Congratulations Dr. Greg Palmer (Radiation Oncology) and his colleagues for being awarded a NIH U01 grant titled “Mitigators of Radiation-Induced Endovascular Injury: Targeting Tie2 and Thrombocytopenia.” This is a Collaborative Research award, and incorporates imaging studies to be conducted in the laboratory of Dr. Greg Palmer of Medical Physics. Together with Co-PI’s Dr. Nelson Chao (Medicine) and Dr. Chris Kontos (Medicine and Cardiology), Dr. Palmer (Radiation Oncology) will investigate irradiative injury to the vascular endothelium and a promising therapeutic, AKB-9785. AKB-9785 is a VE-PTP inhibitor that acts on the Ang-1/Tie2 pathway. Tie2 regulates vascular integrity and maturation and maintains endothelial barrier function. Irradiation and other trauma downregulates Tie2, causing vascular leakiness, inflammation, and other pathological effects. Previous studies with AKB-9785 and other small molecule drugs have shown that by inhibiting VE-PTP, vascular barrier function can be normalized. Dr. Palmer’s role in this collaboration is to quantify and analyze in vivo vascular leakiness and changes in vascular morphology. In vivo optical imaging is used because it allows subcellular information to be gathered. The challenge with optical imaging is that skin and tissue heavily attenuate light in the visible spectrum. To overcome this problem, Dr. Palmer is developing a lung window chamber that will allow him to directly visualize, in high resolution, the microvasculature and fluorescent signal. Fluorescently-labeled dextran injected through the tail vein is a method for analyzing vascular leak. After irradiation, the gap between endothelial cells (i.e. the leakiness) increases, causing more dextran to accumulate in the extravascular tissue. Finally, the quantification of the extravascular dextran signal and the vessel morphology allows him to objectively compare the therapeutic effects of AKB-9785 on radiation-induced injury.
