Publications and Funding
Featured Publications
Cell Reports, 2023
PSGL-1 (P-selectin glycoprotein-1) is a T cell-intrinsic checkpoint regulator of exhaustion with an unknown mechanism of action. Here, we show that PSGL-1 acts upstream of PD-1 and requires co-ligation with the T cell receptor (TCR) to attenuate activation of mouse and human CD8+ T cells and drive terminal T cell exhaustion. PSGL-1 directly restrains TCR signaling via Zap70 and maintains expression of the Zap70 inhibitor Sts-1. PSGL-1 deficiency empowers CD8+ T cells to respond to low-affinity TCR ligands and inhibit growth of PD-1-blockade-resistant melanoma by enabling tumor-infiltrating T cells to sustain an elevated metabolic gene signature supportive of increased glycolysis and glucose uptake to promote effector function. This outcome is coupled to an increased abundance of CD8+ T cell stem cell-like progenitors that maintain effector functions. Additionally, pharmacologic blockade of PSGL-1 curtails T cell exhaustion, indicating that PSGL-1 represents an immunotherapeutic target for PD-1-blockade-resistant tumors.
Developmentally distinct CD4+ T(reg) lineages shape the CD8+ T cell response to acute Listeria infection. Dolina JS, et al. PNAS, 2022. https://doi.org/10.1073/pnas.2113329119.
MicroRNA-139 expression is dispensable for the generation of influenza-specific CD8+ T cell responses. Hope JL, et al. Journal of Immunology, 2022. https://doi.org/10.4049/jimmunol.2000621.
Lessons in antiviral immunity. Hope JL, Bradley LM. Science, 2021. https://doi.org/10.1126/science.abf644.
FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells. Shen JZ, et al. Cell, 2021. https://doi.org/10.1016/j.cell.2020.11.042.
Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by Tcf7 promoter methylation. Zhao M, et al. PLoS Pathogens, 2020. https://doi.org/10.1371/journal.ppat.1008555.
Microenvironment-dependent gradient of CTL exhaustion in the AE17sOVA murine mesothelioma tumor model. Hope JL, et al. Frontiers in Immunology 2020. https://doi.org/10.3389/fimmu.2019.03074.
Striking a balance - cellular and molecular drivers of memory T cell development and responses to chronic stimulation. Hope JL, et al. Frontiers in Immunology, 2019. https://doi.org/10.3389/fimmu.2019.01595.
Long-term persistance of exhausted CD8 T cells in chronic infection is regulated by microRNA-155. Stelekati E, et al. Cell Reports, 2018. https://doi.org/10.1016/j.celrep.2018.04.038.
The transcription factor T-bet is regulated by microRNA-155 in murine anti-viral CD8+ T cells via SHIP-1. Hope JL, et al. Frontiers in Immunology, 2017. https://doi.org/10.3389/fimmu.2017.01696.
Public clonotypes and convergent recombination characterize the naïve CD8+ T-cell receptor repertoire of extremely preterm neonates. Carey AJ, et al. Frontiers in Immunology, 2017. https://doi.org/10.3389/fimmu.2017.01859.
Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis. Artlett CM, et al. Arthritis Research & Therapy, 2017. https://doi.org/10.1186/s13075-017-1331-z.
Rapid evolution of the CD8+ TCR repertoire in neonatal mice. Carey AJ, et al. Journal of Immunology, 2016. https://doi.org/10.4049/jimmunol.1502126.
Phosphatidylinositol 3-kinase p110(delta) isoform regulates CD8+ T cell responses during acute viral and intracellular bacterial infections. Gracias DT, et al. Journal of Immunology, 2016. https://doi.org/10.4049/jimmunol.1501890.
Acute exposure to ZnO nanoparticles induces autophagic immune cell death. Johnson BM, et al. Nanotoxicology, 2014. https://doi.org/10.3109/17435390.2014.974709.
Abasic phosphorothioate oligomers inhibit HIV-1 reverse transcription and block virus transmission across polarized ectocervial organ cultures. Fraietta JA, et al. Antimicrobial Agents and Chemotherapy, 2014. https://doi.org/10.1128/aac.02991-14.
Type I interferon upregulates Bak and contributes to T cell loss during human immunodeficiency virus (HIV) infection. Fraietta JA, et al. PLoS Pathogens, 2013. https://doi.org/10.1371/journal.ppat.1003658.
The microRNA-155 controls CD8+ T cell responses by regulating interferon signaling. Gracias DT, et al. Nature Immunology, 2013. https://doi.org/10.1038/ni.2576.
Active Funding
W. W. Smith Charitable Trust Biomedical Research Grant : January 2025 - December 2025
Mary Kay Ash Foundation Pilot Award : July 2024 - June 2026
Sidney Kimmel Cancer Center Pilot Award : June 2024 - May 2025
Melanoma Research Alliance - Young Investigators Award : June 2024 - May 2027
Comprehensive NeuroAIDS Center Pilot Award : April 2024 - March 2025
Completed Funding
American Cancer Society - Institutional Research Grant : November 2023 - October 2024