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Lars Plate

Plate

Research

The focus of the group is to define the dynamics and the coordination of protein interaction networks in diverse cellular processes. Towards this goal, we develop new mass spectrometry-based proteomics and chemical biology tools. Dynamic protein-protein interactions govern many molecular, cellular, and organismal processes and altered interactions are intricately linked to disease states. For instance, in cancer disparate protein-protein interactions occur in signal transduction pathways, protein folding diseases arise from aberrant engagement of protein folding pathways, and pathogenic infections take advantage of host-pathogen protein interactions that co-opt cellular pathways. Our goal is to understand how protein interactions in the pertinent biological processes have to be properly timed and coordinated. Defining the pathological consequences of mistimed and uncoordinated protein interactions on disease states will then guide the identification of new therapeutic strategies.

The research in our group leverages multidisciplinary approaches at the interface of Chemistry and Biology, ranging from protein biochemistry and enzymology, to microbiology, and cell biology as far as proteomics and drug discovery.

Current research projects include:

Dynamics of chaperone interactions with client proteins during folding and secretion – Protein folding and assembly inside cells rely on the coordinated action of chaperones, co- chaperones and other quality control factors that comprise the proteostasis network. Our goal is to monitor the sequential engagement and interaction dynamics between client proteins and proteostasis network components during cellular protein folding. We are developing a mass spectrometry-based platform for time-resolved interactomics as well as new chemical probes and bioorthogonal protein labeling approaches.

 

Hemeprotein proteostasis and dysregulation by stress and disease – Our research identifies intracellular heme transport factors and heme chaperones, and defines how these interact and coordinate with the proteostasis network to facilitate timely insertion of heme during protein folding. Investigating how heme transport and and hemeprotein assembly is regulated during stress and disease will identify new targets to mitigate oxidative damage during cardiovascular disease or to intervene with malaria infections.

 

Coordination of host pathogen protein-protein interactions during flavivirus infections – Our research elucidates the timing and coordination of host pathogen protein interactions throughout the viral life cycle with a particular focus on uncovering novel dependencies on the host proteostasis pathways. These discoveries will point to new host processes as therapeutic targets to combat infection of several widespread viruses that pose global health threats, such as Dengue, Hepatitis C, or Zika Virus.