LSI Seminar Series: Wen-Xing Ding, Ph.D., University of Kansas Medical Center

Liver cells can adapt and protect themselves in response to stress by activating cellular protective mechanisms such as autophagy, which is a lysosomal degradation pathway that degrades cellular organelles and/or proteins as well as lipids inside the autolysosomes. To meet the needs of autophagic degradation, it is critical to maintain sufficient numbers of lysosomes to fuse with autophagosomes that form autolysosomes. Lysosomal biogenesis is regulated by the transcription factor EB (TFEB), which is a master transcription regulator of lysosomal biogenesis and autophagy.



Studies from our lab revealed that TFEB is impaired in alcoholic hepatitis and pancreatitis as well as in acetaminophen-induced liver injury. Overexpression of TFEB protects against alcohol and drug-induced tissue damage whereas deletion of TFEB exacerbates tissue damage. Studies from our lab also demonstrated that Nrf2, a transcription factor regulating antioxidant response, promotes liver injury and liver tumorigenesis in autophagy defective livers. More recently, our work suggests that both hyper- and hypo-activation of MTOR are detrimental to the liver resulting in the development of liver tumors. Together, our studies indicate that autophagy and lysosome play critical roles in maintaining liver homeostasis. Approaches to boost autophagy and TFEB pathways, which are often impaired in chronic liver diseases, may be promising for treating and preventing liver disease including alcoholic and non-alcoholic fatty liver diseases, drug-induced liver injury and liver tumorigenesis.