Prithu Sundd Laboratory at Versiti Blood Research Institute
Sickle cell disease (SCD) is an autosomal recessive genetic disorder that affects more than 100,000 Americans and millions worldwide. Sickle cell anemia (SCA) is the most common form of SCD, which is caused by a substitution of hydrophobic valine (Val) for hydrophilic glutamic acid (Glu) at the sixth position in the beta globin chain. Under hypoxic conditions, the mutated hemoglobin (HbS) undergoes reversible polymerization to form long fibers, which cause red blood cells (RBCs) to sickle. It is believed that sickle RBCs (sRBCs) get trapped in small blood vessels, along with leukocytes and platelets, to cause vaso-occlusion, the predominant pathophysiology responsible for acute pain crises and emergency medical care among SCD patients.
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.
Prithu Sundd, PhD
Versiti Blood Research Institute
Adjunct Professor of Medicine (Hematology and Oncology)
Medical College of Wisconsin
Education and Training
Ohio University, Doctor of Philosophy
La Jolla Institute of Immunology, Postdoctoral Fellow