June 1, 2026 – Dr. Shi is selected to present orally his research project titled “Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction–associated steatohepatitis” at the 17^th CADA annual meeting to be held on June 2-5 in New Orleans, LA.

April 1, 2026 – Dr. Nuo Heng joins Shi lab as a postdoctoral fellow. He received his PhD degree at Nanjing Agricultural University in June of 2025.

October 1, 2025 - Dr. Yu Jin joins Shi lab as a postdoctoral fellow. Yu was trained as a postdoc at Harvard Medical School before joining us. He has expertise in cellular biology and bioinformatics.

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic fatty liver disease characterized by lipid accumulation (steatosis), inflammation, and liver fibrosis. MASH could develop to an advanced stage of liver disease, named cirrhosis, which is the leading cause of liver transplantation in developed countries. There is currently only one FAD-approved drug for the MASH treatment due to an incomplete understanding of the pathogenesis of MASH development. In addition, clinical studies have shown that MASH is an independent risk factor for cardiovascular disease (CVD), which is the leading cause of death worldwide.

The Dr. Shi lab is dedicated to uncovering the cellular and molecular mechanisms of MASH pathogenesis, currently focusing on the metabolism of liver macrophages, including liver resident Kupffer cells (KCs) and infiltrated bone marrow-derived macrophages (BMDMs), in clearing the different forms of dead hepatocytes (efferocytosis) during MASH progression and regression. The goal of our study is to discover new potential therapeutics for MASH treatment.

CURRENT PROJECT

Investigating the liver macrophage efferocytosis of dead hepatocyte in MASH

Hepatocyte death is a key feature of MASH, and released intracellular contents (such as ATP and mtDNA) activate hepatic stellate cells (HSCs), causing excessive extracellular matrix (ECM) production and liver fibrosis.  Macrophage efferocytosis of dead hepatocytes reduces intracellular contents from dead hepatocytes, causing less HSC activation. Meanwhile, efferocytotic macrophages reprogram to a pro-resolving phenotype, exhibiting anti-inflammatory / HSC activation through secreting pro-resolving factors and ECM degradation. This project aims to identify the secreted molecules from efferocytotic macrophages using multidisciplinary approaches, including proteomics, RNA sequences, and in vivo/ex vivo experiments. This project is currently funded by the R00 from NIH-NIDDK.

Selected Publications

1. Shi HX*, Wang X, Sloas C, Gerlach DB, Yurdagul A, Moore M, Jung EJ, Mirshahi F, Ronzoni L, Sanyal A, Valenti L, Lin CS, Montgomery J, Zinker B, Klichinsky M, Tabas I*. Impaired TIM4-mediated efferocytosis by liver macrophages contributes to liver fibrosis in metabolic dysfunction-associated steatohepatitis. Science Translational Medicine. 2025 Sep 10;17(815):eadv2106. [PubMed PMID: 40929246, PMCID: PMC12954589] *Corresponding authors

2. Wang X, Moore M, Shi HX, Xiao Y, Khalid S, Saleheen D, Kisseleva T, Stupack D, Lazar M, Tabas I. A Non-Apoptotic Caspase-8—Meteorin Pathway in Hepatocytes Promotes MASH Fibrosis. Nature Metabolism. 2025 Oct;7(10):2067-2082. [PMID: 41006904, PMCID: PMC12552128]

3. Moore M, Wang X, Kennelly JP, Shi HX, Ishino Y, Kano K, Aoki J, Cherubini A, Ronzoni L, Guo X, Chalasani NP, Khalid S, Saleheen D, Mitsche MA, Rotter JI, Yates KP, Valenti L, Kono M, Tontonoz P,Tabas I. Low MBOAT7 expression, a genetic risk for MASH, promotes a pro-fibrotic pathway involving hepatocyte TAZ upregulation. Hepatology. 2024 [PMID: 38776184, PMCID: PMC11822724]

4. Ghooray D, Xu M, Shi HX, McClain CJ, Song M. Hepatocyte-specific fads1 overexpression attenuates western diet-induced metabolic phenotypes in a rat model. International Journal of Molecular Sciences. 2024 [PMID: 38732052 PMCID: PMC11084797]

5. Shi HX*, Moore M, Wang X, Tabas I*. Efferocytosis in liver disease. JHEP Reports. 2023 [PMID: 38234410, PMCID: PMC10792655] (Review) *Corresponding authors

6. Wang X, Moore M, Shi HX, Miyata Y, Donnelly SK, Radiloff DR, Tabas I. Hepatocyte-targeted siTAZ therapy lowers liver fibrosis in NASH diet-fed chimeric mice with hepatocyte-humanized livers. Molecular Therapy-Methods & Clinical Development. 2023 [PMID: 38144682, PMCID: PMC10746533]

7. Schilperoort M, Ngai D, Sukka SR, Avrampou K, Shi HX, Tabas I. The role of efferocytosis‐fueled macrophage metabolism in the resolution of inflammation. Immunological Reviews. 2023 [PMID: 37158427, PMCID: PMC10615666] (Review)

8. Moore M, Wang X, Shi HX, Meroni M, Cherubini A, Ronzoni L, Parks E, Ibdah J, Rector RS, Valenti L, Dongiovanni P, Tabas I. Circulating Indian Hedgehog is a Marker of the Hepatocyte-TAZ Pathway in Experimental NASH and is Elevated in Humans with NASH. JHEP Reports. 2023, 100716 [PMID: 37035456, PMCID: PMC10074197]

9. Shi HX, Prough RA, McClain CJ, Song M. Different types of dietary fat and fructose interactions result in distinct metabolic phenotypes in male mice. Journal of Nutritional Biochemistry. 2023 Jan;111:109189 [PMID: 36272691]

10. Shi HX*, Wang X, Li F, Gerlach DB, Yurdagul A, Moore M, Zeldin S, Zhang H, Cai B, Zheng Z, Valenti L, Tabas I*. CD47-SIRPα axis blockade in NASH promotes necroptotic hepatocyte clearance by liver macrophages and decreases hepatic fibrosis. Science Translational Medicine. 2022; 14:eabp8309. [PMID: 36417485] *Corresponding authors

11. Mederacke I, Filliol A, Affo S, Nair A, Hernandez C, Sun Q, Hamberger F, Brundu F, Chen Y, Ravichandra A, Huebener P, Anke H, Shi HX, Martínez García de la Torre RA , Smith JR, Henderson NC , Vondran F, Rothlin CV, Baehre H, Tabas I, Sancho-Bru P, Schwabe RF. The purinergic P2Y14 receptor links hepatocyte death to hepatic stellate cell activation and fibrogenesis in the liver. Science Translational Medicine. 2022 Apr 6;14(639):eabe5795. [PMID: 35385339, PMCID: PMC9436006]

12. Wang X, Zeldin S, Shi HX, Zhu C, Saito Y, Corey KE, Remotti HE, Verna E, Pajvani UB, Schwabe RF, Tabas I. TAZ-Induced Cybb in Hepatocytes Contributes to Early Liver Tumorigenesis in Experimental Non-Alcoholic Steatohepatitis. Journal of Hepatology. 2021, Dec. 10 [PMID: 34902531 PMCID: PMC8934258]

13. Hardesty JE, Wahlang B, Prough RA, Head KZ, Wilkey D, Merchant ML, Shi HX, Jin J, Cave MC. Effect of Epidermal Growth Factor Treatment and Polychlorinated Biphenyl Exposure in a Dietary-Exposure Mouse Model of Steatohepatitis. Environ Health Perspect. 2021, 129(3):37010. [PMID: 33788613, PMCID: PMC8011667]

Complete List of Published Work in My Bibliography

Postdoctoral Fellows
The Shi lab for MASH disease is currently accepting post-doctoral researchers with a strong background in animal experience, cellular and molecular biology, immunology, and bioinformatic. Interested candidates should review the current research directions and contact Dr. Shi at hongxue.shi@lsuhs.edu for more details.

Graduate Students
The Shi lab for MASH disease has several research projects available for graduate students. Those who are interested should review the current lab research directions and contact Dr. Shi at hongxue.shi@lsuhs.edu for more details.

Contact the Shi Lab

LSU Health Shreveport
Department of Molecular and Cellular Physiology
Biomedical Research Institute, Room F4-26
1501 Kings Hwy
Shreveport, LA 71103

Hongxue Shi, PhD
Email: Hongxue.shi@lsuhs.edu
Lab: BRI F4-36/Medical School Building B-328/330
Office: BRI F4-26, Phone: 318-675-5128