Timo Burster, PhD

Research

Functional responsibilities of cathepsin G (CatG) in immunity, including bivalent regulation of major histocompatibility complex class I (MHC) molecules, which underscore a novel role of CatG within the immune system. Special Interests: Immune evasion of tumor cells and pathogens, modulating of the proteolytic activity of CatG, functional properties of CatG in T cells, immunosenescence. 

Our model of how exogenous CatG modulates cell surface expression of MHC I.

CatG proteolytically cleaves the N-terminal end of the extracellular domain of protease-activated receptor 1 (PAR1). As a result, the tethered activation ligand flips to the extracellular loop 2 and recruits intracellular G protein, which is capable of downstream signal transduction.

However, cleavage of the extracellular part of PAR1 by CatG can also lead to receptor inactivation, so-called dis-arming; thereby the tethered ligand as well as three extracellular loops of PAR1 are digested and blocks G protein-mediated signaling. This can be further enhanced by the interaction of lactoferrin (LF) with CatG. LF increases the proteolytic activity of CatG and augments a CatG-mediated upregulation of MHC I molecules on the cell surface. The MHC I recycling pathway, for instance, is important for loading a new set of antigenic peptides (viral derived or tumor-associated) to MHC I molecules in order to be displayed on the cell surface for CD8+ T cell inspection. Distinct viruses or tumor cells prevent the synthesis of nascent MHC I molecules or interfere with the MHC I recycling pathway. The advantage of CatG-mediated upregulation of cell surface MHC I molecules is the efficacy to reuse MHC I within the MHC I recycling pathway, where MHC I molecules are pushed out to the cell surface instead of being degraded in the lysosome, as an additional model regarding how CatG circumvents immune evasion of viruses or tumor cells.

Lectures

Spring 2020:

BIOL 341 Biochemistry I and Recitation

BIOL 341 Biochemistry Laboratory

BIOL 410 Introduction to Immunology

Fall 2019:

BIOL 341 Biochemistry I and Recitation

BIOL 410 Introduction to Immunology

Spring 2019:

BIOL 341 Biochemistry I and Recitation

BIOL 341 Biochemistry Laboratory

BIOL 480 Molecular Immunology 

Fall 2018:

BIOL 410 Introduction to Immunology

BIOL 623 Advanced Immunology

Spring 2018:

BIOL 341 Biochemistry I and Recitation