James A. Wells
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View article: Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap
Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap Open
Photoproximity labeling proteomics (PLP) methods have recently shown that cell surface receptors can form lateral interactome networks. Here, we present a paired set of PLP workflows that dynamically track neighborhood changes for oncogeni…
View article: Hijacking Extracellular Targeted Protein Degrader–Drug Conjugates for Enhanced Drug Delivery
Hijacking Extracellular Targeted Protein Degrader–Drug Conjugates for Enhanced Drug Delivery Open
Antibody-based therapeutics encompass diverse modalities for targeting tumor cells. Among these, antibody-drug conjugates (ADCs) and extracellular targeted protein degradation (eTPD) specifically depend on efficient lysosomal trafficking f…
View article: A cytokine receptor-targeting chimera (kineTAC) toolbox for expanding extracellular targeted protein degradation
A cytokine receptor-targeting chimera (kineTAC) toolbox for expanding extracellular targeted protein degradation Open
Extracellular targeted protein degradation (eTPD) is as an important new modality for manipulating the extracellular proteome. However, most eTPD receptors are expressed broadly or are restricted to the liver. Cytokine receptor targeting c…
View article: β-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity
β-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity Open
To define how Aβ pathology alters microglia function in Alzheimer’s disease, we profiled the microglia surfaceome following treatment with Aβ fibrils. Our findings reveal that Aβ-associated human microglia upregulate Glypican 4 (GPC4), a G…
View article: Low-density lipoprotein receptor-targeting chimeras for membrane protein degradation and enhanced drug delivery
Low-density lipoprotein receptor-targeting chimeras for membrane protein degradation and enhanced drug delivery Open
Antibody-based therapeutics encompass diverse modalities for targeting tumor cells. Among these, antibody-drug conjugates (ADCs) and extracellular targeted protein degradation (eTPD) specifically depend on efficient lysosomal trafficking f…
View article: High-affinity CD16A polymorphism associated with reduced risk ofsevere COVID-19
High-affinity CD16A polymorphism associated with reduced risk ofsevere COVID-19 Open
CD16A is an activating Fc receptor on NK cells that mediates antibody-dependent cellular cytotoxicity (ADCC), a key mechanism in antiviral immunity. However, the role of NK cell-mediated ADCC in SARS-CoV-2 infection remains unclear, partic…
View article: Hypoxia Induces Extensive Protein and Proteolytic Remodeling of the Cell Surface in Pancreatic Adenocarcinoma (PDAC) Cell Lines
Hypoxia Induces Extensive Protein and Proteolytic Remodeling of the Cell Surface in Pancreatic Adenocarcinoma (PDAC) Cell Lines Open
The tumor microenvironment (TME) plays a crucial role in cancer progression. Hypoxia is a hallmark of the TME and induces a cascade of molecular events that affect cellular processes involved in metabolism, metastasis, and proteolysis. In …
View article: CRISPRi-based screen of autism spectrum disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning
CRISPRi-based screen of autism spectrum disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning Open
Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with complex biology. The identification of ASD risk genes from exome-wide association studies and de novo variation analyses has enabled mechanistic investigations …
View article: Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome
Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome Open
The cell surface proteome, or surfaceome, is the hub for cells to interact and communicate with the outside world. Many disease-associated changes are hard-wired within the surfaceome, yet approved drugs target less than 50 cell surface pr…
View article: β-Amyloid Induces Microglial Expression of GPC4 and APOE Leading to Increased Neuronal Tau Pathology and Toxicity
β-Amyloid Induces Microglial Expression of GPC4 and APOE Leading to Increased Neuronal Tau Pathology and Toxicity Open
SUMMARY To elucidate the impact of Aβ pathology on microglia in Alzheimer’s disease pathogenesis, we profiled the microglia surfaceome following treatment with Aβ fibrils. Our findings reveal that Aβ-associated human microglia upregulate G…
View article: Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture
Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture Open
Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndro…
View article: Mechanism-guided engineering of a minimal biological particle for genome editing
Mechanism-guided engineering of a minimal biological particle for genome editing Open
The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packagi…
View article: Spatiotemporal photocatalytic proximity labeling proteomics reveals ligand-activated extracellular and intracellular EGFR neighborhoods
Spatiotemporal photocatalytic proximity labeling proteomics reveals ligand-activated extracellular and intracellular EGFR neighborhoods Open
Photo-proximity labeling proteomics (PLP) methods have recently shown that the cell surface receptors can dynamically form lateral interactome networks. Here, we present a paired set of PLP workflows that simultaneously track neighborhood …
View article: Hypoxia induces extensive protein and proteolytic remodeling of the cell surface in pancreatic adenocarcinoma (PDAC) cell lines
Hypoxia induces extensive protein and proteolytic remodeling of the cell surface in pancreatic adenocarcinoma (PDAC) cell lines Open
The tumor microenvironment (TME) plays a crucial role in cancer progression. Hypoxia is a hallmark of the TME and induces a cascade of molecular events that affects cellular processes involved in metabolism, metastasis, and proteolysis. In…
View article: <i>De novo</i>design of proteins that bind naphthalenediimides, powerful photooxidants with tunable photophysical properties
<i>De novo</i>design of proteins that bind naphthalenediimides, powerful photooxidants with tunable photophysical properties Open
De novo protein design provides a framework to test our understanding of protein function and to build proteins with cofactors and functions not found in nature. Here, we report the design of proteins designed to bind powerful photooxidant…
View article: Mechanism-guided engineering of a minimal biological particle for genome editing
Mechanism-guided engineering of a minimal biological particle for genome editing Open
The widespread application of genome editing to treat or even cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped Delivery Vehicles (EDVs) are engineered virally-derived particles capable of pac…
View article: Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency
Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency Open
Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not a…
View article: CRISPRi-based screen of Autism Spectrum Disorder risk genes in microglia uncovers roles of<i>ADNP</i>in microglia endocytosis and synaptic pruning
CRISPRi-based screen of Autism Spectrum Disorder risk genes in microglia uncovers roles of<i>ADNP</i>in microglia endocytosis and synaptic pruning Open
Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with complex biology. The identification of ASD risk genes from exome-wide association studies and de novo variation analyses has enabled mechanistic investigations …
View article: Figure S1 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Figure S1 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Supplementary Figure S1: Proteomic analysis identifies PVRL2 on tumor-derived exosomes.
View article: Figure S2 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Figure S2 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Supplementary Figure S2: PVRL2 promotes tumor growth through an immune-dependent mechanism.
View article: Figure S5 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Figure S5 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Supplementary Figure S5: Combined loss of PVRL2 and PVR loss does not further inhibit tumor growth.
View article: Table S1 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Table S1 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Supplementary Table S1: Statistical analysis comparing the areas under curves (AUC) of tumor growth data between groups using an unpaired Student’s t test.
View article: Figure S3 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Figure S3 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Supplementary Figure S3: PVRL2 regulates CD8 T cell and NK cell activation.
View article: Figure S1 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Figure S1 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Supplementary Figure S1: Proteomic analysis identifies PVRL2 on tumor-derived exosomes.
View article: Data from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Data from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Poliovirus receptor-related 2 (PVRL2, also known as nectin-2 or CD112) is believed to act as an immune checkpoint protein in cancer; however, most insight into its role is inferred from studies on its known receptor, poliovirus receptor (P…
View article: Figure S3 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Figure S3 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Supplementary Figure S3: PVRL2 regulates CD8 T cell and NK cell activation.
View article: Data from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Data from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Poliovirus receptor-related 2 (PVRL2, also known as nectin-2 or CD112) is believed to act as an immune checkpoint protein in cancer; however, most insight into its role is inferred from studies on its known receptor, poliovirus receptor (P…
View article: Table S1 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways
Table S1 from PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Open
Supplementary Table S1: Statistical analysis comparing the areas under curves (AUC) of tumor growth data between groups using an unpaired Student’s t test.