Inflammation has to be constantly restrained to avoid tissue or organ damage. Imbalanced production of proinflammatory cytokine production and interferons underlies a variety of diseases such as autoimmunity and cancer. Protein geranylgeranylation is a post-translational lipid modification that regulates a variety of cellular functions. Loss of protein geranylgeranylation leads to imbalanced cytokine production and inflammatory disease conditions such as that in the autoinflammatory mevalonate kinase deficiency in humans or in mice deficient for key enzymes catalyzing protein geranylgeranylation. We propose to use a mouse model in combination with biochemical approaches and human genetics to elucidate the mechanisms by which protein geranylgeranylation regulates inflammatory processes through maintenance of balanced cytokine production. Knowledge gained from the proposed research will not only benefit MKD patients, but also patients suffering from common inflammatory diseases such as arthritis and atherosclerosis.

Public Health Relevance

We propose to use mouse and human genetics in combination with biochemical approaches and proteomics to study how geranylgeranylation, a class of lipid modification of proteins, regulates innate immune response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI110695-03
Application #
9199063
Study Section
Innate Immunity and Inflammation Study Section (III)
Program Officer
Peyman, John A
Project Start
2014-12-01
Project End
2019-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705