Ray Zuo, MD, Clinical Assistant Professor of Internal Medicine in the Division of Rheumatology, has been selected to receive the Rheumatology Research Foundation Investigator Award, with funding to being July 1, 2020. The Investigator Award is a Career Development Research Award, created by the Rheumatology Research Foundation, to encourage junior investigators in the period between completing post-doctoral fellowship training while being competitive for more significant funding and establishing themselves as independent investigators.
This award will fund Dr. Zuo's research to determine the extent to which anti-NET autoantibodies may be a new class of clinically-actionable biomarker that can inform personalized (and earlier) interventions among Antiphospholipid Syndrome (APS) patients.
Dr. Zuo's Research Project Summary
APS is a thromboinflammatory disorder that can have devastating effects on patients and their families. While it is well known from population studies that antiphospholipid antibodies (aPL) increase the risk of thrombosis; defining an individual patient’s susceptibility is hindered by an incomplete understanding of APS pathophysiology. In the clinic, there are no biomarkers utilized in day-to-day practice, beyond the aPL themselves.
A potential breakthrough in recent years is the implication of neutrophils and their pro-clotting remnants (known as neutrophil extracellular traps or NETs) in the pathogenesis of APS. Somewhat unexpectedly, our preliminary studies have also revealed evidence of anti-NET autoantibodies in patients with primary APS. These autoantibodies do not appear to correlate with traditional aPL. We speculate that this anti-NET activity may interfere with NET degradation and thereby predict certain APS clinical manifestations.
Our proposed research will leverage one of the largest APS biorepositories in the world and cutting-edge laboratory techniques (bioassays for NET degradation and thrombin generation, as well as a novel autoantigen microarray platform). These unique resources will be integrated to:
- Evaluate the prevalence, specificities, and clinical association of anti-NET autoantibodies in aPL-positive individuals
- Determine several potential aspects of autoantibody function
- Define the longitudinal relationship between aPL, NETs, and anti-NET autoantibodies as it relates to thrombin generation
The overarching goal of this research is to comprehensively define autoantibodies recognizing NET-associated antigens in aPL-positive individuals, and in doing so define both their clinical associations and pathogenic impact.