Hang Shi
Georgia State University, GA·Physiology
Eating more energy than the body burns over a long time leads to obesity and to related diseases such as fatty liver disease. Diet and temperature are part of that picture, but they do not change our genes.
- Fields
Physiology
Biochemistry
Genetics
- Topics
obesity
brown adipose tissue
beige adipocytes
- Grants
- 2 known grants, through Jun 2031
What they work on
- Test whether deleting or overexpressing Uhmk1, a gene that supports nerve-fiber growth, in mouse sympathetic neurons changes nerve supply to fat, brown/beige fat heat production and energy expenditure during cold exposure.
- Determine whether loss of Uhmk1 in sympathetic neurons worsens, and its overexpression prevents, obesity caused by a high-fat diet in mice. Identify the molecular pathways through which Uhmk1 drives cold-induced nerve growth into fat.
- Test whether changing DNA methylation, the chemical marking set by the enzyme DNMT3A, at the Uhmk1 control region alters sympathetic nerve supply to fat, heat production and energy metabolism.
- Use mice with liver-specific deletion or overexpression of HDAC1, a gene-silencing enzyme, to test whether HDAC1 drives liver fat buildup by lowering KLF3 and so altering PPARγ, a regulator of fat storage.
- Test whether liver HDAC1 promotes the progression from fatty liver to NASH in mice by lowering KLF3 and boosting c-Jun-driven immune-cell recruitment and inflammation.
- Determine whether excess glucose and saturated fatty acids add O-GlcNAc sugar tags to HDAC1. Test whether these tags stabilize the enzyme by blocking its ubiquitin tagging and breakdown by the proteasome.
More about the research
Instead they can act through epigenetics: chemical marks on DNA and on the proteins that package it, which turn genes up or down. This research asks how such marks link the environment to metabolic disease. One project studies the nerves that tell fat tissue to burn energy as heat. The other studies how an epigenetic enzyme in the liver senses excess nutrients and drives fatty liver disease.
Why it matters
Obesity and fatty liver disease are widespread and closely tied to type 2 diabetes. These projects could point to two new drug targets. UHMK1 in sympathetic nerves could help increase the body's own calorie burning through brown and beige fat, for the prevention and treatment of obesity. HDAC1 in the liver could be targeted to limit fat buildup, inflammation and scarring in people with non-alcoholic fatty liver disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Trayambak Pathak
Louisiana State University Health Sciences Center-New Orleans, LA·Physiology·Early-career
Test whether calcium entry through Orai3 channels drives mitochondrial heat production in brown adipose tissue to limit fat buildup, by measuring mitochondrial metabolism in Orai3 knockout 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.
Ren Zhang
Wayne State University, MI·Biochemistry
Determine whether MNADK, the mitochondrial NAD kinase, preserves liver energy balance and insulin sensitivity and reduces risk of NASH and type 2 diabetes, using genetically engineered mouse models.
The school
Georgia State University: 9 labs on PI Pages, $241M a year on research, 300 research doctorates a year.
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