Research
Primary sclerosing cholangitis
Primary sclerosing cholangitis
Primary sclerosing cholangitis
In this image, imaging mass cytometry shows liver tissue from a patient with primary sclerosing cholangitis. The cyan color shows positivity for cytokeratin. The magenta color shows an infiltration of macrophages.
Research projects in the Cholangiopathies Laboratory focus on complex liver diseases that currently have limited treatment options. Dr. LaRusso's ultimate goal is to expand treatment options by advancing knowledge about primary sclerosing cholangitis and other types of cholangiopathies.
Primary sclerosing cholangitis
Primary sclerosing cholangitis is a rare, incurable, complex autoimmune disease of the bile ducts. Our research team has proposed that primary sclerosing cholangitis likely develops and progresses through the interaction of predisposing genetic factors and environmental exposures. This interaction influences biological processes that occur at the level of the gut and the biliary tree, including the intestinal microbiome, and through dynamic changes in the cholangiocyte phenotype, including its epigenome.
Research from our lab showed that in people with primary sclerosing cholangitis, cholangiocytes undergo the process of cellular senescence, a phenotype linked to both cell cycle arrest and vigorous secretion of various bioactive molecules. This process is called the senescence-associated secretory phenotype. Cells with this phenotype can modify their microenvironment by inducing proinflammatory and fibrotic cellular reactions and accelerating neoplastic transformation.
Our work is providing mechanistic information about the pathways of senescence and senescence-associated secretory phenotype, inflammation, and fibrosis in primary sclerosing cholangitis. Our work has substantial therapeutic implications for the development and testing of drugs called senolytics that selectively kill senescent cells.
Patents
Dr. LaRusso's research in the Cholangiopathies Laboratory and his collaboration with other investigators on the treatment of liver diseases has resulted in several U.S. patents. Here are Dr. LaRusso's current patents.
| Investigator |
Patent title |
Patent number |
Patent date |
| Nicholas F. LaRusso, Tetyana V. Masyuk and Melissa A. Muff |
Treating Liver Diseases |
U.S. Patent 9,012,392 |
April 21, 2015 |
| Nicholas F. LaRusso and Anatoliy I. Masyuk |
Targeting TGR5 to Treat Disease |
U.S. Patent Draft 070391396WO1 |
Oct. 3, 2014 |
| Nicholas F. LaRusso, Tetyana V. Masyuk and Melissa A. Muff |
Treating Liver Diseases |
U.S. Patent 8,232,241 |
July 31, 2012 |
| Nicholas F. LaRusso |
Treatment of Proliferation of Bile Duct Epithelium |
U.S. Patent 5,583,104 |
Dec. 10, 1996 |