Translational Autoinflammatory Disease Section

Raphaela T. Goldbach-Mansky, M.D., M.H.S.
Acting Chief
Phone: 301-435-6243
E-mail: goldbacr@mail.nih.gov 

Translational Autoinflammatory Disease Section research focus is on applying a systematic approach to the clinical and immunological description of a number of autoinflammatory diseases. The lab uses targeted interventions to understand the role of specific inflammatory pathways in the pathogenesis of the autoinflammatory diseases. The discovery of single gene mutations, which modify the regulation of inflammatory pathways triggered by exogenous and endogenous “danger” molecules in a number of autoinflammatory diseases has provided new targets to treat and new concepts to understand this disease group. The studies on patients with neonatal-onset multisystem inflammatory disease, NOMID, have demonstrated the pivotal role of IL-1 beta oversecretion on the often devastating inflammatory multiorgan manifestations which include CNS and sensory organ inflammation (i.e. aseptic meningitis, cochlear inflammation and eye inflammation), rash, systemic inflammation with fevers and joint involvement. The overlap of clinical symptoms has led to the investigation of the role of IL-1 in other autoinflammatory/ autoimmune diseases.
 
Translational Autoinflammatory Disease Section works in partnership with Dr. Dan Kastner the Adjunct Investigator of NIAMS, and his laboratory group. This collaboration has led to the discovery and characterization of genes underlying a number of other autoinflammatory/autoimmune conditions.

Photo of Dr. Goldbach-Mansky, Dr. Liu, and Dr. Chen in the lab Photo of Damaris Garcia working in the lab

Selected Publications

Canna SW, de Jesus AA, Gouni S, Brooks SR, Marrero B, Liu Y, DiMattia MA, Zaal KJ, Sanchez GA, Kim H, Chapelle D, Plass N, Huang Y, Villarino AV, Biancotto A, Fleisher TA, Duncan JA, O'Shea JJ, Benseler S, Grom A, Deng Z, Laxer RM, Goldbach-Mansky R. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014 Oct;46(10):1140-6. doi: 10.1038/ng.3089. Epub 2014 Sep 14. PubMed Icon

Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Montealegre Sanchez GA, Tenbrock K, Wittkowski H, Jones OY, Kuehn HS, Lee CC, DiMattia MA, Cowen EW, Gonzalez B, Palmer I, DiGiovanna JJ, Biancotto A, Kim H, Tsai WL, Trier AM, Huang Y, Stone DL, Hill S, Kim HJ, St Hilaire C, Gurprasad S, Plass N, Chapelle D, Horkayne-Szakaly I, Foell D, Barysenka A, Candotti F, Holland SM, Hughes JD, Mehmet H, Issekutz AC, Raffeld M, McElwee J, Fontana JR, Minniti CP, Moir S, Kastner DL, Gadina M, Steven AC, Wingfield PT, Brooks SR, Rosenzweig SD, Fleisher TA, Deng Z, Boehm M, Paller AS, Goldbach-Mansky R. Activated STING in a Vascular and Pulmonary Syndrome. The New England Journal of Medicine 2014 Aug 7;371(6):507-18. doi: 10.1056/NEJMoa1312625. Epub 2014 Jul 16. PubMed Icon

Sibley CH, Chioato A, Felix S, Colin L, Chakraborty A, Plass N, Rodriguez-Smith J, Brewer C, King K, Zalewski C, Kim HJ, Bishop R, Abrams K, Stone D, Chapelle D, Kost B, Snyder C, Butman JA, Wesley R, Goldbach-Mansky R. A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease. Ann Rheum Dis. 2014 Jun 6. pii: annrheumdis-2013-204877. doi: 10.1136/annrheumdis-2013-204877. [Epub ahead of print] PubMed Icon

Sanchez GA, de Jesus AA, Goldbach-Mansky R. Monogenic autoinflammatory diseases: disorders of amplified danger sensing and cytokine dysregulation. Rheum Dis Clin North Am. 2013 Nov;39(4):701-34. doi: 10.1016/j.rdc.2013.08.001. Epub 2013 Sep 21. PubMed Icon

Almeida de Jesus A, Goldbach-Mansky R. Monogenic autoinflammatory diseases: Concept and clinical manifestations. Clin Immunol. 2013 Jun;147(3):155-74. doi: 10.1016/j.clim.2013.03.016. Epub 2013 Apr 9. PubMed Icon

Goldbach-Mansky R. Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1. Clin Exp Immunol. 2012 Mar;167(3):391-404. doi: 10.1111/j.1365-2249.2011.04533.x. PubMed Icon

Sibley CH, Plass N, Snow J, Wiggs E, Brewer C, King K, Zalewski C, Kim HJ, Bishop R, Hill S, Kicker P, Phillips Z, Dolan JG, Widemann B, Jayaprakash N, Pucino F, Stone D, Chapelle D, Snyder C, Butman JA, Wesley R, Goldbach-Mansky R. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease (NOMID) treated with anakinra. Arthritis Rheum. 2012 Jul;64(7):2375-86. doi: 10.1002/art.34409. PubMed Icon

Liu Y, Ramot Y, Torrelo A, Paller AS, Si N, Babay S, Kim PW, Sheikh A, Lee CC, Chen Y, Vera A, Zhang X, Goldbach-Mansky R, Zlotogorski A. Mutations in PSMB8 cause CANDLE syndrome with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. 2012 Mar;64(3):895-907. doi: 10.1002/art.33368. PubMed Icon

Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, Laxer R, Tedgard U, Edward CW, Pham TH, Booty M, Estes JD, Sandler NG, Plass N, Stone D, Turner ML, Hill S, Butman JA, Schneider R, Babyn P, El-Shanti HI, Pope E, Barron K, Bing X, Laurence A, Chapelle D, Clarke GI, Ohson K, Nicholson M, Gadina M, Yang B, Korman BD, Gregersen PK, van Hagen PM, Hak AE, Huizing M, Rahman P, Douek DC, Remmers EF, Kastner DL, Goldbach-Mansky R. Deficiency of the Interleukin-1 Receptor Antagonist (DIRA) A Systemic Autoinflammatory Disease of Skin and Bone.

Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, Kim HJ, Brewer C, Zalewski C, Wiggs E, Hill S, Turner ML, Karp BI, Aksentijevich I, Pucino F, Penzak SR, Haverkamp MH, Stein L, Adams BS, Moore TL, Fuhlbrigge RC, Shaham B, Jarvis JN, O'Neil K, Vehe RK, Beitz LO, Gardner G, Hannan WP, Warren RW, Horn W, Cole JL, Paul SM, Hawkins PN, Pham TH, Snyder C, Wesley RA, Hoffmann SC, Holland SM, Butman JA, Kastner DL. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. The New England Journal of Medicine 2006 Aug 10;355(6):581-92. PubMed Icon

See extended list of publications

 

Reviewed September 24, 2012