X, Connell-Crowley L, Goodrich D, Harper JW.
Curr Biol
View full abstract on Pubmed
Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome.
Authors: Authors: Zhang P, Liégeois NJ, Wong C, Finegold M, Hou H, Thompson JC, Silverman A, Harper JW, DePinho RA, Elledge SJ.
Nature
View full abstract on Pubmed
SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.
Authors: Authors: Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ.
Cell
View full abstract on Pubmed
Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4.
Authors: Authors: Stepanova L, Leng X, Parker SB, Harper JW.
Genes Dev
View full abstract on Pubmed