J. Wade Harper

GolgiFold: A Structural Predictome of Human Golgi Protein Complexes

The paper develops GolgiFold, a structure-based PPI map of human Golgi proteins, identifying over 1,800 interactions and confirming new protein contacts through experimental validation.

Failure to release from the ER translocon induces 60S ribosome degradation

The paper identifies a cell-state-dependent pathway for degrading ER-retained 60S ribosomal subunits through UFMylation loss and the action of TLSD1.

The BAF complex works with FOS to regulate human neuronal activity-dependent ASD-associated gene programs

This study identifies BAF complex interaction with FOS in regulating ASD-associated gene programs through enhancer activation and shows how genetic variants disrupt this process.

Components of an ESCRT-independent nuclear envelope assembly pathway

In S. japonicus, the ESCRT adaptor Alx1 activates the essential PH-domain protein Vid27 through interaction, driving postmitotic nuclear envelope sealing independently of Cmp7 and ESCRT-III.

Structural Mechanisms of DNAJC13 Dimeric Assembly and InsP6 binding in Recycling Endosome Regulation

Cryo-EM at 2.4 Å shows DNAJC13 as an antiparallel arch-shaped homodimer with a buried InsP6 pocket; dimerization controls WASH recruitment, tubule fission, and melanin production.

A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical and dopaminergic-like induced neurons

The paper develops a human stem cell toolkit for studying lysosomal storage disorders by generating proteomic data from induced cortical and dopaminergic-like neurons.

Structural basis for regulation of the proteasome 20S core particle by the Parkinsonism-associated proteins FBXO7 and PI31

This study reveals how FBXO7 and PI31 regulate the proteasome 20S core particle and how disease variants disrupt this function.

Organelle bridges and nanodomain partitioning govern targeting of membrane-embedded proteins to lipid droplets

The paper shows that LD-targeted proteins are confined by nanodomains and transported via ER-LD bridges, revealing mechanisms for their selective accumulation on lipid droplets.

Cathepsin-dependent amyloid formation drives mechanical rupture of lysosomal membranes

This study shows that LLOMe forms amyloid structures inside lysosomes that mechanically rupture the lysosomal membrane, revealing a structural mechanism for lysosomal damage.

Machine Learning enables efficient and effective affinity maturation of nanobodies

This paper uses machine learning to predict high-affinity nanobody binders from sparse sequencing data, outperforming deep learning and semi-supervised methods with linear models.

Mapping the functional importance of site-specific ubiquitination across the human proteome

The paper maps the functional importance of site-specific ubiquitination across the human proteome by analyzing conservation, perturbation, and machine learning scores.

Alpha-Synuclein aggregates inhibit ESCRT-III through sequestration and collateral degradation

This study shows that alpha-synuclein fibrils sequester and degrade ESCRT-III proteins, leading to endolysosomal damage and increased alpha-synuclein aggregation.

EndoMAPV1, a Structural Protein Complex Landscape of Human Endosomes

The paper creates a structural interactome of human endosomes using cross-linking, mass spectrometry, and AlphaFold, identifying structural models for endosomal protein complexes.

Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways

This study identifies UBE3C and NRF1-dependent proteasomal pathways that regulate acute protein aggregate turnover in response to misfolded protein accumulation.

Endo-IP and Lyso-IP Toolkit for Endolysosomal Profiling of Human Induced Neurons

This paper develops Endo-IP and Lyso-IP methods to profile endolysosomal proteins in induced neurons, revealing cargo and machinery involved in neurodegenerative disease.

Spatiotemporal proteomic profiling of cellular responses to NLRP3 agonists

This study profiles proteomic changes in subcellular compartments during NLRP3 inflammasome activation and identifies disruptions in retrograde trafficking pathways.

Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models

This study identifies MTK458, a PINK1 activator, which reduces α-synuclein pathology and pUb levels in Parkinson's disease models and correlates plasma pUb with disease progression.

Proteomics analysis of autophagy cargos reveals distinct adaptations in PINK1 and LRRK2 models of Parkinson disease

The paper uses proteomics to compare autophagy cargos in two Parkinson disease mouse models, finding distinct adaptive pathways in PINK1 and LRRK2 models.

The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia

This study investigates how the 22q11.2 deletion affects gene expression in neural progenitor cells and neurons, linking it to schizophrenia risk through altered presynaptic gene products.

Mapping cell structure across scales by fusing protein images and interactions

The paper integrates protein imaging and interaction data to create a unified map of eukaryotic cell structure, revealing new subcellular systems and protein associations.

Dual Proteome-scale Networks Reveal Cell-specific Remodeling of the Human Interactome

The paper creates two large-scale cell-line-specific human interactomes using affinity-purification mass spectrometry and identifies shared and cell-specific protein interactions.