Molecular and Clinical Immunology

Kaan Boztug, Molecular and Clinical Immunology

Inherited defects of the immune system (so-termed “inborn errors of immunity”, IEI, also known as primary immunodeficiencies) represent unique models to dissect essential nodes of the immune system. Many IEIs are characterized by autoinflammation or autoimmunity, which is the failure of the immune system to distinguish invading pathogens from self-resulting in inappropriate immune attacks on organs and tissues. Also, many common diseases are characterized by a multitude of autoimmune phenomena, however, the molecular mechanisms are often poorly understood.

Genomics approaches to study IEIs
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 developed based on these models, underlining the need to understand the pathophysiologic mechanisms specifically in humans.
We therefore study patients suffering from rare IEIs. In addition to the classical presentation with increased infections, many patients show features of sometimes severe autoimmunity or autoinflammation, and immune dysregulation, thus providing the unique opportunity to dissect some of those molecular mechanisms. We use genomics approaches like single nucleotide polymorphism (SNP) analysis and exome sequencing to pinpoint the underlying genetic mutations. We then delve into the molecular mechanisms using cultured cells and a variety of molecular biology assays. These investigations of specific diseases will ultimately also have an immediate impact on our understanding of the molecular architecture of the immune system in general.

Molecular genetics of childhood leukemias
We are also studying the genetics of malignant disorders of childhood. In conjunction with other groups at our partner institutions CeMM, MedUni Vienna and CCRI, we study patients with leukemias to identify the underlying genomic aberrations. We then combine these data with detailed drug-sensitivity testing to predict vulnerabilities of the leukemic cells for each patient as a proof of concept for future personalized treatment of pediatric cancer patients.