Acute chest syndrome (ACS) is a form of acute lung injury (ALI) and a leading cause of morbidity among SCD patients. SCD patients hospitalized with acute pain crises often develop ACS within the next few days, suggesting a role for vaso-occlusion in lung injury. However, the exact etiological mechanism that triggers ACS is still elusive and the available treatment is primarily supportive.

The Sundd lab aims to elucidate the molecular and biophysical mechanism of leukocyte-platelet-endothelium interaction during inflammation and how these events contribute to vaso-occlusive crisis (VOC) and ACS in SCD. To achieve this, we are using a multi-scale integrative physiologic approach, which involves in vivo multi-photon excitation (MPE) fluorescence microscopy in transgenic and knock-in mice, microfluidic assays with patient blood, total internal reflection fluorescence (TIRF) microscopy, structured illumination microscopy (SIM), laser confocal microscopy, electron microscopy and various biochemical approaches. 

This multi-scale approach enables us to address the link between the pathophysiology of ACS affecting the lung (macro-level response) to the aberrant cellular events (micro-level response) driving the vaso-occlusion, and the molecular interactions (nano-level response) that enable those cellular events. Identifying the molecular mechanism of vaso-occlusion in the lung will inspire therapeutics to prevent ACS in SCD patients.