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The Sauer Lab

Research

Mechanisms of Antigen Receptor Signaling in Lymphocyte Development and Function

T and B lymphocytes are key components of our adaptive immune system. They recognize pathogen derived antigens through surface bound T or B cell antigen receptors (TCR, BCR). Engagement of the TCR or BCR results in the activation of intracellular signaling cascades which are still ill understood, but critical to initiate and direct T and B cell development and function.

Because T and B cells defend us against infectious pathogens, impaired TCR or BCR signaling can result in severe immunodeficiencies. Another T cell function is to help protect us against cancer by killing tumor cells. Thus, defective TCR signaling can also contribute to cancer. Unfortunately, the beneficial functions of T and B cells come at a price. Misdirected antigen receptor signaling can lead to the emergence of T or B cells which react against innocuous antigens, such as environmental antigens like pollen, or autoantigens derived from our body's own constituent proteins. Misdirected lymphocyte reactivity against environmental antigens can result in allergies such as rhinitis or asthma, whereas misdirected T or B cell reactivity against autoantigens can result in autoimmune diseases such as rheumatoid arthritis or autoimmune diabetes.

Our core interests are the mechanisms by which antigen receptor signaling directs T or B cell development and function. Through the identification of novel genes involved in TCR or BCR signaling and detailed functional analyses of their encoded proteins, we hope to improve our understanding of the molecular mechanisms regulating T and B cell development, function - and malfunction. An understanding of the key molecular components involved in these processes will foster our understanding of the function of the adaptive immune system and advance our knowledge in the fields of Immunology and Signal Transduction in general.

In addition, our studies will help to identify and validate novel targets for pharmacological modulation of the adaptive immune system in disease. Thus, we also hope to ultimately contribute to the discovery and development of novel drugs which provide new and improved therapies for immune disorders ranging from immunodeficiencies to allergies to autoimmune disorders and cancer.

To achieve these goals, we are currently pursuing the following main projects:

  1. Using Functional Genomics to Identify Novel Genes Involved in Lymphocyte Development and Function
  2. Inositol-Polyphosphate Signaling in Lymphocyte Development and Function
  3. Multidisciplinary Analyses of Kinase Function and Small Molecule Inhibition