We are working to understand whether increasing vascular integrity during immune complex mediated disease mitigatesinflammatory injury and end organ damage. Endothelial cells (ECs) line blood vessels, forming a barrier between circulatingblood and tissues. In the presence of inflammatory cytokines, endothelial cell barrier function is compromised and blood vesselsbecome leakier, allowing extravasation of circulating inflammatory mediators into tissues. Sphingosine 1- phosphate receptor 1(S1PR1) is highly expressed on ECs and regulates vascular permeability as well as leukocyte adhesion to ECs. We have shownthat targeting this receptor with small molecule agonists attenuates inflammatory injury in models of immune complex mediatedvasculopathy and that mice with an endothelial specific knock out (KO) of S1PR1 are more vulnerable to experimentalinflammatory arthritis. Moreover, mice with and EC specific gain of function of S1PR1 have delayed injury. We are also eager to understand the role of EC S1PR1 in lupus nephritis and whether augmenting EC S1PR1 will be protectivein this complex and debilitating disease. Our preliminary studies demonstrate that SLE kidney biopsies have decreased ECexpression of S1PR1 compared to healthy controls. Our understanding of how EC S1PR1 shapes the inflammatory and/orfibrotic response will be elucidated by ongoing studies using the EC S1PR1 KO and GOF mice in models of lupus nephritis. Our work thus far supports the hypothesis that endothelial S1PR1 should be targeted for the treatment of autoimmune rheumaticdisease. Animal models will help us determine whether S1PR1 agonists have additive or synergistic effects when combined withstandard immunosuppressive therapies. A potential advantage of this approach is that combined therapies might attenuateinflammation without increasing the risk of infection, a common sequela of current treatments.
Assistant Scientist; Assistant Attending, Hospital for Special Surgery
Assistant Professor, Weill Medical College of Cornell University
Assistant Professor, NewYork-Presbyterian Hospital
Mount Sinai School of Medicine
Rheumatology Fellow of the Year, 2002
English, Spanish, French
Binita Shaw, Nathalie Burg, Michael Pillinger, Chapter 11: Neutrophils, pg 161, Kelley & Firestein's Textbook of Rheumatology,2020.
Binita Shaw, Nathalie Burg, Michael Pillinger, Chapter 11: Neutrophils, pg 169, Kelley & Firestein's Textbook of Rheumatology,2017.
Nathalie Burg, Michael Pillinger, Steven Abramson: Chapter 14: Neutrophils and Eosinophils, pg 235. Kelley's Textbook ofRheumatology, Elsevier Saunders, 2005.
Michael Pillinger, Nathalie Burg, Steven Abramson: Chapter 14: Neutrophils and Small Molecule Mediators pg 160. RheumatoidArthritis, Lippincott, Williams & Wilkins, 2004.
Burg N, Salmon J, Hla T, Sphingosine 1-phosphate receptor-targeted therapeutics in rheumatic diseases, Nature Reviews Rheumatology, 2022, in press.
Burg N, Swendeman S, Worgall S, Hla T, and Salmon J, Sphingosine -1 Phosphate Receptor-1 signaling maintains endothelial cell barrier function and protects against immune complex-induced vascular injury, Vol. 70, No. 11, November 2018, 1879–1889.
Yanagida, K, Liu C, Faraco G, Galvani S, Burg N, Anrather J, Iadecola C, and Hla, T, Size selective opening of the blood-brain barrier by targeting endothelial sphingosine-1 phosphate receptor-1. PNAS 2017 Apr 25;114 (17):4531-4536.
Swendeman S, Cantalupo A, Xiong Y, Yuan H, Burg N, Hisano Y, Cartier A , Liu C, Blaho V , Zhang Y , Yanagida K, Galvani S1 , Obinata H , Salmon JE, Sanchez T , Di Lorenzo A, and Hla T Engineered S1P chaperone attenuates hypertension and ischemic injury, Science Signaling 2017 Aug 15;10(492).
Wang W, Burg N, Vootukuri S, Coller BS, Increased Smad2/3 phosphorylation in circulating leukocytes and platelet-leukocyte aggregates in a mouse model of aortic valve stenosis: Evidence of systemic activation of platelet-derived TGF-β1 and correlation with cardiac dysfunction, Blood Cells, Molecules, and Diseases, 2016 May;58:1-5.
Ahamed J, Burg N, Yoshinaga K, Janczak CA, Rifkin DB, Coller BS In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-beta1. . Blood 2008 Nov 1;112(9):3650-60.
Burg ND, Pillinger MH, The neutrophil: function and regulation in innate and humoral immunity.. Clinical Immunology 2001 Apr;99(1):7-17.
For more publications, please see the PubMed listing.
Poster Presentation, American College of Rheumatology 2021: Enhancing Endothelial Cell Barrier Function via Sphingosine -1 Phosphate Receptor 1 (S1PR1) - A Novel Treatment for Experimental Arthritis
Oral Presentation, American College of Rheumatology 2017: Sphingosine-1 Phosphate Receptor-1-Mediated Endothelial Cel lBarrier Function Protects Against Immune Complex-Induced Vascular Injury: A Potential Novel Therapeutic Target for SLE
Poster Presentation, The 14th International Workshop on Scleroderma Research 2015: Evidence of neutrophil activation andneutrophil extracellular traps in systemic sclerosis
Poster Presentation, American Society of Hematology 2004: Evidence supporting thiol-disulfide exchange as a novel mechanism of TGF-β-1 activation
Oral Presentation, Spring School in Systemic Autoimmune Diseases 2004: Platelet TGF-β1 Compartmentalization and Activation
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