Biology subjects

Jameson, M.

Publications and source records attributed to Jameson, M..

3 recordsLinked to original sources

bioRxiv2026

NR4A1 limits CD8⁺ T Cell effector responses and protection in tuberculosis

During Mycobacterium tuberculosis (Mtb) infection, CD8+ T cells exhibit dysfunction with impaired cytotoxicity and limited localization to granuloma cores. Using knockout mice, adoptive-transfer models and validation in macaque and human datasets, we identified the nuclear receptor NR4A1 as a key restrainer of CD8+ T cell immunity in tuberculosis (TB). Mtb-infected Nr4a1-/- mice displayed reduced bacterial burden, attenuated pathology, higher lung CD8+/CD4+ T cell ratios, and enhanced CD8+ T cell effector functions. Bulk and single-cell RNA sequencing revealed suppression of gene expression program linked with exhaustion, and expansion of Nkg7+ and Granzyme+ cytotoxic CD8+ T cell subsets in Nr4a1-/- mice. Spatial analyses demonstrated increased infiltration of Nkg7+ activated CD8+ T cells in Nr4a1-/- lesions. ChIP-qPCR showed NR4A1 binding to Nkg7 promoter, and Nkg7 knockdown abrogated the enhanced cytotoxicity of Nr4a1-/- CD8+ T cells. Pharmacologic inhibition of NR4A1 reduced Mtb burden and pathology, and restored Nkg7 expression and CD8+ T cell infiltration in the lung. Together, these findings identify NR4A1 as a negative regulator of CD8+ T cell-mediated immunity in TB and suggest the NR4A1-NKG7 axis as a novel host-directed therapeutic target. A one-sentence summary of your paperNR4A1 suppresses CD8+ T cell infiltration and cytotoxicity in TB lesions, and its inhibition enhances host resistance to Mtb infection.

immunology↗

bioRxiv2023

Minuteman - A versatile cloud computational platform for collaborative research

Secure platforms for bio-computation are critical to foster increasingly complex and data-intensive collaborations involving biomedical data. Here, we present Minuteman - an open-source cloud computing platform that can be securely used across organizations. Minuteman can be used for hosting data sources and running computational pipelines in an organized way. The platform consists of three fundamental features, 1) data operations including collaborative data processing and analytics, 2) customizable user access management for secure dissemination of the data, and 3) interactive exploration of the data through 3rd party (e.g. shiny, dashboard etc.) applications that can be scaled using docker containers. Strict data access rules and user-specific roles are applied across the whole platform to maintain data security. Minuteman is ideal for scenarios where data security, and privileged access are critical, such as industry-academia collaborations, and multi-institution consortiums. Using single-cell transcriptomics preprocessing, analyses and visualization pipelines across labs, we showcase the utility of the Minuteman platform for biomedical data analyses. Minuteman code is available at (https://github.com/hayatlab/minuteman)

bioinformatics↗

bioRxiv2022

The potentiative cytotoxic effect of IGF1R and EGFR inhibition on the Head and Neck Cancer Proteome

Head and neck cancers are the sixth most common cancer worldwide. Combinatorial targeted therapy has the potential to reduce drug resistance and increase cytotoxicity to head and neck squamous cell carcinoma (HNSCC). Using drug combinations is especially important when targeting the epidermal growth factor receptor (EGFR) since we previously demonstrated that activation of the insulin-like growth factor 1 receptor (IGF1R) is a mechanism for resistance against EGFR inhibition and that a combination of an IGF1R inhibitor, BMS754807, and an EGFR inhibitor, BMS599626, robustly inhibited the growth of HNSCC cell lines in vitro. To examine the mechanism of cytotoxicity, we performed protein pathway activation mapping via reverse phase protein array (RPPA) analysis of 145 proteins and phosphoproteins in five HNSCC cell lines to map key proteins and phosphoproteins important in tumorigenesis. By performing principal component analysis, calculating log fold changes, and constructing protein networks, we were able to provide evidence to support the hypothesis that the combination of IGF1R and EGFR inhibitors has a potentiative effect on inhibiting receptor tyrosine kinase signaling. The effects of the individual drugs are amplified, demonstrating that the combination more robustly inhibits the pathways of both receptors.

cancer biology↗