We are interested in understanding the role of exosomes/extracellular vesicles in modulating the tumor microenvironment, facilitating metastasis, and mediating cellular cross talk. We use advanced tools of biochemistry, molecular biology, and synthetic biology to identify and interrogate the key players and mechanistic principles underlying intercellular communications. Ultimately, we hope to develop a total biological understanding of how exosomes function in the pathogenesis of cancer. We are also interested in the development of novel genome editing technologies to facilitate these experiments.
Our team utilizes the CRISPR-CAS9 system to edit the immune system to be able to engineer tumor associated macrophages to combat cancer. In this project we target the key elements of tumor associated macrophages, including HIF-1α, arginase 1, and the PD-L1-PD1 pathway to reverse the tumor suppressive phenotype of macrophages. The result of our work can be applicable to different tumors and activate an anti-tumor immune response.
Type 2 diabetes mellitus (T2DM) and periodontitis are chronic diseases affecting millions of people globally and have long been considered biologically linked. Although pro-oxidative, pro-inflammatory and catabolic effects have been described as mechanisms underlying the enhanced periodontal bone loss in diabetes, the upstream events involving innate immunity involvement and activation are still not fully understood. Our preliminary results indicate the activation of a subset of transcription factors that are dysregulated in both diabetes and periodontal disease. This activation polarizes macrophages to a hyperinflammatory phenotype. By understanding these mechanisms and key molecular drivers, we are looking to pinpoint targetable molecules to reverse this hyper inflammatory phenotype in periodontitis with and without diabetes.
Immune checkpoint blockade therapy has shown successful clinical outcomes in the treatment of various solid tumors such as head and neck squamous cell carcinoma (HNSCC), melanoma, non- small cell lung cancer (NSCLC) and others. However, immune checkpoint inhibitors work best in patients who exhibit certain tumor biomarkers. In a collaboration with the Department of Hematology Oncology, the Department of Systems Biology, and the Mailman School of Public Health at Columbia University we aim to identify biomarkers which are associated with treatment outcome in patients with solid tumors who underwent immunotherapy