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 (cholangiocytes) because of their biologic and clinical importance: They constitute the primary target of a group of important diseases of diverse etiologies (cholangiopathies). Dr. LaRusso also works to develop new hypotheses and novel techniques to study cholangiocytes and cholangiopathies.
Dr. LaRusso's research program has had continuous support from the National Institutes of Health for over three decades, including a MERIT Award attesting to the program's relevance.
- 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 is testing the hypothesis that overexpression of TGR5, a bile acid membrane receptor, in cystic cholangiocytes induces autophagy of discrete miRNAs (miRNAutophagy) via the cyclic adenosine monophosphate (cAMP) signaling pathway, thereby increasing expression of cell cycle proteins and promoting hepatic cystogenesis.
Primary sclerosing cholangitis (PSC). Dr. LaRusso's research team is working to define the mechanisms, consequences and pathologic outcomes of cholangiocyte senescence in the syndrome PSC.
While the cholangiocyte plays 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 exogenous insult induces TLR-dependent activation of Ras/MAPK, promoting let-7i miRNA-dependent cholangiocyte senescence and the senescence-associated secretory phenotype (SASP), a phenotype that contributes to the fibroinflammatory features of PSC.
For more information, please visit Dr. LaRusso's laboratory page.
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 patients. Thus, understanding the pathogenesis of the cholangiopathies facilitates the development of novel therapies targeting key molecules, processes and organelles involved in these diseases.
Research in Dr. LaRusso's lab has already resulted in new and effective pharmacologic treatments for the polycystic liver diseases and is on the verge of breakthrough treatments for other cholangiopathies.
- Member, board of directors, VitalHealth Software (chair), 2014-present, Oklahoma State University Center for Health System Innovations, 2013-present; Delos Living, 2012-present
- Julius Friedenwald Medal, American Gastroenterological Association, 2014
- William Cullen Bryant Award, New York Medical College, 2013
- Professional Achievement Award, Mayo Clinic Alumni Association, 2009
- Chair, Department of Internal Medicine, 1999-2008; Division of Gastroenterology and Hepatology, 1990-1999, Mayo Clinic
- Alumnus of the Year, Brooklyn Preparatory School, 2005
- Distinguished Mentor Award, American Gastroenterological Association, 2005
- Distinguished Achievement Award, American Association for the Study of Liver Diseases, 2003
- Distinguished Achievement Award, American Gastroenterological Association, 2001
- Honorary Fellow, Royal College of Physicians of Ireland, 2001
- Medal of Honor, New York Medical College Alumni Association, 2000
- Distinguished Investigator Award, Mayo Clinic College of Medicine, 1993
- Distinguished Achievement Award, Alumni Association, New York Medical College, 1991
- MERIT Award, National Institutes of Health, 1991