The ability of T cells to dynamically adjust proteome composition is essential during stress. For that reason, protein turnover rates are optimized to balance energy-saving stability and dynamic flexibility serving as a rapid mechanism for activation or inhibition of signaling pathways when cells respond to environmental changes. The ability of a T cell to persist in harsh conditions is highly correlated with its ability to control tumor growth. While it is common to ask the question “how do T cells respond to stress?” the Koss lab intends to ask a fundamentally different question “how are T cells prepared for encountering stress?” The precise set of proteins T cells depended on to ensure adequate plasticity remains elusive. Dr. Koss is using an integrative multi-omic approach for the analysis of proteome turnover dynamics. This technique integrates proteome, transcriptome, and protein turnover profiling to determine the dynamic nature of protein expression. This technique allows us to understand the T cell proteome in a new dimension and will shed new light on overcoming the heterogenous solid tumor environment. 

NIH Reporter

Activated T cells and cancer cells are remarkably similar: proliferation, metabolic activity, and survival mechanisms. To shift the balance in favor of the immune response the Koss lab intends to utilize decades of research identifying cancer-evolved resistant mechanisms. This project aims to fight fire with fire and endow CAR-T cells with cancer-cell resistance mechanisms. 

Arkansas ranks 43rd in life expectancy, in part due to high cancer incidence, low preventive health screening, poor diet, and high environmental toxicant exposures (heavy metals, pesticides). Additionally, low population mobility results in prolonged environmental exposure and accelerated epigenetic age (DNA methylation informed), which correlate to diminished immune responses. How these factors impact the response to immune-based therapies for cancer has not been fully explored. The ability to predict a therapeutic benefit and the onset of immune-related adverse events (irAE) prior to treatment would undoubtedly extend lives. Dr. Koss and collaborators seek to leverage interdisciplinary expertise in epidemiology, aging, cancer biology, immunology, and bioinformatics to build the infrastructure required to study population immune signatures associated with immune checkpoint blockade (ICB) and Chimeric Antigen Receptor (CAR) T cell therapy response.