Research

Inflammatory Biology Section

Daniel Kastner, M.D., Ph.D.
Acting Chief, Inflammatory Biology Section
Phone: (301) 496-8364
Fax: (301) 402-0012
E-mail: kastnerd@mail.nih.gov

Research Overview

Since its inception as the Genetics Section of the Arthritis and Rheumatism Branch, the Inflammatory Biology Section of the Genetics and Genomics Branch has focused on understanding the molecular pathogenesis of inflammation. The general strategy of the Section has been to use genetic methods such as positional cloning to identify the genes underlying Mendelian disorders of inflammation, and then to employ the techniques of molecular and cell biology to delineate the role that these genes play in normal physiology and pathologic conditions. In 1997, the Section led an international consortium in the identification of the gene causing the recessively inherited disorder familial Mediterranean fever (FMF). The gene, denoted MEFV, encodes a novel protein called pyrin that is expressed primarily in leukocytes, appears to be involved in the regulation of cytokine processing and apoptosis, and is the prototype for a new family of proteins involved in the regulation of apoptosis and inflammation. In 1999, the Section discovered mutations in the p55 TNF receptor in patients with dominantly inherited periodic inflammation, and proposed the name TRAPS (TNF receptor associated periodic syndrome) to denote this condition. Most recently, the Section has collaborated with several other groups within and outside of the NIAMS to identify mutations in the pyrin gene family member CIAS1 in patients with the neonatal onset multisystem inflammatory disease (NOMID). Major projects of the section include: (1) further delineating the function of pyrin and related proteins, including biochemical analyses, studies of mice harboring various mutant forms of pyrin, and collaborative structural studies; (2) understanding the mechanisms by which TNF receptor mutations lead to disease, including studies of transfected wild-type and mutant receptor in cell lines, studies of knockin mice, and collaborative structural studies; (3) further delineating the mechanism by which CIAS1 mutations cause NOMID; and (4) identifying and characterizing mutations in additional genes that might lead to disorders of inflammation. In addition, in collaboration with Dr. Keith Hull in the Office of the Clinical Director, clinical studies including natural history protocols and therapeutic trials are ongoing.


 

Updated September 17, 2007