Hong Ji, PhD

Particulate matter from air pollution has a significant negative impact on the airway and lung and contributes to many lung diseases. It induces a type of lung inflammation that is difficult to treat by currently available medicine in people with severe asthma and chronic obstructive pulmonary disease. Our research showed that Tet1, a protein that regulates how DNA is transcribed into RNA, can protect the lungs from this type of inflammation, and that targeting this protein may provide an opportunity to treat lung diseases induced and promoted by particulate matter. Studies from our group also suggest that this protective role of Tet1 may be due to the regulation of the pathway that fights against oxidative stress, a process that can potentially damage cells and is produced by particulate matter and other components of air pollution. We will investigate how Tet1 regulates the genes in this oxidative stress response pathway and test whether we can reduce lung inflammation by promoting Tet1 activity and regulate oxidative stress response.

Supported by the Mary Fuller Russell Fund

Update: We found that Tet1 regulates genes and pathways contributing to diesel exhaust particles (DEP)-induced inflammation by reducing oxidative stress. We also extended our findings from cell culture to samples from healthy subjects and COPD patients. Lastly, we explored several treatments designed based on our newly obtained understanding. Pilot studies showed that these treatments partially reduced particulate matter-induced lung inflammation. In the coming year, we will include more animals and treatment groups to confirm our preliminary observations showing that that targeting Tet1 and Tet1-regulated pathways reduces oxidative stress and alleviates DEP-induced lung inflammation. We expect the findings will reveal new targets suitable for interventions to reduce negative health effects of exposure to particulate matter from traffic and other sources.