Our lab addresses mechanistic and translational questions in human immunology using high-dimensional single-cell mass cytometry and ex-vivo cellular manipulation. Our goal is to enable a deeper understanding of normal immune function, and dysregulated immune processes in immunodeficiency, autoimmunity, and the overlap between the two.
The mechanistic focus is on understanding the immune molecular “checkpoints” that regulate pro-inflammatory versus anti-inflammatory signals. We leveraged high-dimensional single-cell mass cytometry (Cytometry Time Of Flight—TOF) and normal immune development to create templates of ‘normal’ human immune cellular behavior. Using these “reference maps” we can elucidate the roles of protein regulators and the dynamic relationships between innate and adaptive immune cell subsets, at the single-cell level. This work will enable a better understanding of how autoimmune and inflammatory disorders disrupt these regulated processes.
The translational focus is on understanding the basis of rare human diseases of the immune system. By uncovering the underlying mechanisms of immune disorders we can further our understanding of human immunology and develop improved diagnostics and therapeutic treatments. In particular, our lab is interested in 1) systemic inflammatory disorders such as systemic lupus erythematosus (SLE) and 2) primary immunodeficiency disorders that involve autoimmune/inflammatory complications such as common variable immunodeficiency (CVID), chronic granulomatous disease (CGD), STAT1 gain-of-function, STAT3 gain-of-function, PI3K deficiency, and others. Using patient samples, we harness the power of mass cytometry to identify specific cell subsets that are signaling and producing cytokines aberrantly. These findings, in conjunction with relevant clinical data, hold promising clinical translational applications—such as the identification of novel disease biomarkers with diagnostic and prognostic utility, as well as new therapeutic targets.
Click here for a list of Dr. Hsieh's recent publications.
