Summary
This project investigates the mechanisms by which long-lived plasma cells (LLPCs) resist proteasome inhibitors (PIs) to develop better strategies for eliminating allospecific plasma cells that cause transplant rejection.
Proteasome Targeting for Alloreactive Plasma Cells
US · IL
NIH
grant
awarded
#nih-2R01AI154932-06
What they want
The research centers on the hypothesis that mature LLPCs are especially resistant to PI-induced cell death. Experiments will define how the proteasome interfaces with regulators within the endoplasmic reticulum (ER) such as the chaperone protein BiP and other cytosolic regulators of proteostasis including the autophagy regulator p62 and VCP/p97. Specifically, the project will define the role of BiP in controlling PI sensitivity in LLPCs, define key regulators of ER-to-cytosol protein trafficking/disposal and their role in controlling PI sensitivity in LLPCs, and identify the gene regulatory networks underlying LLPC resistance to PIs.
Deliverables
- Definition of the role of BiP in controlling PI sensitivity in LLPCs
- Definition of key regulators of ER-to-cytosol protein trafficking/disposal and their role in controlling PI sensitivity in LLPCs
- Identification of gene regulatory networks underlying LLPC resistance to PIs
Technical requirements
- Expertise in proteasome function and inhibitors
- Knowledge of endoplasmic reticulum (ER) and cytosolic regulators (e.g., BiP, p62, VCP/p97)
- Ability to study long-lived plasma cells (LLPCs)
- Research into gene regulatory networks
