Md Zahid Akhter, PhD

Blood vessels are lined by thin membrane called endothelial cells (ECs). When ECs do not work properly, it leads to uncontrolled transport of large number of molecules through the vessel walls. This causes lung disease, called acute lung injury (ALI), and its severe form of acute respiratory distress syndrome (ARDS), which is a life-threatening disease with no effective treatment. In ARDS, many ECs die. Our research has shown that the activity of a gene called DNA methyltransferase 3a (DNMT3) is increased in a mouse model of acute lung disease. Our research shows that when DNMT3a is missing, ECs can grow back better and the lung heals faster. This study will explore how this happens and whether blocking DNMT3a could lead to new treatments for patients with severe lung injury.

Update: This study examines how inflammation changes endothelial cells at the genetic level and whether those changes worsen acute lung injury, which can be life-threatening. We have focused on a protein called DNMT3a, which is involved in turning genes on and off without changing the DNA itself. Using specially engineered mice and advanced genetic tools, we found that severe inflammation caused by bacterial toxins increased DNMT3a activity and DNA methylation in lungs’ endothelial cells. These changes were linked to more inflammation, lung swelling and tissue damage. When DNMT3a was removed from endothelial cells or blocked with a drug, the mice had less lung injury and recovered more quickly. These findings suggest that DNMT3a plays a key role in the development of acute lung injury; therefore, therapies that block DNMT3a may help protect the lungs, reduce inflammation and improve recovery in people with acute lung injury.