The immune system is highly complex and dynamic; thus understanding the interconnecting pathways that regulate immune responses is critical for the effective modulation and enhancement of immune protection by vaccination or immunotherapy. Historically, the majority of basic and translational research in immunology was limited to identifying and evaluating the function of individual immune components independent of their systemic context. The recent advent of high-throughput technologies has allowed us to start probing the complex interactions of immune cells both within and among diverse populations and tissue environments, providing high-dimensional data that captures system-wide states with molecular and cellular resolution. Large-scale biological data sets have the potential to significantly advance our understanding of the circuits driving immune organization, function, and dysregulation in disease. However, the volume and complexity of these data necessitate the development and use of advanced computational techniques to derive biologically meaningful conclusions, which often makes such approaches impenetrable to traditional cellular immunologists.
In my research, I combine systems approaches with experimental techniques to probe the interconnected pathways driving a variety of immune responses, and derive mathematically rigorous and clinically relevant insights into the spatial and temporal dependence of immune homeostasis.
At the Jill Roberts Institute for Research at Weill Cornell, I conducted studies focusing on understanding the role of immuno-regulatory factors in metabolic homeostasis and development of obesity. There, I continued to merge high-throughput sequencing and computational analysis with traditional cellular immunology to simultaneously track multidimensional metabolic and inflammatory states of adipose tissue lymphocytes throughout the development of obesity, providing novel insights into the mechanisms underlying the pathogenesis of inflammatory diseases associated with metabolic dysfunction.
Additionally, in continued collaboration with clinicians and basic researchers in the Tri-I community, I developed system-wide approaches to model cellular, transcriptional, and microbial changes in the context of obesity using clinically defined patient populations and organ donors. Recently, we were able to transcriptionally profile rare lymphocyte subsets from multiple tissues of previously healthy human organ donors, allowing us to distinguish fundamental differences between immunological states in mice and humans. I am currently working to extend this approach to incorporate cutting-edge computational techniques, including single-cell transcriptional profiling and splice variance analysis, which would offer the potential to systematically identify and monitor markers of disease progression tailored to individual patients, and help improve precision medicine to yield better diagnosis and treatment of multiple chronic inflammatory diseases.