CeMM Adjunct Principal Investigator

Kaan Boztug
Genetics of Malignant and Immune System Disorders

Assoc.-Prof. Dr. Kaan Boztug
Director, Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases
Director, CeRUD Vienna Center for Rare und Undiagnosed Diseases 

Adjunct PI, CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences
Associate Professor of Pediatrics and Adolescent Medicine, Medical University of Vienna
Consultant in Pediatric Hematology, Oncology and Immunology, St. Anna Children’s Hospital Vienna

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Inherited defects of the immune system (so-termed “primary immunodeficiencies”, PID) represent unique models to dissect essential components of the immune system in natura. A considerable number of PIDs are characterized by autoimmunity or autoinflammation. Autoimmunity is the failure of the immune system to distinguish between the body’s own cells and cells of invading pathogens, which results in an inappropriate immune attack on organs and tissues. Many human diseases are characterized by a multitude of autoimmune phenomena, however, the molecular mechanisms are often poorly understood.

Our group works on understanding some of the molecular processes that control immune homeostasis and autoimmunity using model diseases such as PIDs with immune dysregulation or inflammatory bowel disease. To do this, we utilize state-of-the art genomic approaches including exome sequencing of patient samples to identify causative genetic mutations, combined with a variety of functional assays. The ultimate aim of our research is to enhance the molecular understanding of these disorders to enable the use of tailored treatment approaches.

Genomics approaches for studying immunodeficiency disorders

Much effort has been spent on investigating autoimmunity in animal models. However our observations in the clinic show that only a fraction of patients respond to conventional therapies that are based on these models, underlining the need to understand the pathophysiologic mechanisms specifically in humans in better detail.

We study patients suffering from inherited defects of their immune systems, so-called primary immunodeficiency disorders. In addition to the classical presentation with increased infections, many patients show features of sometimes severe autoimmunity and immune dysregulation, thus providing the unique opportunity to dissect some of the molecular mechanisms in natura.

We use genomics approaches such as single nucleotide polymorphism (SNP) analysis and exome sequencing of patient samples to pinpoint the underlying genetic mutation. We then delve into the molecular mechanisms using cultured cells and a variety of molecular biology assays. These investigations will potentially have an immediate impact on our understanding of the molecular architecture of the immune system.

Molecular genetics of childhood leukemias

We are also studying the genetics of malignant disorders of childhood. In conjunction with other groups at CeMM, we study patients with leukemias to identify their underlying genomic aberrations. We then combine these data with detailed drug-sensitivity testing to predict vulnerabilities of the leukemic blasts for each patient as a proof-of-concept for future personalized treatment of cancer patients in the future.


Kaan Boztug studied Medicine in Düsseldorf, Freiburg and London, followed by his graduate training with Iain Campbell at the Scripps Research Institute (La Jolla, USA), and clinical training and postgraduate research with Christoph Klein at Hannover Medical School (Germany). He joined CeMM in 2011 and holds a dual appointment as Associate Professor at the Department of Paediatrics and Adolescent Medicine at the Medical University of Vienna. Since 2016, Kaan Boztug is director of the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases. He is also director of the recently established CeRUD Vienna Center for Rare and Undiagnosed Diseases and joint director of the Jeffrey Modell Foundation Center for Immunodeficiencies at the Medical University of Vienna and St. Anna Children’s Hospital.

In his work, Kaan Boztug has identified various novel primary immunodeficiencies, including neutrophil disorders such as G6PC3 and JAGN1 deficiency, IL10R and IL21 deficiency as Mendelian types of early-onset inflammatory bowel disease, and deficiencies of PRKCD, NIK and DOCK2 causing combined immunodeficiency syndromes.

Selected Papers

Google Scholar link: https://scholar.google.at/citations?user=d-AVNMAAAAAJ&hl=en

Dobbs K*, Zhang S-Y*, Domínguez Conde C*, Parolini S* et al (2015). Human DOCK2 mutations underlie a pleiotropic immunodeficiency. New Engl J Med, 372: 2409-22. (* shared first authorship) doi: 10.1056/NEJMoa1413462

Woutsas S et al (2015). Hypomorphic mutation in TTC7A causes combined immunodeficiency wild mild structural intestinal defects. Blood 125: 1674-1676. doi: 10.1182/blood-2014-08-595397

Serwas NK et al (2015). Atypical manifestation of LRBA deficiency with predominant IBD-like phenotype. Inflamm Bowel Dis 21: 40-7. doi: 10.1097/MIB.0000000000000266 Willmann KL*, Klaver S* et al (2014). Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity. Nature Commun 5: 5360. doi: 10.1038/ncomms6360

Ban SA et al (2014). Combined immunodeficiency evolving into predominant CD4+ lymphopenia caused by somatic chimerism in JAK3. J Clin Immunol 34: 941-53. doi: 10.1007/s10875-014-0088-2

Boztug K et al (2014). JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. Nature Genet 46: 1021-7. doi: 10.1038/ng.3069

Serwas NK et al (2014). Identification of ITK deficiency as a novel genetic cause of idiopathic CD4+ T cell lymphopenia. Blood 124: 655-657. doi: 10.1182/blood-2014-03-564930

Salzer E et al (2014). Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by loss-of-function mutation in IL21. J Allergy Clin Immunol 133: 1651-1659. doi: 10.1016/j.jaci.2014.02.034

Salzer E*, Santos-Valente E* et al (2013). B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ.. Blood 121: 3112-3116 (* shared first authorship) doi: 10.1182/blood-2012-10-460741

Santos-Valente et al (2013). A novel mutation in the complement component 3 gene in a patient with selective IgA deficiency. J Clin Immunol 33: 127-33 doi: 10.1007/s10875-012-9775-z

Boztug K et al (2009). A syndrome with congenital neutropenia and mutations in G6PC3. New Engl J Med 360: 32-43. doi: 10.1056/NEJMoa0805051

Glocker EO*, Kotlarz D*, Boztug K* et al (2009). Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. New Engl J Med 361: 2033-45. (* shared first authorship) doi: 10.1056/NEJMoa0907206