Shengmin Yan, Ph.D.
Assistant Professor
Education & Affiliations
Biography
My research focuses on the mechanisms of liver injury caused by liver diseases or hepatotoxicity. It includes basic and translational studies on alcohol-associated liver disease (ALD), environmental hepatotoxicity, and metabolic dysfunction-associated steatotic liver disease (MASLD). Currently, I am elucidating the mechanisms and roles of bile acid-mediated cell death in the progression of ALD, particularly alcohol-associated hepatitis (AH). Additionally, my research interests include: 1) the role of autophagy in liver pathophysiology; 2) the formation and physiological functions of protein condensates in liver diseases, such as Mallory-Denk bodies; and 3) the impact of the hepatic microenvironment on the progression of liver diseases.
Positions and Employment
2023-Present Assistant Professor, Tulane University School of Medicine, New Orleans, LA
2020-2023 Instructor, Tulane University School of Medicine, New Orleans, LA
Research
Honors and Awards
2023, Fred Sanfilippo Visiting Lectureship Program Award, The American Society for Investigative Pathology
2020, PISA 2020 Monga-Hans Junior Faculty Scholar Award, The American Society for Investigative Pathology
2020, Junior Investigator Research Award, Society of Chinese Bioscientists in America-Hepatology Division (SCBA-CALS)
2019, ASIP Experimental Pathologist-in-Training (EPIT) Award, The American Society for Investigative Pathology
2017, Travel award, Gordon Research Conference on Alcohol-Induced End Organ Diseases, Ventura, CA, United States
2015, Beijing outstanding graduates
2015, Outstanding graduates, University of Chinese Academy of Sciences
2015, Di Ao scholarship, University of Chinese Academy of Sciences
2014, Award of merit student, University of Chinese Academy of Sciences
Research Support
Active
NIAAA K01 (K01AA031305) 09/14/23-08/31/28
Role: PI Direct cost: $650,432
Alcohol-associated cholestatic liver injury and mechanisms
The major goal of this project is to study the mechanisms and roles of intrahepatic cholestasis in alcohol-associated liver disease.
AASLD Pinnacle Research Award (PNC23-183584) 07/01/23-06/30/26
Role: PI Direct cost: $300,000
Roles and mechanisms of cholestasis in alcohol-associated hepatitis
The major goal of this project is to study the roles and mechanisms of cholestasis in alcohol-associated hepatitis.
Tulane University COR Research Fellowship 06/01/2024-05/31/2025
Role: PI Direct cost: $5,000
Plasma membrane rupture in alcohol-associated liver injury
The major goal of this project is to obtain transgenic mice to study the roles and mechanisms of plasma membrane rupture in alcohol-associated liver injury.
The Carol Lavin Bernick Faculty Grant 07/01/2024-06/30/2025
Role: PI Direct cost: $9,000
ZBP1 and autophagy-related liver pathology
The major goal of this project is to study the role of ZBP1 in alcohol-associated hepatitis and autophagy-related liver pathology.
Completed
LA CaTS Pilot Grant Round 9 10/01/20-03/31/22
Role: PI Direct cost: $33,000
The role of BID in NAFLD-related metabolic changes of hepatic macrophages
The major goal of this project is to study the role of BID in diet-induced obesity and hepatic steatosis.
Role: Principal Investigator
Contributions
Contributions to Science
1. Gut-liver interactions in liver disease
Alteration of gut microbiota is associated with pathogenesis of several liver diseases, including ALD, NAFLD and cholestasis. Autophagy-related gene 5 (Atg5) is critical for autophagy. In liver specific Atg5-knockout (Atg5∆hep) mice, I found an impact of hepatic autophagy deficiency on gut microbiota and ileal FXR activity, which in turn plays a protective role in autophagy deficiency-induced liver injury and ductular reaction.
- Yan, S., B. Khambu, X. Chen, Z. Dong, G. Guo, and X.-M. Yin (2021). "Hepatic autophagy deficiency remodels gut microbiota for an adaptive protection via FGF15-FGFR4 signaling." Cell Mol Gastroenterol Hepatol 11(4): 973-997. PMCID: PMC7898036
- Khambu, B., T. Li, S. Yan, C. Yu, X. Chen, M. Goheen, Y. Li, J. Lin, O. W. Cummings, Y. A. Lee, S. Friedman, Z. Dong, G. S. Feng, S. Wu, and X.-M. Yin (2019). "Hepatic Autophagy Deficiency Compromises Farnesoid X Receptor Functionality and Causes Cholestatic Injury." Hepatology 69(5): 2196-2213. PMCID: PMC6461497
2. Autophagy in alcohol-associated liver disease
Autophagy is an evolutionarily conserved cellular degradation process critical to maintaining metabolic homeostasis in the liver. Studies that acutely modulate autophagy pharmacologically or a molecular knockdown of autophagy-related genes have found that autophagy can affect the severity of steatosis and injury in ALD. My postdoctoral work focused on the direct impact of genetic deficiency of autophagy on ethanol-induced liver injury. I found that, while the protective role of autophagy is still shown in models where autophagy is acutely modulated and/or ethanol is actually administered, the prolonged status of deficiency in autophagy complicates the response to ethanol treatment. The timing of autophagy dysfunction, the exact autophagy gene being affected, and the ethanol treatment regime all affect the complexity of the relationship between autophagy deficiency and ethanol-induced liver injury.
- Yan, S., J. Zhou, X. Chen, Z. Dong, and X.-M. Yin (2019). "Diverse Consequences in Liver Injury in Mice with Different Autophagy Functional Status Treated with Alcohol." Am J Pathol 189(9): 1744-1762. PMCID: PMC6723229
- Wang, L., J. Zhou, S. Yan, G. Lei, C. H. Lee, and X.-M. Yin (2017). "Ethanol-triggered Lipophagy Requires SQSTM1 in AML12 Hepatic Cells." Sci Rep 7(1): 12307. PMCID: PMC5614958
3. Mechanistic insights to diet-induced fatty liver
NAFLD is the most common cause of chronic liver disease in Western countries. It is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. We and others have found that the loss of BID in mice leads to obesity resistance and hepatic steatosis induced by a high-fat diet. I found that BID-deficiency causes metabolomic changes in the liver, and gut microbiota contributes to the resistance of Bid-knockout mice to diet-induced obesity and hepatic steatosis. Collaborative work in our lab identified a dynamic change of TFEB signaling and autophagy activity in the liver feeding.
- Yan, S.#, J. Zhou#, H. Zhang#, Z. Lin, B. Khambu, G. Liu, M. Ma, X. Chen, N. Chalasani, and X.-M. Yin (2022). “Promotion of Diet-induced Obesity and Metabolic Syndromes by BID is Associated with Gut Microbiota.” Hepatol Commun 6(12): 3349-3362 (# co-first authors) PMCID: PMC9701492
- Zhang, H.#, S. Yan#, B. Khambu, F. Ma, Y. Li, X. Chen, J. A. Martina, R. Puertollano, Y. Li, N. Chalasani, and X.-M. Yin (2018). "Dynamic MTORC1-TFEB feedback signaling regulates hepatic autophagy, steatosis and liver injury in long-term nutrient oversupply." Autophagy 14(10): 1779-1795. (# denotes equal contribution) PMCID: PMC6135624
4. Mechanistic insights to the hepatotoxicity of PFOA
Perfluoroalkyl acids (PFAAs) are widely used anthropogenic compounds. Perfluorooctanoic acid (PFOA), one of the most dominant PFAAs in the environment, induces hepatotoxicity. Activation of hepatic peroxisome proliferator-activated receptor (PPAR) -α is an important mechanism of PFOA-induced hepatotoxicity. However, evidence from Ppar-α-knockout mice suggested that PPAR-α is not the only contributor to the hepatotoxic effects of PFOA. By studying mice following PFOA exposure, I identified a potential role of sterol regulatory element-binding proteins (SREBPs) activation in livers following PFOA exposure. Moreover, I found that PFOA alters insulin signaling pathway and leads to dysfunction of glucose metabolism. Finally, my research indicates that endoplasmic reticulum stress (ER-stress) and autophagy impairment are associated with PFOA-induced hepatotoxicy, and 4-phenylbutyrate, an ER-stress inhibitor, can partially reverse the toxic effects of PFOA.
- Yan, S., J. Wang, and J. Dai (2015). "Activation of sterol regulatory element-binding proteins in mice exposed to perfluorooctanoic acid for 28 days." Arch Toxicol 89(9): 1569-1578. PMID: 25092180
- Yan, S.#, H. Zhang#, F. Zheng, N. Sheng, X. Guo, and J. Dai (2015). "Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice." Sci Rep 5: 11029. PMCID: PMC4464286
- Yan, S., H. Zhang, J. Wang, F. Zheng, and J. Dai (2015). "Perfluorooctanoic acid exposure induces endoplasmic reticulum stress in the liver and its effects are ameliorated by 4-phenylbutyrate." Free Radic Biol Med 87: 300-311. PMID: 26159507
- Yan, S., H. Zhang, X. Guo, J. Wang, and J. Dai (2017). "High perfluorooctanoic acid exposure induces autophagy blockage and disturbs intracellular vesicle fusion in the liver." Arch Toxicol 91(1): 247-258. PMID: 26879310
5. Biomarker identification of PFAAs toxicity by omics analysis
Levels of circulating microRNAs (miRNAs) can be altered in various diseases, which makes them excellent candidates for novel biomarkers. In PFOA-exposed mice, I found that levels of circulating miRNAs are altered. Collaborative work further discovered that levels of miRNAs profiles are altered in testes and livers following exposure to different PFAAs. Functions of these miRNAs were also found to be associated with PFAA-induced toxicity.
- Yan, S., J. Wang, W. Zhang, and J. Dai (2014). "Circulating microRNA profiles altered in mice after 28 days exposure to perfluorooctanoic acid." Toxicol Lett 224(1): 24-31. PMID: 24459700
- Wang, J., S. Yan, W. Zhang, H. Zhang, and J. Dai (2015). "Integrated proteomic and miRNA transcriptional analysis reveals the hepatotoxicity mechanism of PFNA exposure in mice." J Proteome Res 14(1): 330-341. PMID: 25181679
- Lu, Y., J. Wang, X. Guo, S. Yan, and J. Dai (2017). "Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes." Toxicol Appl Pharmacol 318: 41-48. PMID: 28126411
- Zhang, H., Y. Lu, B. Luo, S. Yan, X. Guo, and J. Dai (2014). "Proteomic analysis of mouse testis reveals perfluorooctanoic acid-induced reproductive dysfunction via direct disturbance of testicular steroidogenic machinery." J Proteome Res 13(7): 3370-3385. PMID: 24940614
Complete List of Published Work on PubMed (total > 30):