Autoimmune diseases like antiphospholipid syndrome (APS) and lupus occur when the immune system attacks the body’s own cells. One aspect of this autoimmunity is that APS/lupus patients develop “sticky” blood, making them highly susceptible to blood clots such as strokes (blood clots in the brain) and pulmonary emboli (blood clots in the lungs). Our laboratory studies why APS/lupus arises in certain individuals and what we can do reverse it.
In particular, our laboratory has discovered that a common type of white blood cell, known as the neutrophil, functions abnormally in APS/lupus. In healthy individuals, neutrophils protect the body by identifying and eradicating infections. In APS/lupus, neutrophils “go haywire” and release sticky, clot-provoking webs of DNA and proteins called neutrophil extracellular traps, or “NETs.”
Our laboratory is using cutting-edge technology to understand NETs from all angles, with active projects taking advantage of the latest advances in cell and molecular biology, pharmacology, genetics, and epigenetics.
When we are not seeing patients in the Rheumatology clinic, we are working as a multidisciplinary research group, which includes collaborators in Biomedical Engineering, Cardiovascular Medicine, and Vascular Surgery, to develop precision therapeutics that will neutralize NETs. Through this collaborative effort, our group is applying models and techniques that are entirely unique within the field of autoimmunity.
U-M Research Collaborators
- Paula Bockenstedt, MD
- Lola Eniola-Adefeso, PhD
- Ora Gewurz-Singer, MD
- Joan Greve, PhD
- Yogen Kanthi, MD
- Joe McCune, MD
- James Moon, PhD
- Mary O'Riordan, PhD
- Subramaniam Pennathur, MD
- David Pinsky, MD
- Andrew Vreede, MD
- Purinergic modulation of the autoimmune vascular phenotype (NIH-NHLBI)
- Neutrophil elastase as a therapeutic target in lupus (Lupus Research Alliance)
- Neutrophil adhesion and thrombosis in antiphospholipid syndrome (NIH-NIAMS)
- Role of neutrophil extracellular traps in diabetic cardiovascular disease (Michigan Diabetes Research Center)
- Defibrotide as a regulator of NETs and endothelial cells in antiphospholipid syndrome (Jazz Pharma)
- ER stress responses of lupus neutrophils (Burroughs Wellcome Fund)
- Clinical research of antiphospholipid syndrome (Burroughs Wellcome Fund)