The Luscinskas lab is interested in how circulating white blood cells, called leukocytes, are recruited to infected or injured organs and tissues. This process involves leukocyte migration across the vascular endothelial monolayer, which lines the entire vascular system. The emphasis is to understand the mechanisms underlying blood leukocyte adhesion and transmigration across the blood vessel wall during infection, injury or immune-specific responses. Since many patients receiving treatments for cancer have temporary loss of immune cell function and platelets and are at risk for infections or bleeding, it is important to understand how to facilitate improved immune cell surveillance in cancer patients.
Our laboratory developed an in vitro model to mimic small vessel blood flow characteristics, and combined it with live cell microscopy to observe leukocyte-endothelial cell adhesive interactions. We use viral vectors and CRISPR-Cas-9 technologies to add genes, delete (erase) genes, or to erase and replace genes that contain fluorescent tags in endothelial cells to study their dynamic behavior during leukocyte adhesion and transmigration with our microscopy system described above.
Ongoing projects include (1) the study of molecules that regulate leukocyte adhesion to endothelial cells or other surfaces. We focus on the molecule called CD47, also known as integrin associated protein. CD47 is necessary for integrins to adhere to surfaces. (2) CD47 plays a similar role to control integrin adhesion in endothelial cells, and CD47 also serves to integrate signals that coordinate passage of leukocytes. These projects rely on biophysical, cell biological and molecular biological approaches. (3) CD47 also regulates leukocytes that provide adoptive immunity, called T lymphocytes. Inhibition of CD47 can protect mice from models of neuroinflammation, and our lab is examining how this works in other mouse models.