Our computational-experimental hybrid laboratory uses big data to gain precise insights into the immune system, and leverages these insights to develop more effective immunotherapeutic strategies for cancer, immune-mediated diseases, and infections.
We particularly focus on understanding the complexity of cellular responses to cytokines in vivo. Cytokines, as fundamental elements of the immune system, play a pivotal role in health and disease. Cytokine-based therapies and cytokine antagonists have been used clinically to treat a wide range of conditions, including cancer, autoimmune and inflammatory disorders (e.g., arthritis), allergies, COVID-19, and hepatitis. Yet, the large number of cytokines and cell types and complex cellular responses to diverse cytokines have made it challenging to elucidate in vivo immune responses to cytokines, forming a major roadblock in immunology research.
To overcome this, we built the Immune Dictionary and its companion software Immune Response Enrichment Analysis (Cui et al, Nature, 2024), where we systematically characterized transcriptomic responses of all major immune cell types to each of >80 cytokines at single-cell resolution. This first global view of cellular responses to cytokines revealed that the complexity of cytokine responses and the plasticity of immune cells are far greater than previously understood. Our laboratory expands on this foundation through four areas of inquiry:
- Perturbational Single-Cell Genomics: We use large-scale perturbational single-cell genomics to explore biological processes modulated by cytokines, such as stem cell development and regeneration, as well as cellular responses of non-hematopoietic cells to cytokines, to understand the impact of the immune system on tissues and vice versa.
- Computational Method Development: We develop computational approaches to interpret immunogenomic data and create software for the scientific community to analyze cytokine responses, cellular polarization, and cell-cell communication networks in any diseases or therapies being studied.
- Functional and Mechanistic Studies: We perform functional studies on newly discovered cytokine-modulated immune cell states to uncover additional functions of cytokines or immune cells and the mechanisms of action. We then use cytokines to manipulate immune cells to enhance immunotherapeutic efficacy.
- Diseases and Therapies: We apply the cytokine framework to study diseases, aiming to better understand cytokine-mediated pathogenesis and develop more precise immunotherapeutic strategies for cancer, immune-mediated diseases, and infections.
We study immune responses in a variety of oral, craniofacial, and systemic diseases. The diseases or conditions we have studied (from animal models or human patients) include: oral cancer, melanoma, breast cancer, viral hepatitis (Cui et al, J Hepatol, 2024), Sjögren’s disease, inflammatory bowel disease, aging (Cui et al, J Immunol, 2021), juvenile idiopathic arthritis (Cui et al, Plos One, 2016), and periodontitis/peri-implantitis.
