Chemical signaling pathways have been extensively studied in immune cells. Despite the fact that these cells also experience physical forces, how mechanical forces influence immune cells at the molecular level is largely unknown. Additionally, the impact of immune cell mechanotransduction at the organismal level in physiological settings or in response to disease states remains elusive. We are establishing in vitro and in vivo models to answer these questions.

Rare mutations in PIEZO1 mechanically activated ion channels cause hereditary xerocytosis, a disorder characterized by red blood cell dehydration. Recently, comprehensive medical exams of xerocytosis patients identified other perplexing syndromes associated with PIEZO1 variants. We hypothesize that PIEZO1-dependent mechanotransduction could play important roles in various blood cell lineages beyond its normal functions in erythrocytes. We use humanized mouse models to uncover the molecular basis of these disorders.

Rapid developments in precision medicine and computational science have provided us with a growing number of genome and metabolome databases to explore. Our lab is using these data to explore uncharted territories of human biology by creating exciting hypotheses to test. We have already found new mutations in genes encoding mechanosensitive proteins associated with surprising phenotypic traits from half a million individuals. We will investigate more novel areas of human biology where mechanotransduction plays unrecognized roles.