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Immune Disorders & Inflammatory Diseases

Humans have evolved highly complex immune systems that are composed of specialized immune cells that protect the host from infection and damage. But an uncontrolled immune response such as chronic inflammation can itself inflict damage. And when the immune system is compromised by genetic mutation, individuals become more susceptible to diseases such as autoimmune disease.

Three groups also perform clinical work in affiliation with the Medical University of Vienna:

  • CeMM Adjunct Principal Investigator Kaan Boztug is studying the mutations underlying immuno deficiency disorders.
  • Former CeMM Principal Investigators Sylvia Knapp and Christoph Binder are working on the molecular mechanisms of innate immunity and inflammatory diseases.

Regulation of the inflammatory response

Inflammation is the first response of the innate immune system to infection or tissue damage and serves to recruit immune cells to the site of infection or tissue damage in order to eliminate pathogens and to repair damaged tissue. While our knowledge about acute inflammation is improving constantly, our understanding of the equally important process of resolution and tissue homeostasis is far less developed.

The innate immune system’s inflammatory response to invading pathogens is used to limit systemic spread of the infection and minimize tissue damage.

  • Sylvia Knapp’s group is studying molecular modulators of the inflammatory response with a focus on tissue resident macrophages and their role in tissue homeostasis and the resolution of inflammation.

Atherosclerosis & immunity

While acute inflammation is commonly beneficial, chronic or persistent inflammation can ultimately damage cells and tissues, and plays a causative role in several important human diseases, like atherosclerosis, which is the cause of heart attack and stroke.

Atherosclerosis is a chronic disease characterized by damage of vessel walls that is predominantly influenced by inflammation.

  • Christoph Binder’s group studies the role of the immune system in atherosclerosis and the molecular mechanisms at play. They investigate the role of oxidation-specific epitopes, which are thought to drive the inflammatory response and promote disease progression, and the role of natural antibodies, which confer protection against atherosclerosis and may be harnessed as a new therapeutic strategy for treating this common disease.

Intestinal immune homeostasis

The mammalian gut harbors trillions of bacteria that extensively modify diet and host-derived molecules, generating a number of biologically active substances with direct nutritional value and signaling capabilities. Although the overall impact of microbial colonization on the host has been characterized, the effects of dynamic changes in bacterial metabolism on intestinal physiology and mucosal immunity are currently unknown.

  • Clarissa Campbell's group at CeMM studies how feeding-induced changes in microbial metabolism dynamically regulate host physiology at the intestinal mucosa by using a curated list of bacterial molecules in a candidate-based approach, combined with unbiased, metabolomics-based profiling of bacterial metabolism in fed and fasted animals. By performing in vitro screens on immune cells and intestinal organoids, they aim at identifying host targets that integrate microbial-derived cues produced in distinct absorptive states

Genomics approaches for studying immunodeficiency disorders

Patients with so-called immunodeficiency disorders inherit genetic mutations that cause defective immune systems with a reduced infection-fighting capacity. These disorders are also linked with autoimmunity, but the underlying mechanisms that cause these phenotypes are generally unclear.

  • Kaan Boztug’s group analyses patients with immunodeficiency disorders using state-of-the-art genomic approaches available at CeMM including exome sequencing, in order to identify the underlying genetic mutations, and then go on to analyse their molecular functions.