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Raphaela T. Goldbach-Mansky, M.D., M.H.S.

Investigator
Translational Autoinflammatory Disease Section
NIAMS
Building 10, Room 6D-47B
10 Center Drive
Bethesda, MD 20814
301-435-6243

Research Topics

Autoinflammatory diseases are a group of rare immune dysregulatory syndromes that present with unexplained fevers, rashes, joint pain, and inflammation in organs, including the central nervous system, the eyes, inner ears, bones, fat, blood vessels and muscles. Many of these symptoms present very early in life. The discovery of single gene mutations, which modify the regulation of inflammatory pathways that are triggered by exogenous and endogenous "danger" molecules, has provided new concepts to understand this disease group. It also continues to provide us with new targets for intervention.

Dr. Goldbach-Mansky's translational autoinflammatory research program focuses on clinical and translational studies in children with early onset autoinflammatory diseases. Her research team at the NIAMS conducts studies in patients with IL-1-mediated autoinflammatory diseases (including Neonatal Onset Multisystem Inflammatory Disease (NOMID) and Deficiency of the IL-1 Receptor Antagonist (DIRA) and in patients with IFN-mediated autoinflammatory diseases (including CANDLE, SAVI and other autoinflammatory interferonopathies).

The research team also evaluates and studies patients with as yet undifferentiated autoinflammatory diseases who are difficult to treat. Their conditions are often uncharacterized, but may be clinically similar to known autoinflammatory diseases.

The team applies a diagnostic approach that includes careful clinical evaluation, and genetics and immune evaluations to characterize the immune dysregulation with the ultimate goal of finding better treatments for these patients. Clues from the pathogenic and genetic studies in patients with NOMID pointed to dysregulation in an innate immune pathway that regulates the release of the proinflammatory cytokine, IL-1, and our clinical studies have led to the Food and Drug Administration's approval of the IL-1 blocking agent anakinra in the treatment of this condition. Other molecular defects identified in our patients have become the target for new drug development and these rare diseases have become the model to understand the pathogenesis of more common inflammatory diseases.

Biography

Dr. Raphaela Goldbach-Mansky received her medical degree from the University Witten-Herdecke, Germany, in 1990 and completed a combined residency in Internal Medicine and Pediatrics at Case Western Reserve University, Metro Health Medical Center. She completed her rheumatology fellowship training at NIAMS in 1999 and served as a Staff Clinician at NIAMS through 2008. Dr. Goldbach-Mansky is Acting Chief of the NIAMS Translational Autoinflammatory Disease Section. She leads the NIAMS autoinflammatory disease clinic and has built a translational research program focusing on clinical and translational studies in children with early onset autoinflammatory diseases. She co-founded the pediatric research clinic in NIAMS in 1999, and the Translational Autoinflammatory Research Initiative (TARI) to improve research in patients with rare autoinflammatory diseases.

Dr. Goldbach-Mansky's research focus is on applying a systematic approach to the clinical and immunological study of autoinflammatory diseases. Her group uses targeted interventions to understand the role of specific inflammatory pathways in the pathogenesis of autoinflammatory diseases.

Selected Publications

  1. 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. N Engl J Med. 2014;371(6):507-18.
  2. 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;46(10):1140-6.
  3. Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, Zalewski C, Kim HJ, Bishop R, Hill S, Paul SM, Kicker P, Phillips Z, Dolan JG, Widemann B, Jayaprakash N, Pucino F, Stone DL, 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 treated with anakinra: a cohort study to determine three- and five-year outcomes. Arthritis Rheum. 2012;64(7):2375-86.
  4. 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 proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. 2012;64(3):895-907.
This page was last updated on February 9th, 2015