Kaan Boztug

Inherited defects of the immune system—referred to as primary immunodeficiencies (PIDs)—represent powerful, naturally occurring models to investigate key components of human immune function. Many PIDs present with features of autoimmunity or autoinflammation. Autoimmunity arises when the immune system mistakenly attacks the body’s own cells and tissues, failing to distinguish them from invading pathogens. While a wide range of human diseases involve autoimmune responses, the molecular mechanisms behind them often remain poorly understood.

Our research group focuses on elucidating the molecular mechanisms that regulate immune homeostasis, autoimmunity, and immune dysregulation by studying model diseases such as primary immunodeficiencies and inflammatory bowel disease. We employ advanced genomic technologies, including whole-exome sequencing of patient samples, to identify disease-causing mutations. These efforts are complemented by functional assays to validate molecular findings. Our overarching goal is to deepen the molecular understanding of immune-related disorders and contribute to the development of personalized, precision medicine strategies.

Genomics Approaches for Studying Immunodeficiency Disorders

Although autoimmune diseases have been extensively studied in animal models, clinical observations underscore the limitations of these systems—only a subset of patients benefit from therapies derived from such models. This highlights the pressing need for detailed, human-focused research into the pathophysiology of immune disorders.

We study patients with inherited immune system disorders—primary immunodeficiency diseases—which often manifest not only with increased susceptibility to infections but also with severe immune dysregulation and autoimmunity. These patients offer unique insights into the molecular basis of immune dysfunction.

Using cutting-edge genomics approaches, such as single nucleotide polymorphism (SNP) analysis and exome sequencing, we identify the underlying genetic mutations responsible for disease. Follow-up studies include molecular and cellular assays using cultured cells to explore the implicated biological pathways. These investigations enhance our understanding of immune system architecture and support the development of precision diagnostics and therapies.

Molecular Genetics of Childhood Leukemias

Our research also extends to the study of childhood blood cancers, particularly the molecular genetics of pediatric leukemias. In collaboration with other research groups at CeMM, we analyze the genomes of patients with leukemia to detect specific genomic aberrations. These findings are integrated with comprehensive drug-sensitivity profiling to uncover individual vulnerabilities of leukemic cells. This work serves as a proof-of-concept for personalized cancer therapy, aiming to tailor treatment strategies based on each patient’s unique molecular profile.

 

Kaan Boztug joined CeMM as principal investigator in 2011. He studied medicine at the Universities of Dusseldorf, Freiburg (DE), and London (UK), followed by graduate training with Iain L. Campbell at the Scripps Research Institute, La Jolla (USA) and postgraduate research and clinical training with Christoph Klein at Hanover Medical School (DE). His laboratory combines next-generation sequencing and molecular biological techniques with system biology approaches to understand the genetics and molecular pathomechanisms of rare disorders of hematopoiesis and immunity. In 2019, Kaan Boztug took over the agendas of scientific director at St. Anna Children’s Cancer Research Institute (CCRI). He is director of CeRUD Vienna Center for Rare and Undiagnosed Diseases and the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD). He holds a dual appointment as professor of pediatrics and adolescent medicine at MedUni Vienna and as consultant in pediatric hematology and oncology and head of immunology at St. Anna Children’s Hospital. He received a Starting Grant of the European Research Council (ERC) in 2012 and an ERC Consolidator Grant in 2018. In 2019, Kaan Boztug was awarded the Johann Wilhelm Ritter von Mannagetta Prize for Medicine of the Austrian Academy of Sciences. In 2022, he was awarded a corresponding membership in the Austrian Academy of Sciences (ÖAW) in the Division of Mathematics and Natural Sciences.