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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. Nigrovic PA, Martínez-Bonet M, Thompson SD. Implications of juvenile idiopathic arthritis genetic risk variants for disease pathogenesis and classification. Curr Opin Rheumatol. 2019 Jun 04.

2. Fang C, Manes TD, Liu L, Liu K, Qin L, Li G, Tobiasova Z, Kirkiles-Smith NC, Patel M, Merola J, Fu W, Liu R, Xie C, Tietjen GT, Nigrovic PA, Tellides G, Pober JS, Jane-Wit D. ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-?B via phosphoinosotide remodeling of endosomes. Nat Commun. 2019 05 21; 10(1):2247.

3. Cunin P, Bouslama R, Machlus KR, Martínez-Bonet M, Lee PY, Wactor A, Nelson-Maney N, Morris A, Guo L, Weyrich A, Sola-Visner M, Boilard E, Italiano JE, Nigrovic PA. Megakaryocyte emperipolesis mediates membrane transfer from intracytoplasmic neutrophils to platelets. Elife. 2019 May 01; 8.

4. Ringold S, Angeles-Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, Colbert RA, Feldman BM, Ferguson PJ, Gewanter H, Guzman J, Horonjeff J, Nigrovic PA, Ombrello MJ, Passo MH, Stoll ML, Rabinovich CE, Schneider R, Halyabar O, Hays K, Shah AA, Sullivan N, Szymanski AM, Turgunbaev M, Turner A, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Rheumatol. 2019 Jun; 71(6):846-863.

5. Ringold S, Angeles-Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, Colbert RA, Feldman BM, Ferguson PJ, Gewanter H, Guzman J, Horonjeff J, Nigrovic PA, Ombrello MJ, Passo MH, Stoll ML, Rabinovich CE, Schneider R, Halyabar O, Hays K, Shah AA, Sullivan N, Szymanski AM, Turgunbaev M, Turner A, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res (Hoboken). 2019 Jun; 71(6):717-734.

6. Angeles-Han ST, Ringold S, Beukelman T, Lovell D, Cuello CA, Becker ML, Colbert RA, Feldman BM, Holland GN, Ferguson PJ, Gewanter H, Guzman J, Horonjeff J, Nigrovic PA, Ombrello MJ, Passo MH, Stoll ML, Rabinovich CE, Sen HN, Schneider R, Halyabar O, Hays K, Shah AA, Sullivan N, Szymanski AM, Turgunbaev M, Turner A, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis. Arthritis Care Res (Hoboken). 2019 Jun; 71(6):703-716.

7. Angeles-Han ST, Ringold S, Beukelman T, Lovell D, Cuello CA, Becker ML, Colbert RA, Feldman BM, Holland GN, Ferguson PJ, Gewanter H, Guzman J, Horonjeff J, Nigrovic PA, Ombrello MJ, Passo MH, Stoll ML, Rabinovich CE, Sen HN, Schneider R, Halyabar O, Hays K, Shah AA, Sullivan N, Szymanski AM, Turgunbaev M, Turner A, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis. Arthritis Rheumatol. 2019 Jun; 71(6):864-877.

8. Chang MH, Nigrovic PA. Antibody-dependent and -independent mechanisms of inflammatory arthritis. JCI Insight. 2019 Mar 07; 4(5).

9. Grieshaber-Bouyer R, Nigrovic PA. Neutrophil Heterogeneity as Therapeutic Opportunity in Immune-Mediated Disease. Front Immunol. 2019; 10:346.

10. 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.