J. A. Wells

Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α

The paper uses chemoproteomics to identify immunogenic cell surface substrates of CK2α in the tumor microenvironment, showing that extracellular phosphorylation can generate immunogenic antigens.

PVRL2 Suppresses Anti-tumor Immunity Through PVRIG- and TIGIT-Independent Pathways

This study shows PVRL2 suppresses anti-tumor immunity independently of PVRIG and TIGIT, with deletion reducing tumor growth more than PD-L1 loss.

Multi-scale photocatalytic proximity labeling reveals cell surface neighbors on and between cells

The paper introduces a multi-scale proximity labeling method using Eosin Y to map cell surface protein neighborhoods at varying resolutions and validates interactions of EGFR and CAR-T cell synapses.

Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma

The paper identifies tumor-specific alternative splicing events in glioma that could generate cell-surface antigens but finds significant spatiotemporal heterogeneity and lack of proteomic evidence.

Site-specific proximity labeling at single residue resolution for identification of protein partners in vitro and on cells

This paper optimizes a high-resolution proximity labeling method to identify protein partners of HER2 on cells and in vitro, finding 20 high-confidence neighbors enriched compared to non-specific labeling.

Secreted HLA Fc-Fusion Profiles Immunopeptidome in Hypoxic PDAC and Cellular Senescence

This paper introduces a novel sHLA Fc-fusion method to identify HLA-associated peptides in hypoxic PDAC and senescence, revealing >30,000 unique peptides, many previously unreported.

A general approach for selection of epitope-directed binders to proteins

This paper introduces a method to select antibodies targeting specific epitopes on proteins by using a decoy antigen and alternating selection rounds, demonstrating its effectiveness with five different antigens.

Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps

The paper develops a computational pipeline combining Rosetta and cryo-EM to analyze ACE2 receptor traps' binding to SARS-CoV-2 variants, showing high affinity and neutralization capabilities against Omicron and Delta.

MEK inhibition enhances presentation of targetable MHC-I tumor antigens in mutant melanomas

This study shows MEK inhibition increases MHC-I antigen presentation in melanoma, enhancing immunotherapy efficacy through targeted epitopes.

Cell-surface tethered promiscuous biotinylators enable small-scale surface proteomics of human exosomes

This paper introduces two methods for rapid, small-scale cell surface biotinylation using tethered enzymes, enabling surface proteome analysis of cells and exosomes with high coverage and quantification of 1,020 surface proteins.

Precision engineering of an anti-HLA-A2 chimeric antigen receptor in regulatory T cells for transplant immune tolerance

This paper develops an anti-HLA-A2 CAR for Tregs to induce transplant tolerance, showing they target HLA-A2-expressing grafts and suppress immune rejection.

CUB domain containing protein 1 (CDPC1) is a target for radioligand therapy in castration resistant prostate cancer

This paper evaluates CDCP1 as a target for radioligand therapy in mCRPC, showing its expression in most biopsies and demonstrating antitumor effects with 177Lu-4A06.

Targeting a proteolytic neo-epitope of CUB-domain containing protein 1 in RAS-driven cancer

The paper develops antibodies targeting proteolytic neo-epitopes of CDCP1 in RAS-driven cancers, showing improved tumor specificity and safety.

Hypoxia is a dominant remodeler of the CD8+ T cell surface proteome relative to activation and regulatory T cell-mediated suppression

This study compares how hypoxia and regulatory T cells affect the CD8+ T cell surface proteome, finding hypoxia has a more significant impact than Treg-mediated suppression.

BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2

This study identifies BRD2 as a regulator of ACE2 transcription and shows that BRD2 inhibitors block SARS-CoV-2 infection in human cells and animal models.

Defining the cell surface proteomic landscape of multiple myeloma reveals immunotherapeutic strategies and biomarkers of drug resistance

This study defines the myeloma cell surface proteome, identifies therapeutic targets and resistance biomarkers, and presents a miniaturized surface proteomics protocol.

The CD28-transmembrane domain mediates chimeric antigen receptor heterodimerization with CD28

This paper shows that CD28-TMD in CARs forms heterodimers with endogenous CD28, affecting T-cell responses and surface expression.

Bi-paratopic and multivalent human VH domains neutralize SARS-CoV-2 by targeting distinct epitopes within the ACE2 binding interface of Spike

This paper identifies and engineers multivalent human VH domains that neutralize SARS-CoV-2 by targeting distinct epitopes on the Spike protein's ACE2 binding interface, showing increased affinity and potency.

Engineered ACE2 receptor traps potently neutralize SARS-CoV-2

This paper describes engineered ACE2 receptor traps that potently neutralize SARS-CoV-2 by blocking viral entry through enhanced binding affinity.

Trimeric SARS-CoV-2 Spike interacts with dimeric ACE2 with limited intra-Spike avidity

This study investigates the interaction between SARS-CoV-2 Spike and ACE2, showing that dimeric ACE2 binds with high affinity to Spike and blocks viral entry, with limited intra-Spike avidity.

Deep profiling of protease substrate specificity enabled by dual random and scanned human proteome substrate phage libraries

This paper introduces SPD-NGS, a method using phage display libraries to deeply profile protease substrate specificity, identifying cleavage sites and natural substrates with high coverage and accuracy.

Mapping proteolytic neo-N termini at the surface of living cells

The paper develops a method to capture and sequence cell surface N termini in live cells, revealing changes in neo-N termini abundance in response to proteolytic stimuli.

Broad and thematic remodeling of the surface glycoproteome on isogenic cells transformed with driving proliferative oncogenes

This study uses proteomics to show how six oncogenes remodel the surface glycoproteome of breast cells, with common functional themes reversed by MEK inhibition.

Systematic identification of engineered methionines and oxaziridines for efficient, stable, and site-specific antibody bioconjugation

This study systematically identifies engineered methionines and oxaziridines for efficient, stable, and site-specific antibody bioconjugation, finding stable sulfimide modifications comparable to cysteine-maleimide conjugation.

New routes for PTP1B allosteric inhibition by multitemperature crystallography, fragment screening and covalent tethering

The paper identifies a new allosteric site in PTP1B using multitemperature crystallography and fragment screening, showing covalent tethering can inhibit enzyme activity.

Time-resolved proteomics vs. ribosome profiling reveals translation dynamics under stress

The paper compares time-resolved proteomics and ribosome profiling to study translation dynamics under stress in multiple myeloma cells treated with bortezomib.