Dr Dan Kastner - Public Lecture Award 2016

Prof Ed Lavelle, President of ISI presented the ISI Public Lecture Award 2016 to Dr Dan Kastner (NIH, Bethesda, USA) on 23rd March.

Dr Kastner Public Lecture: “Old Dogs, New Tricks: Autoinflammatory Disease Unleashed”

The 2016 recipient of the ISI Public Lecture Award was Dr. Dan Kastner (National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA). Dr. Kastner presented his public lecture, in association with The Irish Times, on Wednesday, 23rd March 2016 entitled, “Old Dogs, New Tricks: Autoinflammatory Disease Unleashed” in the Tercentenary Hall, Trinity Biomedical Sciences Institute (TBSI), TCD.

This lecture also marked part of the ISI’s contribution to the EFIS’s “European Day of Immunology.”

Biography:

Dan Kastner, M.D., Ph.D.

Scientific Director, Division of Intramural Research NIH Distinguished Investigator, Head, Inflammatory Disease Section

Dr. Dan Kastner obtained his A.B. summa cum laude in philosophy from Princeton University and a Ph.D. and M.D. from Baylor College of Medicine. After completing an Internal Medicine residency and chief residency also at Baylor, Dr. Kastner moved to the NIH in 1985. He completed clinical Rheumatology training in the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and then rose through the NIAMS faculty ranks to become NIAMS Clinical Director from 2005 to 2010. From 2008 to 2011 he was also the first NIH Deputy Director for Intramural Clinical Research. Since late 2010 he has served as Scientific Director of the Division of Intramural Research of the National Human Genome Research Institute (NHGRI). Throughout his career at the NIH Dr. Kastner’s research has focused on using genetic and genomic strategies to understand inherited disorders of inflammation, often stimulated by patients seen at the NIH Clinical Center. Dr. Kastner’s laboratory identified the gene mutated in familial Mediterranean fever by positional cloning, discovered the genetic basis for a second recurrent fever syndrome they named TRAPS (TNF receptor-associated periodic syndrome), and made seminal genetic discoveries that establish other distinct illnesses as disorders of the IL-1 pathway, thus helping to define the role of IL-1 in human biology and establishing the conceptual basis for therapeutic trials with IL-1 inhibitors. More recently his laboratory has utilized genomic approaches in genetically complex disorders, such as Behçet’s disease, and Dr. Kastner continues to maintain a very active clinical research program. His group also proposed the now widely accepted concept of autoinflammatory disease to denote disorders of innate immunity. Dr. Kastner has won a number of awards and honors, including election to the National Academy of Sciences in 2010 and to the Institute of Medicine of the National Academies in 2012.

General Summary

The Inflammatory Disease Section (IDS) studies the genetics, pathophysiology and treatment of inherited disorders of inflammation through an integrated clinical and laboratory research program. The group has investigated single-gene and genetically complex inflammatory disorders for almost twenty-five years, and proposed the now widely accepted concept of autoinflammatory disease for a class of disorders of innate immunity.

Many of the section’s most important projects began with patient encounters in the NIH Clinical Center. This includes the identification of the gene mutated in familial Mediterranean fever (FMF); the discovery of the tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS); the recognition of multiple disorders of interleukin 1 signaling; and the very recent description of the deficiency of adenosine deaminase 2 (DADA2), a disorder that can present with recurrent fevers, rash, childhood strokes and inflammation of the blood vessels.

The section continues to maintain a vigorous clinical research program, following a cohort of over 1,700 patients with autoinflammatory disease, and laboratory efforts currently focus in three major areas. First, the IDS uses next-generation genome sequencing technology to decipher cases in which mutations in a single gene lead to disease. Second, the group is utilizing dense maps of genetic markers spanning the human genome and genome sequencing strategies to understand the basis of genetically complex disorders such as Behçet’s disease, which can cause severe oral, genital, and ocular inflammation, and scleroderma, in which there is thickening of the skin and at times scarring of the internal organs. Third, the IDS uses tissue culture, biochemistry, and animal models to understand the precise mechanisms of inherited inflammatory disease. In this way, the Section develops the conceptual underpinnings for new therapeutic trials, some of which are conducted at the NIH Clinical Center.

Selected Publications

1. Remmers EF, Cosan F, Kirino Y, Ombrello MJ, Abaci N, Satorius C, Le JM, Yang B, Korman BD, Cakiris A, Aglar O, Emrence Z, Azakli H, Ustek D, Tugal-Tutkun I, Akman-Demir G, Chen W, Amos CI, Dizon MB, Kose AA, Azizlerli G, Erer B, Brand OJ, Kaklamani VG, Kaklamanis P, Ben-Chetrit E, Stanford M, Fortune F, Ghabra M, Ollier WE, Cho YH, Bang D, O’Shea J, Wallace GR, Gadina M, Kastner DL, Gül A. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet’s disease. Nat Genet. 2010;42(8):698-702.

2. Simon A, Park H, Maddipati R, Lobito AA, Bulua AC, Jackson AJ, Chae JJ, Ettinger R, de Koning HD, Cruz AC, Kastner DL, Komarow H, Siegel RM. Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndrome. Proc Natl Acad Sci U S A. 2010;107(21):9801-6.

3. Kastner DL, Aksentijevich I, Goldbach-Mansky R. Autoinflammatory disease reloaded: a clinical perspective.Cell. 2010;140(6):784-90.

4. Brydges SD, Mueller JL, McGeough MD, Pena CA, Misaghi A, Gandhi C, Putnam CD, Boyle DL, Firestein GS, Horner AA, Soroosh P, Watford WT, O’Shea JJ, Kastner DL, Hoffman HM. Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity. Immunity. 2009;30(6):875-87.

5. Booty MG, Chae JJ, Masters SL, Remmers EF, Barham B, Le JM, Barron KS, Holland SM, Kastner DL, Aksentijevich I. Familial Mediterranean fever with a single MEFV mutation: where is the second hit? Arthritis Rheum. 2009;60(6):1851-61.