Project 1:The goal of this proposal is to investigate the novel concept that oxidant-modified self-peptides produced by regulatory airway immune cells can trigger airway hyper-responsiveness(AHR). We have identified that myeloid-derived regulatory cells (MDRCs) regulate airway inflammation in mice and humans. MDRCs producing ROS modify self-proteins that are then recognized as neo-antigens. These neo-antigens stimulate autoantibody and T helper cell responses that cause or contribute to the immuno-pathology of asthma. This project combines basic and translational research with emphasis on studies with immune cells purified from airways and blood of mild to moderate asthmatics and healthy normal controls.

Project 2: The goal of this project is to develop strategies to target tryptophan metabolism pathways to enhance anti-tumor immunity for lung cancer. We are interested in understanding the mechanisms underlying metabolic reprogramming that occurs in tumor cells and immune cells of the tumor microenvironment (TME). We study the relationship between cellular energetics and amino acid metabolism in the TME. We use a syngeneic model of lung cancer and human samples from stage III and IV lung cancer patients to address these questions.

Project 3:The goal of this project is to study the role of exosomes in immune regulation in asthma. We are investigating whether airway exosomes from asthmatics mediate antigen-specific inflammatory responses that drive pathogenic T cell proliferation and polarization in asthmatics. These studies are conducted with human bronchoalveolar lavage samples and T cells isolated from airways and peripheral blood of mild to moderate asthmatics compared to healthy controls.


 
Project 4: The goal of this project is to investigate how differentiation and function of B cells are impaired during lung cancer progression. We will investigate the impact of myeloid-lineage cells on B cell responses and evaluate the role of amino acid metabolism in modulating B cell differentiation and function. We are particularly interested in understanding the role of regulatory B cell subsets in driving lung cancer progression. These studies will be carried out using a syngeneic model of lung cancer.