ADP-ribosylation is a post-translational modification in which an ADP-ribose group from NAD+ is transferred to a substrate protein, releasing nicotinamide. This reaction is catalyzed by ADP-ribosyl transferases (ARTs), which are classified into mono-ADP-ribosyl transferases (mARTs) and poly-ADP-ribosyl transferases (pARTs), depending on the number of ADP-ribose units attached to the substrate. Poly-ADP-ribosyl transferases, such as PARP1, have been extensively studied in DNA repair and immune regulation, whereas mono-ADP-ribosyl transferases remain less understood. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP-ribose) polymerase (TiPARP, also known as PARP7) is a mono-ADP-ribosyl transferase known to influence multiple biological pathways, though its mechanism is still poorly characterized. Notably, PARP7 is expressed at low levels under normal conditions due to self-ADP-ribosylation but is upregulated in response to cellular stress. This unique regulatory feature highlights PARP7 as a critical and challenging target for investigating its role in cellular processes. In my graduate study, I found that PARP7 independently down-regulates the type I interferon signaling pathway. Mechanistically, PARP7 ADP-ribosylates STAT1 and STAT2, two transcription factors involved in the type I interferon signaling pathway, and promotes ubiquitination of the two proteins. Then PARP7 recruits p62, which has a ubiquitin-binding domain (UBA), and sends STAT1/STAT2 to degradation through autophagy. In the physiological settings, Knockout and inhibition of PARP7 will significantly relieve the multiple sclerosis symptoms in C57BL/6 mice. In my second project, I found that various kinds of bacteria can transcriptionally upregulate PARP7 mRNA and protein levels. Autoinducer precursor, 4,5-dihydroxy-2,3-pentanedione (DPD), released by bacteria, induces PARP7 mRNA. PARP7 ADP-ribosylates and recruits HUWE1 to ubiquitinate V.cholerae or V.cholerae-containing compartments. Ubiquitinated proteins are recognized by p62 and autophagosome and V.cholerae will be eventually degraded through autophagy. PARP7 WT bone-marrow-derived macrophages (BMDM) clear out bacteria better compared to KO BMDM. We also noticed that PARP7 KO C57BL/6 mice have a higher density of V.cholerae compared to WT C57BL/6 mice, consistent with the cellular results.