Scholars@Duke
Joshua Clair Snyder

Joshua Clair Snyder

Adjunct Professor in the Department of Surgery
Surgery, Surgical Sciences
203 Research Drive, MSRB1 475A, DUMC 2606, Durham, NC 27710
MSRBI Rm 475A, Durham, NC 27710

Scholarly Works - Journal articles

β-Arrestin condensates regulate G-protein-coupled receptor function.

Journal article Nature · July 2026 β-Arrestins 1 and 2 are multifunctional adaptor proteins1 that regulate the signalling of G-protein-coupled receptors (GPCRs), the largest class of receptors, which impact nearly all aspects of physiology and are one of the most common drug targets2. Altho ... Full text Link to item Cite

Precision preclinical modeling to advance cancer treatment.

Journal article J Natl Cancer Inst · April 1, 2025 A new era of cancer management is underway in which treatments are being developed for the entire continuum of the disease process. The availability of genetically engineered and naturally occurring preclinical models serves as instructive platforms for ev ... Full text Link to item Cite

Nonlinear progression during the occult transition establishes cancer lethality.

Journal article Dis Model Mech · March 1, 2025 Cancer screening relies upon a linear model of neoplastic growth and progression. Yet, historical observations suggest that malignant progression is uncoupled from growth, which may explain the paradoxical increase in early-stage breast cancer detection wi ... Full text Open Access Link to item Cite

Adaptive selection of p53 mutation metaplastic phenotypes in estrogen-independent progression of ER+ tumors: A mechanism for acquired resistance to hormonal therapy.

Journal article bioRxiv · February 6, 2025 Estrogen receptor positive (ER + ) subtypes of mammary adenocarcinoma comprise 79% of all breast cancer diagnosis and 67% of all breast cancer mortality. The paucity of models of ER + mammary cancer that mimic human disease and response to treatment has li ... Full text Link to item Cite

Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent "NoGlow" Mice.

Journal article Cancer Res Commun · April 9, 2024 UNLABELLED: The ability to temporally regulate gene expression and track labeled cells makes animal models powerful biomedical tools. However, sudden expression of xenobiotic genes [e.g., GFP, luciferase (Luc), or rtTA3] can trigger inadvertent immunity th ... Full text Link to item Cite

Membrane structure and internalization dynamics of human Flower isoforms hFWE3 and hFWE4 indicate a conserved endocytic role for hFWE4.

Journal article J Biol Chem · August 2023 Human Flower (hFWE) isoforms hFWE1-4 are putative transmembrane (TM) proteins that reportedly mediate fitness comparisons during cell competition through extracellular display of their C-terminal tails. Isoform topology, subcellular localization, and durat ... Full text Link to item Cite

A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease.

Journal article FASEB J · June 2023 Intestinal epithelial stem cells (ISCs) are responsible for intestinal epithelial barrier renewal; thereby, ISCs play a critical role in intestinal pathophysiology research. While transgenic ISC reporter mice are available, advanced translational studies l ... Full text Link to item Cite

Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation.

Journal article Cell Syst · April 19, 2023 Collective cell behavior contributes to all stages of cancer progression. Understanding how collective behavior emerges through cell-cell interactions and decision-making will advance our understanding of cancer biology and provide new therapeutic approach ... Full text Link to item Cite

The use of histotripsy as intratumoral immunotherapy beyond tissue ablation-the rationale for exploring the immune effects of histotripsy.

Journal article Int J Hyperthermia · 2023 Mechanical high-intensity focused ultrasound (M-HIFU), which includes histotripsy, is a non-ionizing, non-thermal ablation technology that can be delivered by noninvasive methods. Because acoustic cavitation is the primary mechanism of tissue disruption, h ... Full text Link to item Cite

Veterinary Management of Harderian Gland Tumors in Cancer Rainbow (crainbow) HER2-Positive Mice.

Journal article Comp Med · December 1, 2022 A Cancer Rainbow mouse line that expresses 3 fluorescently labeled isoforms of the tumor-driver gene HER2 (HER2BOW) was developed recently for the study of tumorigenesis in the mammary gland. The expression of 1 of the 3 HER2 isoforms in HER2BOW mice is in ... Full text Link to item Cite

HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study.

Journal article Mol Cancer Ther · January 2022 A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of n ... Full text Link to item Cite

Combination of ultrasound-based mechanical disruption of tumor with immune checkpoint blockade modifies tumor microenvironment and augments systemic antitumor immunity.

Journal article J Immunother Cancer · January 2022 BACKGROUND: Despite multimodal adjuvant management with radiotherapy, chemotherapy and hormonal therapies, most surgically resected primary breast cancers relapse or metastasize. A potential solution to late and distant recurrence is to augment systemic an ... Full text Link to item Cite

Measuring Nonapoptotic Caspase Activity with a Transgenic Reporter in Mice.

Journal article eNeuro · 2022 The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or n ... Full text Link to item Cite

HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase.

Journal article Mol Cancer Res · October 2021 HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the in ... Full text Link to item Cite

Noncanonical scaffolding of Gαi and β-arrestin by G protein-coupled receptors.

Journal article Science · March 12, 2021 Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific Gα protein subtypes and β-arrestin adaptor proteins. G protein-mediated signaling and β-arrestin-mediated sig ... Full text Link to item Cite

Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.

Journal article Clin Cancer Res · September 1, 2020 PURPOSE: Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we h ... Full text Link to item Cite

Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors.

Journal article Commun Biol · May 8, 2020 Photodynamic therapy (PDT) ablates malignancies by applying focused near-infrared (nIR) light onto a lesion of interest after systemic administration of a photosensitizer (PS); however, the accumulation of existing PS is not tumor-exclusive. We developed a ... Full text Link to item Cite

A cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion.

Journal article Nat Commun · December 2, 2019 Field cancerization is a premalignant process marked by clones of oncogenic mutations spreading through the epithelium. The timescales of intestinal field cancerization can be variable and the mechanisms driving the rapid spread of oncogenic clones are unk ... Full text Link to item Cite

Slow-release delivery enhances the pharmacological properties of oral 5-hydroxytryptophan: mouse proof-of-concept.

Journal article Neuropsychopharmacology · November 2019 5-hydroxytryptophan (5-HTP) has shown therapeutic promise in a range of human CNS disorders. But native 5-HTP immediate release (IR) is poorly druggable, as rapid absorption causes rapid onset of adverse events, and rapid elimination causes fluctuating exp ... Full text Link to item Cite

Vaccine-Induced Memory CD8+ T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study.

Journal article Clin Cancer Res · May 1, 2019 PURPOSE: Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines targeting established oncogenic dr ... Full text Open Access Link to item Cite

hCALCRL mutation causes autosomal recessive nonimmune hydrops fetalis with lymphatic dysplasia.

Journal article J Exp Med · September 3, 2018 We report the first case of nonimmune hydrops fetalis (NIHF) associated with a recessive, in-frame deletion of V205 in the G protein-coupled receptor, Calcitonin Receptor-Like Receptor (hCALCRL). Homozygosity results in fetal demise from hydrops fetalis, w ... Full text Link to item Cite

Inhibiting clathrin-mediated endocytosis of the leucine-rich G protein-coupled receptor-5 diminishes cell fitness.

Journal article J Biol Chem · April 28, 2017 The leucine-rich G protein-coupled receptor-5 (LGR5) is expressed in adult tissue stem cells of many epithelia, and its overexpression is negatively correlated with cancer prognosis. LGR5 potentiates WNT/β-catenin signaling through its unique constitutive ... Full text Link to item Cite

Distinct cortical and striatal actions of a β-arrestin-biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties.

Journal article Proc Natl Acad Sci U S A · December 13, 2016 The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they ... Full text Link to item Cite

Chapter One - Ubiquitination and Deubiquitination of G Protein-Coupled Receptors.

Journal article Prog Mol Biol Transl Sci · 2016 The seven-transmembrane containing G protein-coupled receptors (GPCRs) constitute the largest family of cell-surface receptors. Transmembrane signaling by GPCRs is fundamental to many aspects of physiology including vision, olfaction, cardiovascular, and r ... Full text Link to item Cite

A rapid and affordable screening platform for membrane protein trafficking.

Journal article BMC Biol · December 17, 2015 BACKGROUND: Membrane proteins regulate a diversity of physiological processes and are the most successful class of targets in drug discovery. However, the number of targets adequately explored in chemical space and the limited resources available for scree ... Full text Link to item Cite

Lgr4 and Lgr5 drive the formation of long actin-rich cytoneme-like membrane protrusions.

Journal article J Cell Sci · March 15, 2015 Embryonic development and adult tissue homeostasis require precise information exchange between cells and their microenvironment to coordinate cell behavior. A specialized class of ultra-long actin-rich filopodia, termed cytonemes, provides one mechanism f ... Full text Link to item Cite

The complete mitochondrial genome sequence of the Canada goose (Branta canadensis).

Journal article Mitochondrial DNA · 2015 The Canada goose (Branta canadensis) entire mitochondrial genome of a bird from Western Pennsylvania has 16,760 bp (GenBank accession number NC 007011) and has been analyzed for gene locations, length, start codon and stop codons. This genome from a bird h ... Full text Link to item Cite

Triphenylmethane dye activation of beta-arrestin.

Journal article Biochemistry · August 13, 2013 β-Arrestins regulate G protein-coupled receptor signaling as competitive inhibitors and protein adaptors. Low molecular weight biased ligands that bind receptors and discriminate between the G protein dependent arm and β-arrestin, clathrin-associated arm o ... Full text Link to item Cite

Constitutive internalization of the leucine-rich G protein-coupled receptor-5 (LGR5) to the trans-Golgi network.

Journal article J Biol Chem · April 12, 2013 LGR5 is a Wnt pathway associated G protein-coupled receptor (GPCR) that serves as a molecular determinant of stem cells in numerous tissues including the intestine, stomach, hair follicle, eye, and mammary gland. Despite its importance as a marker for this ... Full text Link to item Cite

The stem cell-expressed receptor Lgr5 possesses canonical and functionally active molecular determinants critical to β-arrestin-2 recruitment.

Journal article PLoS One · 2013 Lgr5 is a membrane protein related to G protein-coupled receptors (GPCR)s whose expression identifies stem cells in multiple tissues and is strongly correlated with cancer. Despite the recent identification of endogenous ligands for Lgr5, its mode of signa ... Full text Link to item Cite

Deletion of GSK3β in D2R-expressing neurons reveals distinct roles for β-arrestin signaling in antipsychotic and lithium action.

Journal article Proc Natl Acad Sci U S A · December 11, 2012 Several studies in rodent models have shown that glycogen synthase kinase 3 β (GSK3β) plays an important role in the actions of antispychotics and mood stabilizers. Recently it was demonstrated that GSK3β through a β-arrestin2/protein kinase B (PKB or Akt) ... Full text Link to item Cite

β-Catenin-SOX2 signaling regulates the fate of developing airway epithelium.

Journal article J Cell Sci · February 15, 2012 Wnt-β-catenin signaling regulates cell fate during organ development and postnatal tissue maintenance, but its contribution to specification of distinct lung epithelial lineages is still unclear. To address this question, we used a Cre recombinase (Cre)-Lo ... Full text Link to item Cite

Clara cells attenuate the inflammatory response through regulation of macrophage behavior.

Journal article Am J Respir Cell Mol Biol · February 2010 Chronic lung diseases are marked by excessive inflammation and epithelial remodeling. Reduced Clara cell secretory function and corresponding decreases in the abundance of the major Clara cell secretory protein (CCSP) are characteristically seen in these d ... Full text Link to item Cite

Stem cells are dispensable for lung homeostasis but restore airways after injury.

Journal article Proc Natl Acad Sci U S A · June 9, 2009 Local tissue stem cells have been described in airways of the lung but their contribution to normal epithelial maintenance is currently unknown. We therefore developed aggregation chimera mice and a whole-lung imaging method to determine the relative contr ... Full text Link to item Cite

Reparative capacity of airway epithelium impacts deposition and remodeling of extracellular matrix.

Journal article Am J Respir Cell Mol Biol · June 2009 Defective epithelial repair in the setting of chronic lung disease has been suggested to contribute to uncontrolled extracellular matrix (ECM) deposition and development of fibrosis. We sought to directly test this hypothesis through gene expression profil ... Full text Link to item Cite

Molecular staging of epithelial maturation using secretory cell-specific genes as markers.

Journal article Am J Respir Cell Mol Biol · March 2009 Bronchiolar Clara cells undergo phenotypic changes during development and in disease. These changes are poorly described due to a paucity of molecular markers. We used chemical and transgenic approaches to ablate Clara cells, allowing identification of the ... Full text Link to item Cite

Endogenous lung stem cells and contribution to disease.

Journal article J Pathol · January 2009 Epithelial branching during the process of lung development results in the establishment of distinct functional zones, each of which is characterized by a unique cellular composition and repertoire of local progenitor cells. Significant new insights into c ... Full text Link to item Cite

CCSP regulates cross talk between secretory cells and both ciliated cells and macrophages of the conducting airway.

Journal article Am J Physiol Lung Cell Mol Physiol · July 2007 Pulmonary host defense employs a combination of biochemical and biophysical activities to recognize, inactivate, and mediate clearance of environmental agents as well as modulate the overall response to such challenge. Dysregulation of the inflammatory arm ... Full text Link to item Cite