Chronic obstructive pulmonary disease (COPD) has risen to the third leading cause of death in the US and specific and effective therapies are not available. Age is the most important risk factor for COPD. The mechanisms of age-related changes that lead to COPD pathogenesis are poorly understood. In this proposal, we will study whether Miz1 epigenetically represses NF-?B-dependent components of senescence-associated secretory phenotype (SASP), which acts in cooperation with inhibition of cell cycle arrest to suppress the senescence program, thereby preventing the development of COPD. Completion of this proposal, which includes animal and human studies, will provide fundamental insights into the pathogenesis of COPD and thus provide therapeutic targets.

Public Health Relevance

Chronic obstructive pulmonary disease (COPD) has risen to the third leading cause of death in the US and specific and effective therapies are not available. Age is the most important risk factor for COPD. The mechanisms of age-related changes that lead to COPD pathogenesis are poorly understood. Understanding the role of the transcription factor Miz1 in cellular senescence during the development of COPD should provide fundamental insights into our understanding of the pathogenesis of COPD and thus reveal novel therapeutic options.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL141459-02
Application #
9764468
Study Section
Lung Injury, Repair, and Remodeling Study Section (LIRR)
Program Officer
Postow, Lisa
Project Start
2018-08-19
Project End
2022-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611