Tatiana Kisseleva
University of Southern California, CA·Medicine & Clinical Research
Heavy drinking can scar the liver. Alcohol-associated liver disease (AALD) is a leading cause of cirrhosis, liver failure, liver cancer and liver transplantation, and there are no therapies for the scarring, called fibrosis, that it causes.
- Fields
Medicine & Clinical Research
Biology
Genetics
- Topics
alcohol-associated liver disease
alcoholic liver disease
liver fibrosis
- Grants
- 1 known grant, through Apr 2029
What they work on
- Identify genes that are more active in hepatic stellate cells (the liver's scar-forming cells) from human AALD livers than in normal, NAFL or NASH livers, using single-nucleus RNA sequencing (snRNA-seq).
- Map how chromatin, the packaging of DNA, is opened or closed in human stellate cells across alcohol-related and metabolic liver disease, using snATAC-seq to find regions that transcription factors can reach.
- Test whether silencing candidate genes with dsiRNA (short gene-blocking RNAs) prevents stellate cell activation, first in 2D human cell cultures and then in 3D human liver spheroids that model AALD.
- Delete candidate genes specifically in stellate cells of the mouse intragastric ethanol model of AALD to see whether fibrosis is reduced, and screen for small molecules that block the same genes.
More about the research
Fibrosis is driven by hepatic stellate cells (HSCs). These liver cells, once activated, turn into myofibroblasts, cells that lay down scar tissue. Mouse models have shown how HSCs behave, but little is known about HSCs in human AALD. It is also unknown whether they differ from HSCs in NASH, a fatty liver disease linked to metabolism that also causes fibrosis.
Why it matters
Alcohol-associated liver disease is a major cause of cirrhosis, liver failure, liver cancer and liver transplants, and no treatment currently stops the liver scarring it causes. By pinpointing genes that switch on scar-forming stellate cells specifically in alcohol-related disease, and small molecules that might block them, this work could point to new drug targets for patients with alcohol-induced liver fibrosis.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Hongxue Shi
Louisiana State University Health Sciences Center-Shreveport, LA·Medicine & Clinical Research·Early-career
Test whether loss of TIM4, a macrophage receptor that captures apoptotic cells, impairs clearance of dying liver cells and speeds NASH fibrosis, by deleting or restoring macrophage TIM4 in NASH mice.
Jennifer Chen
University of California-San Francisco, CA·Medicine & Clinical Research
Determine how ceramide inhibits YAP/TAZ, signaling proteins of the Hippo growth-control pathway, in hepatic stellate cells, using gain- and loss-of-function experiments and mice lacking acid ceramidase in these cells.
Jian-Min Yuan
University of Pittsburgh, PA·Public Health & Epidemiology
Enroll and follow at least 1,000 patients with non-alcoholic fatty liver disease and advanced fibrosis, tracking liver stiffness by transient elastography every six months for up to five years.
The school
University of Southern California: 47 labs on PI Pages, $1.3B a year on research, 882 research doctorates a year.
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