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Peter Andrija Nigrovic, MD
Associate Physician, Brigham and Women's Hospital
Associate Professor of Medicine, Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
Rheumatology, Immunology
75 Francis Street
Boston, MA 02115


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Research Narrative:
My laboratory studies basic mechanisms of inflammatory arthritis, in particular the pathways by which IgG antibodies trigger joint inflammation. Two groups within my lab work on related aspects of this biology:
 
1) Innate immune responders within the joint – mast cells, neutrophils and platelets. We found that synovial mast cells “jump start” arthritis by elaborating IL-1 production upon triggering via IgG and complement. The IL-1 family cytokine IL-33 promotes this effect both by priming mast cells to respond to immune complexes and by supporting mast cell survival in inflamed tissues. We found that the neutrophil surface protein Ly6G participates in a new mechanism regulating integrin-dependent migration, and that this mechanism can be targeted to block experimental arthritis. We are currently studying a potential human homolog. We helped identify platelet microparticles as a key inflammatory mediator in arthritis and continue to study the pro-inflammatory role of this lineage.
 
2) IgG Fc glycosylation as a modulator of antibody function. The function of IgG is modulated by variable sugars (glycans) that shape the protein structure of the IgG Fc and thereby modulate interaction with Fc receptors and complement. We study how these glycans change with age, gender, and disease, principally inflammatory arthritis. We are particularly interested in the role of IgG glycans in juvenile idiopathic arthritis (JIA) and as a regulator of humoral immunocompetence in children.
 
I am a medicine/pediatrics-trained rheumatologist with appointments at BWH and Boston Children’s Hospital, and direct the Center for Adults with Pediatric Rheumatic Illness (CAPRI) at BWH. I direct arthritis biorepositories at BWH and Children’s. I have an active interest in mentoring junior faculty, and started both a local Aims Review Committee to support grant writing and a nationwide inter-institutional mentoring program within pediatric rheumatology, termed AMIGO (the ACR/CARRA Mentoring Interest Group), that serves more than half of pediatric rheumatology fellows and junior faculty in the US and Canada

Education:
Harvard Medical School, 1995, MD

Resources:
Mast Cell Culture

Publications (Pulled from Harvard Catalyst Profiles):

1. Halyabar O, Chang MH, Schoettler ML, Schwartz MA, Baris EH, Benson LA, Biggs CM, Gorman M, Lehmann L, Lo MS, Nigrovic PA, Platt CD, Priebe GP, Rowe J, Sundel RP, Surana NK, Weinacht KG, Mann A, Yuen JC, Meleedy-Rey P, Starmer A, Banerjee T, Dedeoglu F, Degar BA, Hazen MM, Henderson LA. Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Pediatr Rheumatol Online J. 2019 Feb 14; 17(1):7.

2. Cunin P, Lee PY, Kim E, Schmider AB, Cloutier N, Pare A, Gunzer M, Soberman RJ, Lacroix S, Boilard E, Lefort CT, Nigrovic PA. Differential attenuation of ß2 integrin-dependent and -independent neutrophil migration by Ly6G ligation. Blood Adv. 2019 Feb 12; 3(3):256-267.

3. Beukelman T, Nigrovic PA. Juvenile Idiopathic Arthritis: An Idea Whose Time Has Gone? J Rheumatol. 2019 Feb; 46(2):124-126.

4. Cunin P, Nigrovic PA. Megakaryocytes as immune cells. J Leukoc Biol. 2019 Jan 15.

5. Grieshaber-Bouyer R, Nigrovic PA. Maestro endothelium conducts the neutrophils. Blood. 2018 Oct 25; 132(17):1734-1735.

6. Westra HJ, Martínez-Bonet M, Onengut-Gumuscu S, Lee A, Luo Y, Teslovich N, Worthington J, Martin J, Huizinga T, Klareskog L, Rantapaa-Dahlqvist S, Chen WM, Quinlan A, Todd JA, Eyre S, Nigrovic PA, Gregersen PK, Rich SS, Raychaudhuri S. Fine-mapping and functional studies highlight potential causal variants for rheumatoid arthritis and type 1 diabetes. Nat Genet. 2018 Oct; 50(10):1366-1374.

7. Li G, Martínez-Bonet M, Wu D, Yang Y, Cui J, Nguyen HN, Cunin P, Levescot A, Bai M, Westra HJ, Okada Y, Brenner MB, Raychaudhuri S, Hendrickson EA, Maas RL, Nigrovic PA. High-throughput identification of noncoding functional SNPs via type IIS enzyme restriction. Nat Genet. 2018 Aug; 50(8):1180-1188.

8. Vastert SJ, Nigrovic PA. Editorial: Toward Personalized Treatment for Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2018 Aug; 70(8):1172-1174.

9. Lee PY, Huang Y, Zhou Q, Schnappauf O, Hershfield MS, Li Y, Ganson NJ, Sampaio Moura N, Delmonte OM, Stone SS, Rivkin MJ, Pai SY, Lyons T, Sundel RP, Hsu VW, Notarangelo LD, Aksentijevich I, Nigrovic PA. Disrupted N-linked glycosylation as a disease mechanism in deficiency of ADA2. J Allergy Clin Immunol. 2018 Oct; 142(4):1363-1365.e8.

10. Dart AH, Michelson KA, Aronson PL, Garro AC, Lee TJ, Glerum KM, Nigrovic PA, Kocher MS, Bachur RG, Nigrovic LE. Hip Synovial Fluid Cell Counts in Children From a Lyme Disease Endemic Area. Pediatrics. 2018 05; 141(5).