Area of research
Molecular Biology · Oncology
Research interest
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.
Proximity-specific ribosome profiling reveals the logic of localized mitochondrial translation
Multimodal cell maps as a foundation for structural and functional genomics
EndoMAP.v1 charts the structural landscape of human early endosome complexes
ARMC1 partitions between distinct complexes and assembles MIRO with MTFR to control mitochondrial distribution
Publisher Correction: Multimodal cell maps as a foundation for structural and functional genomics
UFM1 E3 ligase promotes recycling of 60S ribosomal subunits from the ER
IRGQ-mediated autophagy in MHC class I quality control promotes tumor immune evasion
Principles of paralog-specific targeted protein degradation engaging the C-degron E3 KLHDC2
Structural basis for C-degron selectivity across KLHDCX family E3 ubiquitin ligases
Abstract 2348: A global multiscale map of protein assemblies from integration of protein interactions and images
Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis
The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia
Targeted protein degradation: from small molecules to complex organelles—a Keystone Symposia report
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
Cullin-RING Ubiquitin Ligase Regulatory Circuits: A Quarter Century Beyond the F-Box Hypothesis
Temporal proteomics during neurogenesis reveals large-scale proteome and organelle remodeling via selective autophagy
A multi-scale map of cell structure fusing protein images and interactions
iRQC, a surveillance pathway for 40S ribosomal quality control during mRNA translation initiation
ORF10–Cullin-2–ZYG11B complex is not required for SARS-CoV-2 infection
EDF1 coordinates cellular responses to ribosome collisions
Inhibition of sphingolipid synthesis improves outcomes and survival in GARP mutant <i>wobbler</i> mice, a model of motor neuron degeneration
Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence
Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies
TEX264 Is an Endoplasmic Reticulum-Resident ATG8-Interacting Protein Critical for ER Remodeling during Nutrient Stress
Probing the Global Cellular Responses to Lipotoxicity Caused by Saturated Fatty Acids
A glycine-specific N-degron pathway mediates the quality control of protein <i>N</i> -myristoylation
Hook3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein-1 and KIF1C
Integrated proteogenetic analysis reveals the landscape of a mitochondrial-autophagosome synapse during PARK2-dependent mitophagy
ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection
NCOA4 maintains murine erythropoiesis via cell autonomous and non-autonomous mechanisms