Therapeutic Modulation of Host Defense Pathways

A finely tuned ensemble of host defense pathways, including the innate immune, complement, coagulation and contact systems, normally protect our bodies from blood loss and infection with microbial intruders. However, the intrinsic design of these systems to react instantly and almost indiscriminately to potential threats also renders them vulnerable to erroneous activation. Indeed, overwhelming stimuli during trauma or infection, cell/organ transplants organ biomaterial implants, but also age-related deposits and cellular debris are known to trigger unwanted host defense responses that can lead to clinical complications. Therapeutic modulation of host defense systems has there been recognized as a promising strategy for early therapeutic intervention in various immune, inflammatory and/or thrombotic disorders

Our group aims to develop novel therapeutic concepts to tame the excessive and/or misdirected activation of host defense pathways and evaluate them in clinically relevant models. Owing to the broad pathophysiological involvement of these pathways, the scope of potential indications is equally wide and encompasses thrombo-inflammatory and age-related diseases as well as transplantation medicine and biomaterial-induced complications. As starting points for our drug design strategies, we often take inspiration from microbial immune evasion strategies or from physiological regulators and modulators.

Ricklin D, Lambris JD. Preformed mediators of defense - Gatekeepers enter the spotlight. Immunological Reviews 274 (1), 2016, 5-8 (Pubmed).

Ricklin D, Reis ES, Lambris JD. Complement in disease: a defence system turning offensive. Nature Reviews: Nephrology 12 (7), 2016, 383-401 (Pubmed).

Inspired by Nature: Peptide-, Protein- and Carbohydrate-Based Therapeutics

Nature provides a fascinating and powerful system of basic building blocks (e.g., amino acids, monosaccharides) to generate a large and diverse variety of physiologically active agents ranging from hormones and cytokines to antimicrobial peptides and glycoproteins. Whereas the direct use of peptides, proteins and carbohydrates for therapeutic purposes has long been considered challenging, recent development in the design, production, formulation and administration of such compounds led to a resurgence of biopharmaceuticals. Starting from natural templates or screening efforts, and utilizing tools from biotechnology, protein engineering, computational and medicinal chemistry and structural biology, our group designs and refines peptide-, protein- and carbohydrate-based molecules with potential therapeutic value. The targeting of therapeutic entities to the ideal cellular or molecular target defines another important aspect of our research activities.