Nicholas Davidson
Washington University in St Louis, MO·Medicine & Clinical Research
Fatty liver disease is common, but only some patients go on to liver scarring (fibrosis) or liver cancer. This disease is called nonalcoholic fatty liver disease (NAFLD).
- Fields
Medicine & Clinical Research
Physiology
Biochemistry
- Topics
nonalcoholic fatty liver disease
nonalcoholic steatohepatitis
liver fibrosis
- Grants
- 3 known grants, through Jul 2030
What they work on
- Determine how the human TM6SF2 E167K variant alters fat loading onto APOB and the release of VLDL from the liver and chylomicrons from the gut, using liver-specific knockout and variant knock-in mice.
- Test how the Tm6sf2 variant influences the development of liver fibrosis and hepatocellular carcinoma in mice, and whether the same VLDL assembly defects occur in human HepG2 and iPS-derived liver-like cells.
- Examine how blocking fat-handling genes Fabp1 or Dgat2 in Mttp liver-knockout mice, which cannot export VLDL, respectively promotes or prevents liver cancer, and which signaling pathways drive the difference.
- Compare pathways found in these mouse models with gene-expression and metabolomic signatures from livers of patients with NASH-related liver cancer and impaired VLDL secretion.
- Support digestive disease research through a shared core center with imaging, organoid and gene-editing, and biobank and big-data cores, plus pilot grants for new investigators.
More about the research
Doctors cannot yet tell in advance which patients will progress, and there is no proven treatment. The research focuses on one route to disease: the liver's failure to export fat. The liver normally packages fat into very-low-density lipoproteins (VLDL), particles that carry fat into the blood. When this export fails, fat builds up in the liver. Alongside this research, Dr. Davidson helps lead a campus-wide digestive disease research center and its pilot grant program.
Why it matters
Most people with fatty liver disease never develop serious illness, but a subset progresses to scarring and liver cancer with no proven treatment. This work focuses on patients whose livers cannot export fat, including carriers of the common TM6SF2 E167K variant. It could help identify which patients are at risk and point to drug targets for reversing fibrosis and preventing liver cancer. The supporting research center aims to speed new therapies for patients with digestive diseases.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yong-Xu Wang
University of Massachusetts Chan Medical School, MA·Physiology
Test whether a newly identified adipokine, a hormone released by fat tissue, resolves NASH and associated metabolic problems in two different NASH mouse models.
Zhenyu Zhong
University of Texas Southwestern Medical Center, TX·Medicine & Clinical Research
Define how obesity-associated loss of nerve–immune communication in the liver contributes to hepatocellular carcinoma (HCC), using complementary mouse models and human liver specimens.
John Clarke
Washington State University, WA·Pharmacology
Define which protein phosphatase 2A-associated pathways mediate microcystin-LR effects on human HepaRG hepatocytes and LX2 stellate cells, the liver's scar-forming cells, co-cultured as 3D spheroids in static and microfluidic systems with pathway modulators.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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