SUMMARY
The long-standing research interest of Nicholas F. LaRusso, M.D., is in hepatic epithelial cell function and dysfunction, with a focus principally on the epithelial cells that line the bile ducts. The epithelial cells that line the bile ducts are called cholangiocytes and they have biological and clinical importance. The cholangiocytes constitute the primary target of a group of diseases of diverse etiologies called cholangiopathies. Dr. LaRusso also works on identifying new therapeutic targets and developing new hypotheses and new techniques to understand the mechanisms driving these conditions.
Dr. LaRusso's research program has had continuous support from the National Institutes of Health for over four decades. His support includes a Method to Extend Research in Time Award, attesting to the program's relevance and exceptionalism.
Focus areas
- Cholangiociliopathies. The cholangiociliopathies are a group of incurable genetic diseases characterized by cysts in the liver with or without associated renal cysts. Dr. LaRusso's research team evaluates the hypothesis that overexpression of TGR5, a bile acid membrane receptor, in cystic cholangiocytes induces autophagy of discrete miRNAs via the cyclic adenosine monophosphate signaling pathway, thereby increasing expression of cell cycle proteins and promoting hepatic cyst formation known as cystogenesis. Autophagy is the body's way of removing damaged cells. MiRNAs are small ribonucleic acid molecules.
- Primary sclerosing cholangitis (PSC). Dr. LaRusso's research team is working to define the mechanisms, consequences and pathological outcomes of cholangiocyte senescence in the syndrome PSC.
While cholangiocytes play an integral role in the cholangiopathies, including PSC, it is not known how cholangiocyte signaling contributes to the initiation and progression of PSC. Dr. LaRusso's team hypothesizes that persistent insults from outside factors induce TLR-dependent activation of Ras/MAPK, promoting let-7i miRNA-dependent cholangiocyte senescence and the senescence-associated secretory phenotype. This phenotype contributes to the fibroinflammatory features of PSC.
Significance to patient care
Dr. LaRusso's clinical activities are linked to his research program. Indeed, many of the ideas and questions addressed in his lab are direct outgrowths of his interactions with people who have cholangiopathies. Thus, understanding the pathogenesis of cholangiopathies facilitates the development of new therapies targeting the key molecules, processes and organelles involved in these conditions.
Research in Dr. LaRusso's lab has already resulted in new and effective pharmacological treatments for polycystic liver diseases and is on the verge of breakthrough treatments for other cholangiopathies.
Professional highlights
- Charles H. Weinman Endowed Professor, Mayo Clinic, 2006-present.
- Mayo Clinic Alumni Association, Mayo Clinic:
- Distinguished Alumnus Award, 2022.
- Professional Achievement Award, 2009.
- American Gastroenterological Association:
- Julius Friedenwald Medal, 2014.
- Distinguished Mentor Award, 2005.
- Distinguished Achievement Award, 2001.
- Chair, Department of Internal Medicine, Mayo Clinic, 1999-2008.
- Distinguished Achievement Award, American Association for the Study of Liver Diseases, 2003.
- Honorary fellow, Royal College of Physicians of Ireland, 2001.
- Chair, Division of Gastroenterology and Hepatology, Mayo Clinic, 1990-1999.
- Distinguished Investigator Award, Mayo Clinic College of Medicine, Mayo Clinic, 1993.
- Method to Extend Research in Time Award, National Institutes of Health, 1991.