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Article ; Online: Patients, cells, and organelles: the intersection of science and serendipity.

Larusso, Nicholas F

2011 Volume 53, Issue 5, Page(s) 1417–1426

MeSH term(s)	Anecdotes as Topic ; Biomedical Research/history ; Cells ; Gastroenterology/history ; History, 20th Century ; History, 21st Century ; New York ; Organelles ; Patients
Language	English
Publishing date	2011-03-17
Publishing country	United States
Document type	Autobiography ; Biography ; Historical Article ; Journal Article ; Portrait ; Research Support, N.I.H., Extramural
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.24297
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Article ; Online: Polycystic Liver Disease: The Benefits of Targeting cAMP.

Larusso, Nicholas F / Masyuk, Tatyana V / Hogan, Marie C

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2016 Volume 14, Issue 7, Page(s) 1031–1034

MeSH term(s)	Cysts ; Humans ; Liver Diseases ; Polycystic Kidney, Autosomal Dominant
Language	English
Publishing date	2016
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2016.03.008
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Article ; Online: Genetics, pathobiology and therapeutic opportunities of polycystic liver disease.

Olaizola, Paula / Rodrigues, Pedro M / Caballero-Camino, Francisco J / Izquierdo-Sanchez, Laura / Aspichueta, Patricia / Bujanda, Luis / Larusso, Nicholas F / Drenth, Joost P H / Perugorria, Maria J / Banales, Jesus M

Nature reviews. Gastroenterology & hepatology

2022 Volume 19, Issue 9, Page(s) 585–604

Abstract: Polycystic liver diseases (PLDs) are inherited genetic disorders characterized by progressive development of intrahepatic, fluid-filled biliary cysts (more than ten), which constitute the main cause of morbidity and markedly affect the quality of life. ... ...

Abstract	Polycystic liver diseases (PLDs) are inherited genetic disorders characterized by progressive development of intrahepatic, fluid-filled biliary cysts (more than ten), which constitute the main cause of morbidity and markedly affect the quality of life. Liver cysts arise in patients with autosomal dominant PLD (ADPLD) or in co-occurrence with renal cysts in patients with autosomal dominant or autosomal recessive polycystic kidney disease (ADPKD and ARPKD, respectively). Hepatic cystogenesis is a heterogeneous process, with several risk factors increasing the odds of developing larger cysts. Depending on the causative gene, PLDs can arise exclusively in the liver or in parallel with renal cysts. Current therapeutic strategies, mainly based on surgical procedures and/or chronic administration of somatostatin analogues, show modest benefits, with liver transplantation as the only potentially curative option. Increasing research has shed light on the genetic landscape of PLDs and consequent cholangiocyte abnormalities, which can pave the way for discovering new targets for therapy and the design of novel potential treatments for patients. Herein, we provide a critical and comprehensive overview of the latest advances in the field of PLDs, mainly focusing on genetics, pathobiology, risk factors and next-generation therapeutic strategies, highlighting future directions in basic, translational and clinical research.
MeSH term(s)	Cysts ; Humans ; Kidney Diseases, Cystic ; Liver ; Liver Diseases ; Quality of Life
Language	English
Publishing date	2022-05-13
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/s41575-022-00617-7
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Article ; Online: The role of cilia in the regulation of bile flow.

Larusso, Nicholas F / Masyuk, Tetyana V

Digestive diseases (Basel, Switzerland)

2011 Volume 29, Issue 1, Page(s) 6–12

Abstract: Cholangiocytes, the epithelial cells lining intrahepatic bile ducts, are ciliated cells. Each cholangiocyte has a primary cilium consisting of (i) a microtubule-based axoneme and (ii) the basal body, centriole-derived, microtubule-organizing center from ... ...

Abstract	Cholangiocytes, the epithelial cells lining intrahepatic bile ducts, are ciliated cells. Each cholangiocyte has a primary cilium consisting of (i) a microtubule-based axoneme and (ii) the basal body, centriole-derived, microtubule-organizing center from which the axoneme emerges. Primary cilia in cholangiocytes were described decades ago, but their physiological and pathophysiological significance remained unclear until recently. We now recognize that cholangiocyte cilia extend from the apical plasma membrane into the bile duct lumen and, as such, are ideally positioned to detect changes in bile flow, bile composition and bile osmolality. These sensory organelles act as cellular antennae that can detect and transmit signals that influence cholangiocyte function. Indeed, recent data show that cholangiocyte primary cilia can activate intracellular signaling pathways when they sense modifications in the flow, molecular constituents and osmolarity of bile. Their ability to sense and transmit signals depends on the participation of a growing number of specific ciliary-associated proteins that act as receptors, channels and transporters. Cholangiocyte cilia, in addition to being important in normal biliary physiology, likely contribute to the cholangiopathies when their normal structure or function is disturbed. Indeed, the polycystic liver diseases that occur in combination with autosomal dominant and recessive polycystic kidney disease (i.e. ADPKD and ARPKD) are two important examples of such conditions. Recent insights into the role of cholangiocyte cilia in cystic liver disease using in vitro and animal models have already resulted in clinical trials that have influenced the management of cystic liver disease.
MeSH term(s)	Animals ; Bile/metabolism ; Bile Ducts/cytology ; Bile Ducts/metabolism ; Biological Transport ; Cilia/metabolism ; Cilia/ultrastructure ; Humans ; Models, Biological
Language	English
Publishing date	2011-06-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	632798-9
ISSN	1421-9875 ; 0257-2753
ISSN (online)	1421-9875
ISSN	0257-2753
DOI	10.1159/000324121
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Article ; Online: Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases.

Masyuk, Anatoliy I / Masyuk, Tatyana V / Larusso, Nicholas F

Journal of hepatology

2013 Volume 59, Issue 3, Page(s) 621–625

Abstract: Exosomes are small (30-100 nm in diameter) extracellular membrane-enclosed vesicles released by different cell types into the extracellular space or into biological fluids by exocytosis as a result of fusion of intracellular multivesicular bodies with ... ...

Abstract	Exosomes are small (30-100 nm in diameter) extracellular membrane-enclosed vesicles released by different cell types into the extracellular space or into biological fluids by exocytosis as a result of fusion of intracellular multivesicular bodies with the plasma membrane. The primary function of exosomes is intercellular communication with both beneficial (physiological) and harmful (pathological) potential outcomes. Liver cells are exosome-releasing cells as well as targets for endogenous exosomes and exosomes derived from cells of other organs. Despite limited studies on liver exosomes, initial observations suggest that these vesicles are important in liver physiology and pathophysiology. In this review, we briefly summarize the recent findings on liver exosomes, their functions and significance for novel diagnostic and therapeutic approaches.
MeSH term(s)	Animals ; Cell Communication ; Exocytosis ; Exosomes/physiology ; Exosomes/ultrastructure ; Humans ; Liver/physiology ; Liver/ultrastructure ; Liver Diseases/diagnosis ; Liver Diseases/etiology ; Liver Diseases/therapy ; Signal Transduction
Language	English
Publishing date	2013-04-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2013.03.028
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Article: Cholangiocyte biology.

Tietz, Pamela S / Larusso, Nicholas F

Current opinion in gastroenterology

2006 Volume 22, Issue 3, Page(s) 279–287

Abstract: Purpose of review: Cholangiocytes are increasingly recognized as biologically important epithelia because of the diverse array of cellular processes in which they participate. Collectively, these processes define normal function and, when disturbed, ... ...

Abstract	Purpose of review: Cholangiocytes are increasingly recognized as biologically important epithelia because of the diverse array of cellular processes in which they participate. Collectively, these processes define normal function and, when disturbed, account for abnormalities that cause disease. Advances in animal models and sophisticated technology in imaging and gene silencing have led to substantial progress in defining the roles that cholangiocytes play in signaling, transport of water, ions and solutes, and alterations that result in cholestasis. The pace of advances in technology justifies a yearly summary to identify trends, and inform the readership of the most significant developments in cholangiocyte biology. Recent findings: The main areas of recent progress include insights into the molecular mechanisms of bile secretion and the development of new experimental models and technologies. Major advances have also included the identification of novel roles for receptors and better understanding of mechanistic pathways and biologic processes. Summary: Understanding the key mechanistic and biologic processes in cholangiocytes is required to generate hypotheses and therapies relevant to disease. This compendium of current activities in cholangiocyte biology may promote collegial sharing and exchange of novel concepts, ideas, reagents and probes, thereby promoting positive advances in the field.
MeSH term(s)	Animals ; Bile/secretion ; Bile Duct Diseases/pathology ; Bile Duct Diseases/physiopathology ; Bile Ducts/cytology ; Cell Proliferation ; Cytoprotection ; Humans
Language	English
Publishing date	2006-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632571-3
ISSN	1531-7056 ; 0267-1379
ISSN (online)	1531-7056
ISSN	0267-1379
DOI	10.1097/01.mog.0000218965.78558.bc
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Article: Cholangiocyte biology.

Tietz, Pamela / Larusso, Nicholas F

Current opinion in gastroenterology

2006 Volume 18, Issue 3, Page(s) 360–365

Abstract: Due in part to the recent development of new experimental models, cholangiocytes--the epithelial cells that line the bile ducts--are increasingly recognized as important transporting epithelia actively involved in the absorption and secretion of water, ... ...

Abstract	Due in part to the recent development of new experimental models, cholangiocytes--the epithelial cells that line the bile ducts--are increasingly recognized as important transporting epithelia actively involved in the absorption and secretion of water, ions, and solutes. New biologic concepts have emerged including the identification and topography of receptors and flux proteins involved in the molecular mechanisms of ductal bile secretion. Individually isolated or perfused bile duct units from livers of rats and mice serve as new, physiologically relevant in vitro models to study cholangiocyte transport. Biliary tree dimensions and novel insights into anatomic remodeling of proliferating bile ducts have emerged from three-dimensional reconstruction using computed tomographic scanning and sophisticated software. Moreover, new pathologic concepts have arisen regarding the interaction of cholangiocytes with pathogens. These concepts may provide the framework for new therapies for the cholangiopathies, a group of important hepatobiliary diseases in which cholangiocytes are the target cell.
Language	English
Publishing date	2006-09-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	632571-3
ISSN	1531-7056 ; 0267-1379
ISSN (online)	1531-7056
ISSN	0267-1379
DOI	10.1097/00001574-200205000-00010
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Article: Examining the increased IgM production and ursodeoxycholic acid treatment in PBC.

Lazaridis, Konstantinos N / Larusso, Nicholas F

Gastroenterology

2005 Volume 128, Issue 2, Page(s) 498–500

MeSH term(s)	Cholagogues and Choleretics/therapeutic use ; Humans ; Immunoglobulin M/blood ; Immunologic Memory ; Liver Cirrhosis, Biliary/blood ; Liver Cirrhosis, Biliary/drug therapy ; Liver Cirrhosis, Biliary/immunology ; Ursodeoxycholic Acid/therapeutic use
Chemical Substances	Cholagogues and Choleretics ; Immunoglobulin M ; Ursodeoxycholic Acid (724L30Y2QR)
Language	English
Publishing date	2005-02
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2004.12.040
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Article ; Online: Primary sclerosing cholangitis: the gut-liver axis.

Tabibian, James H / O'Hara, Steven P / Larusso, Nicholas F

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2012 Volume 10, Issue 7, Page(s) 819; author reply 819–20

MeSH term(s)	Cholangitis, Sclerosing/complications ; Cholangitis, Sclerosing/epidemiology ; Female ; Humans ; Inflammatory Bowel Diseases/complications ; Inflammatory Bowel Diseases/epidemiology ; Male
Language	English
Publishing date	2012-07
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2012.01.024
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Zs.A 5836: Show issues

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Article ; Online: HDAC6 is overexpressed in cystic cholangiocytes and its inhibition reduces cystogenesis.

Gradilone, Sergio A / Habringer, Stefan / Masyuk, Tatyana V / Howard, Brynn N / Masyuk, Anatoliy I / Larusso, Nicholas F

The American journal of pathology

2014 Volume 184, Issue 3, Page(s) 600–608

Abstract: Polycystic liver disease (PLD) is a member of the cholangiopathies, a group of liver diseases in which cholangiocytes, the epithelia lining of the biliary tree, are the target cells. PLDs are caused by mutations in genes involved in intracellular ... ...

Abstract	Polycystic liver disease (PLD) is a member of the cholangiopathies, a group of liver diseases in which cholangiocytes, the epithelia lining of the biliary tree, are the target cells. PLDs are caused by mutations in genes involved in intracellular signaling pathways, cell cycle regulation, and ciliogenesis, among others. We previously showed that cystic cholangiocytes have abnormal cell cycle profiles and malfunctioning cilia. Because histone deacetylase 6 (HDAC6) plays an important role in both cell cycle regulation and ciliary disassembly, we examined the role of HDAC6 in hepatic cystogenesis. HDAC6 protein was increased sixfold in cystic liver tissue and in cultured cholangiocytes isolated from both PCK rats (an animal model of PLD) and humans with PLD. Furthermore, pharmacological inhibition of HDAC6 by Tubastatin-A, Tubacin, and ACY-1215 decreased proliferation of cystic cholangiocytes in a dose- and time-dependent manner, and inhibited cyst growth in three-dimensional cultures. Importantly, ACY-1215 administered to PCK rats diminished liver cyst development and fibrosis. In summary, we show that HDAC6 is overexpressed in cystic cholangiocytes both in vitro and in vivo, and its pharmacological inhibition reduces cholangiocyte proliferation and cyst growth. These data suggest that HDAC6 may represent a potential novel therapeutic target for cases of PLD.
MeSH term(s)	Anilides/pharmacology ; Anilides/therapeutic use ; Animals ; Bile Ducts, Intrahepatic/cytology ; Cell Proliferation ; Cells, Cultured ; Cilia/metabolism ; Cysts/drug therapy ; Cysts/metabolism ; Cysts/pathology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Histone Deacetylase 6 ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Histone Deacetylases/drug effects ; Histone Deacetylases/metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Hydroxamic Acids/therapeutic use ; Indoles/pharmacology ; Indoles/therapeutic use ; Liver/metabolism ; Liver/pathology ; Liver Diseases/drug therapy ; Liver Diseases/metabolism ; Liver Diseases/pathology ; Male ; Pyrimidines/pharmacology ; Pyrimidines/therapeutic use ; Rats ; Signal Transduction ; Time Factors
Chemical Substances	Anilides ; Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Indoles ; Pyrimidines ; tubacin (02C2G1D30D) ; tubastatin A (2XTSOX1NF8) ; HDAC6 protein, human (EC 3.5.1.98) ; HDAC6 protein, rat (EC 3.5.1.98) ; Histone Deacetylase 6 (EC 3.5.1.98) ; Histone Deacetylases (EC 3.5.1.98) ; ricolinostat (WKT909C62B)
Language	English
Publishing date	2014-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2013.11.027
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