MuChun Tsai, MD

Flu damages cells in the airways and causes major lung damage and death. Cilia are hair-like structures that protrude out of airway cells and clear out debris. E3 ligases are proteins that may be involved in immune response. We found that the E3 ligase called MARCH10 is reduced in mice lungs after flu infection. High levels of MARCH10 were found in human lung cells with cilia, which decreased after a flu infection. When MARCH10 was depleted in lung cells, cilia movement decreased, which suggests that MARCH10 may play a role in ciliary function. When MARCH10 was overexpressed in the lung cells and infected with flu, a flu protein decreased. This suggests that MARCH10 may also alter flu infection. We will determine how flu decreases MARCH10 in lung cells. We will also determine what effect MARCH10 has on cilia function during flu infection. We will identify cilia proteins that bind to MARCH10 and determine if overexpressing or depleting these cilia proteins will alter cilia function or flu infection.

Update:

Our lab previously discovered that during influenza infection, the levels of MARCH10 mRNA, the genetic material that contains instructions that direct cells to make a protein, decreased in both mouse lung cells and human lung cells. Our research suggests that MARCH10 is regulated at the level of gene transcription (the process of making an RNA copy of a gene's DNA sequence). We also investigated the stage of influenza infection that is associated with a decrease in MARCH10 expression. We did not see a decrease in MARCH10 expression when human lung cells were exposed to inactivated influenza virus or when various types of immune molecules called interferons were used. This suggests a separate mechanism by which viral infection reduces MARCH10. Our next step is to evaluate whether specific viral proteins affect MARCH10 expression.