Vascular Immunobiology Mechanistic and Translational Studies

我们新发现的中性粒细胞过度活化、中性粒细胞胞外陷阱形成、病理性血栓形成前自身抗体的产生扰乱了急性COVID的内皮和先天免疫功能，这使我们研究了自身抗体和血栓炎症可能具有临床相关性的其他临床背景。我们确定了一种fda批准的药物，通过嘌呤能信号调节免疫和凝血系统，并将其转移到临床研究人员发起的随机临床试验中。为了阐明血栓炎性疾病的机制和潜在的治疗靶点，我们正在剖析细胞表型和分子信号网络，这些样本来自美国国立卫生研究院（nih）资助的三个随机COVID临床试验的患者。我们正在将研究结果与临床结果联系起来，为试验结果提供背景，这些分析对于为未来临床研究的诊断和治疗目标奠定基础非常重要。

Our nascent discovery of neutrophil hyperactivation, neutrophil extracellular trap formation, the production of pathologic prothrombotic autoantibodies that perturb endothelial and innate immune function in acute COVID have led us to examine additional clinical contexts where autoantibodies and thromboinflammation could have clinical relevance. We identified an FDA-approved drug that modulates the immune and coagulation systems through purinergic signaling, and moved this to the clinic in an investigator-initiated, randomized clinical trial. To elucidate mechanisms and potential therapeutic targets in thromboinflammatory disease, we are dissecting cellular phenotypes and molecular signaling networks using samples from patients enrolled in three, NIH-sponsored, randomized, COVID clinical trials. We are correlating findings with clinical outcomes to lend context to the trial results, and these analyses are important to lay the groundwork for diagnostic and therapeutic targets in future clinical studies.