Skip to Main Content

Michael Nathanson, MD, PhD

Gladys Phillips Crofoot Professor of Medicine (Digestive Diseases) and Professor of Cell Biology; Director, Yale Liver Center; Director, Center for Cell and Molecular Imaging

Research Summary

My laboratory studies the mechanisms and effects of calcium signals in polarized epithelia. One aspect of our work is to define how calcium signals are differentially regulated in the nucleus and cytoplasm. This involves identification of distinct calcium stores and release mechanisms in the nucleus, and we are examining whether and how these are activated selectively by growth factors. The second aspect of our work is to examine how calcium waves and other calcium signals regulate secretion in polarized epithelia. Calcium waves preferentially begin in, the apical region of most secretory epithelia, and we are in the process of defining the mechanisms responsible for this. We also are using an adenoviral antisense approach to understand the relative roles of each IP3 receptor isoform in regulating calcium signaling and secretion in vitro and in vivo. Another major focus is to examine intercellular communication of second messenger signals and to establish the mechanism by which gap junctions act in coordinating intercellular spread of Ca2+ waves in isolated pairs and triplets of cells.

Specialized Terms: Mechanisms and effects of calcium signals in polarized epithelia; Effect of spatial organization of calcium signals on organ function regulation; Factors that organize Ca2+ waves in hepatocytes; Organization and effects of Ca2+ waves in cholangiocytes; Mechanisms and effects of Ca2+ signals in the nucleus

Extensive Research Description

  • NIH P01 DK57751 (PI: M.H. Nathanson) 04/01/01-04/30/21 Title: Regulation of liver by nuclear calcium signaling Goals: The major goals of this project are to determine the mechanisms by which calcium is regulated in the nucleus of hepatocytes, and to determine the functional effects of nuclear calcium signals in liver. Dr. Nathanson directs Project 1 and the Administrative and Cell Imaging cores of this PPG.
  • NIH P30 DK34989 (PI: M.H. Nathanson) 09/01/84-08/31/20 (NCE pending) Title: Digestive Diseases Research Core Center (Yale Liver Center) Goals: Dr. Nathanson is Director of the Liver Center as well as of the Morphology and Administrative Core components of the Center. The major goals of the Morphology Core are to provide a multidisciplinary center where the research focus is liver structure, function and disease.
  • NIH R01 DK114041 (PI: M.H. Nathanson) 02/01/18-03/31/23 Title: Ca2+ waves in hepatocytes: Mechanisms and effects Goals: The major goals of this project are to determine the mechanisms by which the type 2 InsP3 receptor regulates calcium-mediated bile secretion by hepatocytes, and to determine the role that loss or mis-localization of this receptor plays in the pathogenesis of cholestatic liver disease.
  • NIH R01 DK112797 (PI: M.H. Nathanson) 09/01/17-08/31/22 Title: Molecular regulation of cholestasis in cholangiocytes. Goals: Major goals are to understand the role of type 3 inositol trisphosphate receptor function in cholestatic liver disease
  • NIH T32 DK007356 (PI: M.H. Nathanson) 7/1/84-6/30/24 Title: Investigative Training in Hepatology. Goals: This training grant provides 1) laboratory research training for physicians who have completed clinical training in Gastroenterology and are in preparation for careers as independent investigators in academic Hepatology and research training for recent Ph.D. graduates to prepare them for careers as independent investigators in basic liver-related research.

Coauthors

Research Interests

Cell Nucleus; Cell Biology; Digestive System Diseases; Liver; Calcium Signaling; Hepatocytes

Selected Publications

  • 219-LB: The Mitochondrial Calcium Uniporter Regulates Hepatic Lipid Accumulation and Mitochondrial OxidationLAMOIA T, HUBBARD B, GUERRA M, GOODMAN R, NATHANSON M, MOOTHA V, SHULMAN G. 219-LB: The Mitochondrial Calcium Uniporter Regulates Hepatic Lipid Accumulation and Mitochondrial Oxidation Diabetes 2022, 71 DOI: 10.2337/db22-219-lb.
  • AS080 Interaction between neutrophils and cholangiocytes causes cholestasis in alcoholic hepatitisTakeuchi M, Vidigal P, Guerra M, Hundt M, Robert M, Olave-Martinez M, Aoki S, Khamphaya T, Kersten R, Kruglov E, Banales J, Nathanson M, Weerachayaphorn J. AS080 Interaction between neutrophils and cholangiocytes causes cholestasis in alcoholic hepatitis Journal Of Hepatology 2020, 73: s58-s59. DOI: 10.1016/s0168-8278(20)30659-0.
  • Calcium Signaling in CholangiocytesAlpini G, Alvaro D, Marzioni M, LeSage G, LaRusso N, Hernandez E, Nathanson M. Calcium Signaling in Cholangiocytes 2020, 105-111. DOI: 10.1201/9780367813888-10.
  • Ca2+ Signaling in the LiverGuerra M, Leite M, Nathanson M. Ca2+ Signaling in the Liver 2020, 496-508. DOI: 10.1002/9781119436812.ch40.
  • Signaling pathways in biliary epithelial cellsLeite M, Guerra M, Andrade V, Nathanson M. Signaling pathways in biliary epithelial cells 2015, 15-33. DOI: 10.1002/9781118663387.ch2.
  • Something old, something newNathanson M. Something old, something new Hepatology 2011, 55: 1-2. DOI: 10.1002/hep.24817.
  • Low pH Inhibits Gap Junction Communication in the Pancreatic Acinar CellReed A, Husain S, Gorelick F, Nathanson M. Low pH Inhibits Gap Junction Communication in the Pancreatic Acinar Cell Gastroenterology 2011, 140: s-385. DOI: 10.1016/s0016-5085(11)61577-1.
  • Mitochondrial Calcium Regulates Liver Regeneration Through Modulation of ApoptosisMelo F, Guerra M, Andrade V, Fonseca E, Souza-Fagundes E, Menezes G, de Paula A, Nathanson M, Leite M. Mitochondrial Calcium Regulates Liver Regeneration Through Modulation of Apoptosis Gastroenterology 2011, 140: s-472. DOI: 10.1016/s0016-5085(11)61941-0.
  • 537 The Epidermal Growth Factor Receptor (EGFR) Reaches the Nucleus via a Caveolin-Dependent PathwayRodrigues M, Campos A, Goes A, Nathanson M, Gomes D. 537 The Epidermal Growth Factor Receptor (EGFR) Reaches the Nucleus via a Caveolin-Dependent Pathway Gastroenterology 2010, 138: s-790. DOI: 10.1016/s0016-5085(10)63640-2.
  • T1935 Low pH Enhances Calcium Signaling in the Pancreatic Acinar CellChaudhuri A, Shah A, Husain S, Gorelick F, Nathanson M. T1935 Low pH Enhances Calcium Signaling in the Pancreatic Acinar Cell Gastroenterology 2010, 138: s-610. DOI: 10.1016/s0016-5085(10)62812-0.
  • 538 Regulation of MRP2 by Calcium SignalingGuerra M, Cruz L, Kruglov E, Garcia C, Chen J, Nathanson M. 538 Regulation of MRP2 by Calcium Signaling Gastroenterology 2010, 138: s-790. DOI: 10.1016/s0016-5085(10)63641-4.
  • 539 Inositol 1,4,5-Trisphosphate Receptor Type 2 Modulates Bsep Activity in HepatocytesKruglov E, Gautam S, Nathanson M. 539 Inositol 1,4,5-Trisphosphate Receptor Type 2 Modulates Bsep Activity in Hepatocytes Gastroenterology 2010, 138: s-791. DOI: 10.1016/s0016-5085(10)63642-6.
  • S1426: High-Definition In-Vivo Probe-Based Confocal Laser Endomicroscopy of the Common Bile DuctShieh F, Nathanson M, Drumm H, Jamidar P. S1426: High-Definition In-Vivo Probe-Based Confocal Laser Endomicroscopy of the Common Bile Duct Gastrointestinal Endoscopy 2010, 71: ab158-ab159. DOI: 10.1016/j.gie.2010.03.200.
  • Signaling Pathways in Biliary Epithelial CellsLeite M, Andrade V, Nathanson M. Signaling Pathways in Biliary Epithelial Cells 2009, 25-39. DOI: 10.1007/978-3-642-00150-5_2.
  • Ca2+ Signaling in the LiverLeite F, Guerra M, Nathanson M. Ca2+ Signaling in the Liver 2009, 485-510. DOI: 10.1002/9780470747919.ch32.
  • Probe-based Laser Confocal Endomicroscopy for the Diagnosis of Biliary MalignanciesLoeser C, Nathanson M, Jamidar P. Probe-based Laser Confocal Endomicroscopy for the Diagnosis of Biliary Malignancies The American Journal Of Gastroenterology 2009, 104: s75-s76. DOI: 10.14309/00000434-200910003-00193.
  • 87 Nucleoplasmic Calcium Regulates Proliferation of Hepatocytes Through Legumain and Reticulon4Andrade V, Jardim C, Melo F, Silva W, Nathanson M, Ortega J, Leite M. 87 Nucleoplasmic Calcium Regulates Proliferation of Hepatocytes Through Legumain and Reticulon4 Gastroenterology 2009, 136: a-792. DOI: 10.1016/s0016-5085(09)63653-2.
  • 521 CYTOSOLIC CALCIUM MEDIATES LIVER REGENERATION IN THE RATLagoudakis L, Garcin I, Nahum K, Combettes L, Nathanson M, Tordjmann T. 521 CYTOSOLIC CALCIUM MEDIATES LIVER REGENERATION IN THE RAT Journal Of Hepatology 2008, 48: s196. DOI: 10.1016/s0168-8278(08)60523-1.
  • Functions of the LiverRenato P, Correa A, Nathanson M, Wolkoff A, Novikoff P, Thevananther S, Karpen S, Elferink R, Püschel G, Stieger B. Functions of the Liver 2007, 89-128. DOI: 10.1002/9780470691861.ch2b.
  • Corrigendum to “Calcium release from ryanodine receptors in the nucleoplasmic reticulum” [Cell Calcium 39 (2006) 65–73]Marius P, Guerra M, Nathanson M, Ehrlich B, Leite M. Corrigendum to “Calcium release from ryanodine receptors in the nucleoplasmic reticulum” [Cell Calcium 39 (2006) 65–73] Cell Calcium 2006, 39: 551. DOI: 10.1016/j.ceca.2006.02.001.
  • DISTINCT CALCIUM SIGNALS REGULATE PANCREATIC ZYMOGEN ACTIVATIONHusain S, Grant W, Kolodecik T, Nathanson M, Gorelick F. DISTINCT CALCIUM SIGNALS REGULATE PANCREATIC ZYMOGEN ACTIVATION Pancreas 2005, 31: 446-447. DOI: 10.1097/01.mpa.0000193686.75459.3a.
  • Signaling Pathways in Biliary Epithelial CellsLeite M, Nathanson M. Signaling Pathways in Biliary Epithelial Cells 2005, 17-26. DOI: 10.1007/3-540-27194-5_2.
  • O0093 THE RYANODINE RECEPTOR MODULATES SECRETAGOGUE STIMULATED PANCREATIC ZYMOGEN ACTIVATIONHusain S, Prasad P, Kolodecik T, Nathanson M, Gorelick F. O0093 THE RYANODINE RECEPTOR MODULATES SECRETAGOGUE STIMULATED PANCREATIC ZYMOGEN ACTIVATION Journal Of Pediatric Gastroenterology And Nutrition 2004, 39: s43-s44. DOI: 10.1097/00005176-200406001-00095.
  • Gap Junctions in the LiverEchevarría W, Nathanson M. Gap Junctions in the Liver 2004, 36-47. DOI: 10.1007/978-1-4419-9034-1_4.
  • Loss of inositol 1,4,5-trisphosphate receptors from cholangiocytes is a final common pathway for cholestasisShibao K, Hirata K, Robert M, Nathanson M. Loss of inositol 1,4,5-trisphosphate receptors from cholangiocytes is a final common pathway for cholestasis Gastroenterology 2003, 124: a692. DOI: 10.1016/s0016-5085(03)83502-3.
  • Ca2+ in the nucleus is independently regulated and has distinct effects on protein kinase C (PKC) in a liver cell lineGuerra M, de Fatima Leite M, Echevarria W, Nathanson M. Ca2+ in the nucleus is independently regulated and has distinct effects on protein kinase C (PKC) in a liver cell line Gastroenterology 2003, 124: a689. DOI: 10.1016/s0016-5085(03)83484-4.
  • Chronic Viral Hepatitis: Diagnosis and Therapeutics.Pusl T, Nathanson M. Chronic Viral Hepatitis: Diagnosis and Therapeutics. Journal Of Clinical Gastroenterology 2002, 34: 496. DOI: 10.1097/00004836-200204000-00033.
  • Transplantation of the Liver, Third Edition.Pusl T, Nathanson M. Transplantation of the Liver, Third Edition. Journal Of Clinical Gastroenterology 2001, 33: 347-348. DOI: 10.1097/00004836-200110000-00026.
  • Stimulation of ATP secretion in the liver by therapeutic bile acidsNATHANSON M, BURGSTAHLER A, MASYUK A, LaRUSSO N. Stimulation of ATP secretion in the liver by therapeutic bile acids Biochemical Journal 2001, 358: 1-5. DOI: 10.1042/bj3580001.
  • Molecular identification of a primitive P2Y ATP receptor in liver from the little skate Raja erinaceaDranoff J, O’Neill A, Cai S, Franco A, Connelly G, Ballatori N, Boyer J, Nathanson M. Molecular identification of a primitive P2Y ATP receptor in liver from the little skate Raja erinacea Gastroenterology 2000, 118: a911. DOI: 10.1016/s0016-5085(00)85777-7.
  • CA2+ waves require sequential activation of inositol 1,4,5-trisphosphate receptors, then ryanodine receptors in pancreatic acinar cellLeite M, Salgado A, Franco A, Burgstahler A, Nathanson M. CA2+ waves require sequential activation of inositol 1,4,5-trisphosphate receptors, then ryanodine receptors in pancreatic acinar cell Gastroenterology 2000, 118: a875. DOI: 10.1016/s0016-5085(00)85639-5.
  • Expression and subcellular localization of the ryanodine receptor in rat pancreatic acinar cellsLEITE M, DRANOFF J, Ling G, NATHANSON M. Expression and subcellular localization of the ryanodine receptor in rat pancreatic acinar cells Biochemical Journal 1999, 337: 305-309. DOI: 10.1042/bj3370305.
  • Intercellular Calcium Signaling in LiverNathanson M, Fallon M, Burgstahler A, Mennone A, Schlosser S, Gonzalez C, Sáez J. Intercellular Calcium Signaling in Liver 1997, 469-481. DOI: 10.1007/978-1-4899-1795-9_27.
  • Characterization and function of ATP receptors on hepatocytes from the little skate Raja erinaceaNathanson M, Mariwalla K. Characterization and function of ATP receptors on hepatocytes from the little skate Raja erinacea Gastroenterology 1995, 108: a1132. DOI: 10.1016/0016-5085(95)28828-7.

Clinical Trials

ConditionsStudy Title
Hepatitis; HIV/AIDS; Immune System; Infectious DiseasesScreening In Anticipation of Future Research