Monogenetic factors controlling autoimmunity and autoinflammation
Mendelian disease, primary immundoeficiency, autoinflammation, next generation sequencing, homozygosity mapping
Research interest of the Faculty Member
Dr. Boztug is interested in the molecular pathogenesis of autoimmune and autoinflammatory disorders. To pursue the goal of gaining a molecular understanding of the mechanisms which regulate immune homeostasis in health and disease, Dr. Boztug investigates patients with Mendelian forms of immunodeficiency and autoimmune/autoinflammatory disorders. In his laboratory at CeMM, he performs high-throughput genomic approaches including SNP-array based homozyosity mapping and deep sequening combined with a functional evaluation of the identified monogenetic defects by a broad range of technical approaches depending on the identity of the gene(s) identified.
Collaborating research groups where PhD Students could perform their research stay abroad
- Mirjam van der Burg, Erasmus Medical Center, Rotterdam
- Christoph Klein, Ludwig-Maximilians University, Munich
- Bodo Grimbacher, Centre for Chronic Immunodeficiency (CCI), Freiburg
Know-how and infrastructure of the research group
At Dr. Boztug’s previous institution at Hannover Medical School in Germany, he was able to identify the underlying genetic defect of a syndromic immunodeficiency disorder comprising congenital neutropenia and complex organ malformations, caused by deficiency of G6PC3. Lack of this enzyme leads to aberrant glucose metabolism which is linked to activation of the unfolded protein response and increase apoptosis (Boztug et al, NEJM 2009). In another sentinel work, he was one of the lead researchers in the recent discovery of the first Mendelian causes of inflamatory bowel diseases, caused by mutations in the Interleukin-10 receptor genes (Glocker EO*, Kotlarz D*, Boztug K*, et al NEJM 2009). This work has been critical in elucidating the key role for interleukin-10 for immune homeostasis in the gut.
Dr. Boztug has a dual appointment as Principal Investigator at CeMM and a Visiting Professor at the Department of Pediatrics and Adolescent Medicine of the Medical University Vienna since January 2011. His group currently consists of 5 people and has established a highly efficient workflow for rapid discovery of Mendelian disorders of the immune system involving homozyosity mapping and deep sequencing at his lab at CeMM. Through a large network of international collaboration partners enabling identification of novel genetic defects in informative families, Dr. Boztug and his team have already discovered several additional, novel monogenetic defects of the immune system. Ongoing studies are characterizing these defects in detail. One of the focuses of Dr. Boztug’s work and this CCHD subproposal is the eluciation of the molecular basis for autoimmunity and autoinflammation in human disease.