Department of Physiology, McGill University, Montreal, Quebec, Canada
 



 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

LAB MEMBERS:  Dr. John Hanrahan


 

Dr. John William Hanrahan

Professor of Physiology


 
INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY
Dalhousie Univ., Halifax, Nova Scotia B.Sc.(Hon.) 1976 Biology
Univ. British Columbia, Vancouver, B.C. Ph.D. 1982 Zoology


   A.  P
OSITIONS AND HONOURS

   Positions and Employment

1982-1985    Postdoctoral Fellow, Department of Physiology, Yale Univ. School of Medicine
1985-1986 Research Associate, Department of Physiology, Yale Univ. School of Medicine
1986-1991 Assistant Professor, Department of Physiology, McGill University
1991-present Medical Scientist, Montreal Chest Institute, McGill University Health Centre
1991-present Associate Member, Meakins-Christie Laboratories, McGill University Health Centre 
1991-present Associate Professor, Department of Physiology, McGill University
1999-present Professor, Department of Physiology, McGill University


   Other Experience and Professional Memberships

1982-present American Physiological Society
1990-1992 Editorial Board - Am. J. Physiol. (Renal, Fluid and Electrolyte Physiol. )
1991-1994 Scientific Council, Kidney Foundation of Canada
1994-1995 Graduate Scholarships Committee, Fonds pour la formation de chercheurs et l'aide à la recherche, Québec
1995-1998 Cell Physiology Committee, Medical Research Council of Canada
1995-2001 Editorial Board, Am. J. Physiol. (Cell Physiol.)
1998-2001 Chair, Cell Physiology Committee, Medical Research Council of Canada/Canadian Institutes of Health Research
1998-2003 Medical/Scientific Advisory Committee, Canadian Cystic Fibrosis Foundation
1999-2003  Executive Committee, Canadian Cystic Fibrosis Foundation
1999-present  Reviewing Editor, Journal of Physiology


  
Honours

1971 Entrance Scholarship, Dalhousie University, Halifax, Nova Scotia
1980 Scholarship, Natural Sciences and Engineering Research Council Canada
1982 Thesis Award, Outstanding Ph.D. of 1982, Canadian Society of Zoologists
1982-1984 NATO Fellowship, Yale University School of Medicine
1984 Brown-Coxe Fellowship, Yale University School of Medicine, declined
1984-1985 Post-doc Fellowship, Medical Research Council Canada, Yale University
1987-1991 Research Scholarship, Medical Research Council Canada
1992 J.A.F. Stevenson Professor, Canadian Physiological Society
1992 Milbury Fellow, Mount Desert Island Biological Laboratory
1993 Senior Scientist II, Fonds de la recherche en santé du Québec
1994-1998 Scientist, Medical Research Council Canada
1999-present Senior Scientist, Medical Research Council Canada
2001 Visiting Professor, Burroughs-Wellcome Foundation
2003 Benjamin Meaker Visiting Professorship, University of Bristol, UK

  

B. SELECTED PEER-REVIEWED PUBLICATIONS
(Publications selected from 70 peer-reviewed publications)

 

Hanrahan JW, Alles WP and Lewis SA 1985.  Single anion-selective channels in basolateral membrane of a mammalian tight epithelium.  Proc. Natl. Acad. Sci. (USA) 82: 7791-7795.

Lewis SA and Hanrahan JW 1990.  Physiological approaches for studying urinary bladder epithelium.  Meth. Enzymol.  192:632-650.

Tabcharani JA, Low W, Elie D and Hanrahan JW 1990.  Low-conductance chloride channel activated by cAMP in the epithelial cell line T84.  FEBS Lett. 270: 157-164.

Kartner N, Hanrahan JW, Jensen TJ, Naismith AL, Sun S, Ackerley CA, Reyes EF, Tsui LC, Rommens JM, Bear CE and Riordan JR 1991.  Expression of the cystic fibrosis gene in non-epithelial invertebrate cells produces a regulated anion conductance.  Cell 64: 681-691.

Tabcharani JA, Chang X-B, Riordan JR and Hanrahan JW 1991.  Phosphorylation-regulated Cl- channel in CHO cells stably expressing the cystic fibrosis gene.  Nature 352: 628-631.

Bear CE, Duguay F, Naismith AL, Kartner N, Hanrahan JW and Riordan JR 1991.  Cl- channel activity in Xenopus oocytes expressing the cystic fibrosis gene.  J. Biol. Chem. 266: 19142-19145.

Tabcharani JA, Chang X-B, Riordan JR and Hanrahan JW 1992.  The CFTR chloride channel: Iodide block and permeation.  Biophys. J. 62: 1-4.

Chang X-B, Tabcharani JA, Hou Y-X, Jensen TJ, Kartner N, Alon N, Hanrahan JW and Riordan JR 1993.  Protein kinase A (PKA) still activates CFTR chloride channel after mutagenesis of all ten PKA consensus phosphorylation sites.  J. Biol. Chem. 268: 11304-11311.

Tabcharani JA, Rommens JM, Hou Y-X, Chang X-B, Tsui L-C, Riordan JR and Hanrahan JW 1993. Multi-ion pore behaviour in the CFTR chloride channel.  Nature 366: 79-82.

Becq F, Jensen TJ, Chang X-B, Savoia A, Rommens JM, Tsui L-C, Buchwald M, Riordan JR and Hanrahan JW 1994.  Phosphatase inhibitors activate normal and defective CFTR chloride channels.  Proc. Natl. Acad. Sci. USA 91: 9160-9164.

Seibert FS, Tabcharani JA, Chang X-B, Dulhanty AM, Mathews CJ, Hanrahan JW and Riordan JR 1995.  cAMP-dependent protein kinase-mediated phosphorylation of cystic fibrosis transmembrane conductance regulator residue ser-753 and its role in channel activation. J. Biol. Chem. 270: 2158-2162.

Kandasamy RA, Yu FH, Harris RA, Boucher A, Hanrahan JW and Orlowski J. 1995. Plasma membrane Na/H exchanger isoforms (NHE-1,-2,-3) are differentially responsive to second messenger agonists of the protein kinase A and C pathways.  J. Biol. Chem. 270: 29209-29216.

Reddy MM, Quinton PM, Haws C, Wine JJ, Grygorczyk R, Tabcharani JA, Hanrahan JW, Gunderson KL and Kopito RR 1996. Failure of the cystic fibrosis transmembrane conductance regulator to conduct ATP.  Science 271: 1876-1879.

Becq F, Verrier B, Chang X-B, Riordan JR and Hanrahan JW 1996. cAMP- and Ca2+-independent activation of CFTR channels by phenylimidazothiazole drugs.  J. Biol. Chem. 271:16171-16179.

Seibert FS, Linsdell P, Loo TW, Hanrahan JW, Clarke DM and Riordan JR 1996.  Disease-causing mutations in the fourth cytoplasmic loop of CFTR compromise biosynthetic processing and chloride channel activity.  J. Biol. Chem. 271: 15139-15145.

Seibert FS, Linsdell P, Loo TW, Hanrahan JW, Riordan JR and Clarke DM 1996.  Cytoplasmic loop three of CFTR contributes to regulation of chloride channel activity. J. Biol. Chem. 271: 27493-27499.

Jia Y, Mathews CJ and Hanrahan JW 1997.  Phosphorylation by protein kinase C (PKC) is required for acute activation of CFTR by protein kinase A (PKA). J. Biol. Chem. 272: 4978-4984.

Grygorczyk R. and Hanrahan JW  1997.  CFTR-independent release of ATP from epithelial cells triggered by mechanical stimuli. Am. J. Physiol. (Cell Physiol.) 272: C1058-C1066.

Linsdell P, Tabcharani JA and Hanrahan JW 1997.  Multi-ion mechanism for ion permeation and block in the cystic fibrosis transmembrane conductance regulator chloride channel. J. Gen. Physiol. 110: 365-377.

Linsdell P, Tabcharani JA, Rommens JM, Hou Y-X, Chang X-B, Tsui L-C, Riordan JR and Hanrahan JW 1997.  Permeability of wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels to polyatomic anions. J. Gen. Physiol. 110: 355-364.

Tabcharani JA, Linsdell P and Hanrahan JW 1997.  Halide permeation in wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels. J. Gen. Physiol.  110: 431-354.

Seibert FS, Jia Y, Loo TW, Mathews CJ, Hanrahan JW, Riordan JR and Clarke DM 1997.  Disease-associated mutations in cytoplasmic loops one and two of CFTR impede processing or opening of the channel. Biochemistry  36: 11966-11974.

Mathews CJ, Tabcharani JA, Chang X-B, Jensen, TJ, Riordan JR and Hanrahan JW 1998.  Dibasic protein kinase A sites regulate bursting rate and nucleotide sensitivity of the cystic fibrosis transmembrane conductance regulator chloride channel. J.Physiol. 508: 365-377.

Luo J, Pato MD, Seibert FS, Riordan JR and Hanrahan JW 1998. Differential regulation of single CFTR channels by PP2C, PP2A and other phosphatases.  Am. J. Physiol. Cell Physiol. 274: 1397-1410.

Linsdell P and Hanrahan JW 1998.  Adenosine triphosphate-dependent asymmetry of anion permeation in the cystic fibrosis transmembrane conductance regulator chloride channel. J. Gen. Physiol. 111: 601-614.

Linsdell P, Zheng S-X and Hanrahan JW 1998.  Non-pore lining amino acid side chains influence anion selectivity of the human CFTR Cl- channel expressed in mammalian cell lines. J. Physiol. 512:1-16.

Zhu T, Dahan D, Evagelidis A, Zheng S-X, Luo J and Hanrahan JW  1999.  Association of cystic fibrosis transmembrane conductance regulator and protein phosphatase 2C.  J. Biol. Chem. 274:29102-29107.

Linsdell P, Evagelidis A and Hanrahan JW 2000.  Molecular determinants of anion selectivity in the cystic fibrosis transmembrane conductance regulator chloride channel pore. Biophys. J. 78:2973-2982.

Luo J, Zhu T, Evagelidis A, Pato MD and Hanrahan JW 2000.  Role of protein phosphatases in the activation of CFTR (ABCC7) by genistein and p-bromotetramisole.  Am. J. Physiol. Cell Physiol. 279:C108-C119.

Gupta J, Evagelidis A, Hanrahan JW and Linsdell P 2001.  Asymmetric structure of the cystic fibrosis transmembrane conductance regulator chloride channel pore suggested by mutagenesis of the twelfth transmembrane region.  Biochemistry  40:6620-6627.

Guyot A and Hanrahan JW 2002.  Release of ATP from epithelial cells studied using a capillary cell culture system. J. Physiol. 545:199-206.

Naren AP, Cobb B, Li C, Roy K, Nelson D, Heda GD, Liao J, Kirk KL, Sorscher E, Hanrahan JW and Clancy JP 2003.  Coupling receptors to channels: A macromolecular complex of b2AR, CFTR and EBP50 is regulated by protein kinase A.  Proc Natl. Acad. Sci. (USA) 100:342-346.

Chappe V, Hinkson DA, Zhu T, Chang X-B, Riordan JR and Hanrahan JW 2003.  Phosphorylation of protein kinase C sites in NBD1 and the R domain control CFTR channel activation by PKA. J. Physiol. 548:39-52.

Chappe V, Hinkson DA, Howell LD, Evagelidis A, Liao J, Chang X-B, Riordan JR and Hanrahan JW 2004.  Stimulatory and inhibitory PKC consensus sequences regulate CFTR.  Proc. Natl Acad. Sci (USA) 101:390-395.

 

C. CURRENT RESEARCH SUPPORT
 

2 RO1 DK054075-05A1          Hanrahan (PI)              7/01/02 – 6/30/05        NIH/NIDDK                 
Phosphatase regulation of CFTR
This project is to identify the protein phosphatase that regulates CFTR and characterize its dephosphorylation.
Role: PI

Operating grant                       Hanrahan (PI)              4/1/01 – 3/31/04         
Canadian Cystic Fibrosis Foundation                                   
CFTR in cell regulation
This project is to examine regulation of CFTR channels by PKC and other kinases, and determine its interactions with scaffolding proteins. 
Role: PI

MT-12548                                Hanrahan (PI)              10/1/02 – 9/30/07       
Canadian Institutes of Health Research                                
Epithelial chloride channels
This project is to understand biophysical aspects of permeation in the CFTR pore, and the relationship between structure and function in the nucleotide binding domains.  
Role: PI

1 R21 DK066644-01               Hanrahan (PI)              01/01/04 – 12/31/06   
NIH/NIDDK                 
Release of epithelially-derived factors in interstitial cystitis
This project is to study the release of ATP from urinary bladder epithelial cells in vitro and in a model of interstitial cystitis.
Role: PI

BREATHE/RESPIRE Program               Hanrahan (PI)              04/01/04 – 03/31/07   
Canadian Cystic Fibrosis Foundation/Canadian Institutes of Health Research (CIHR)
Institute of Circulatory and Respiratory Health (ICRH) and Institute of Infection and Immunity (III)
Innovative Targets for CF Therapy
This program includes 8 investigators at three institutions (McGill University, Université de Montréal, and Université de Sherbrooke). The goal is to identify and develop potential targets for cystic fibrosis therapies.
Role: Program Director and Principal Investigator

This page was last edited on 18 August, 2004