Tiangang Li
University of Oklahoma-Health Sciences Center, OK·Physiology
The liver controls blood sugar, fat and bile, and when that control fails, serious disease follows. These projects study two such failures.
- Fields
Physiology
Pharmacology
Medicine & Clinical Research
- Topics
nonalcoholic fatty liver disease
type 2 diabetes
insulin resistance
- Grants
- 2 known grants, through Apr 2030
What they work on
- Identify which Cullin-RING E3 ligase complex mediates the benefits of neddylation inhibitors on blood sugar and liver fat, using liver-specific knockout mice and AAV8 gene delivery in mouse models of fatty liver disease.
- Test whether blocking CRLs prevents the breakdown of insulin receptor substrate and reduces ChREBP-driven fat production in the liver. Measure effects with hyperinsulinemic-euglycemic clamps, transcriptomics and proteomics.
- Identify and validate CRL substrate receptors, the parts that choose which proteins get destroyed, as candidate drug targets for treating fatty liver disease and type 2 diabetes.
- Compare increasing doses of the man-made bile acid Gly-MCA with ursodeoxycholic acid for treating cholestasis in male and female Cyp2c70 knockout and Mdr2 knockout mice.
- Define how Gly-MCA is metabolized during its microbe-dependent liver–gut circulation, and how it changes bile acid composition, bile flow, intestinal absorption and gut barrier function.
- Test whether combining Gly-MCA with AAV-FGF15 or GalNac-siCYP7A1, which cut liver bile acid production, improves treatment of advanced cholestasis in mice.
More about the research
Fatty liver disease, closely tied to obesity and type 2 diabetes, has no effective drug therapy. Cholestasis is a condition in which bile backs up and its toxic acids injure the liver, and it has few treatment options. Both projects use mouse models to find new drug targets and test candidate treatments.
Why it matters
Fatty liver disease affects many people with obesity and type 2 diabetes, and no effective drugs exist. Cullin-RING E3 ligases could become new drug targets that lower both blood sugar and liver fat. For people with cholestatic diseases such as primary biliary cholangitis and primary sclerosing cholangitis, Gly-MCA could become a new liver-protecting treatment option. This could especially help patients who do not respond to or cannot tolerate current bile acid drugs.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jenessa Winston
Ohio State University, OH·Microbiology & Immunology·Early-career
Test whether daily supplementation with the secondary bile acid ursodeoxycholic acid (UDCA) changes susceptibility to and severity of Clostridioides difficile infection in IL10-knockout colitis mice.
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.
Nicholas Davidson
Washington University in St Louis, MO·Medicine & Clinical Research
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.
The school
University of Oklahoma-Health Sciences Center: 11 labs on PI Pages, $474M a year on research, 31 research doctorates a year.
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