Seth Alper

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Transcriptional patterns in peritoneal tissue of encapsulating peritoneal sclerosis, a complication of chronic peritoneal dialysis
    Fabian R Reimold
    Renal Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 8:e56389. 2013
  2. pmc Hypoxia activates a Ca2+-permeable cation conductance sensitive to carbon monoxide and to GsMTx-4 in human and mouse sickle erythrocytes
    David H Vandorpe
    Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:e8732. 2010
  3. pmc The SLC26 gene family of anion transporters and channels
    Seth L Alper
    Renal Division and Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Mol Aspects Med 34:494-515. 2013
  4. ncbi Molecular physiology of SLC4 anion exchangers
    Seth L Alper
    Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Exp Physiol 91:153-61. 2006
  5. pmc Reduced DIDS-sensitive chloride conductance in Ae1-/- mouse erythrocytes
    Seth L Alper
    Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Blood Cells Mol Dis 41:22-34. 2008
  6. ncbi Let's look at cysts from both sides now
    Seth L Alper
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    Kidney Int 74:699-702. 2008
  7. pmc Molecular physiology and genetics of Na+-independent SLC4 anion exchangers
    Seth L Alper
    Renal Division and Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Exp Biol 212:1672-83. 2009
  8. ncbi Familial renal tubular acidosis
    Seth L Alper
    Renal Division and Molecular and Vascular Medicine Division, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Nephrol 23:S57-76. 2010
  9. pmc Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG F65S
    Andrew K Stewart
    Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Cell Physiol 301:C1325-43. 2011
  10. ncbi Transmembrane domain histidines contribute to regulation of AE2-mediated anion exchange by pH
    A K Stewart
    Beth Israel Deaconess Medical Center, 330 Brookline Ave, E RW763, Boston, MA 02215, USA
    Am J Physiol Cell Physiol 292:C909-18. 2007

Collaborators

Detail Information

Publications82

  1. pmc Transcriptional patterns in peritoneal tissue of encapsulating peritoneal sclerosis, a complication of chronic peritoneal dialysis
    Fabian R Reimold
    Renal Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 8:e56389. 2013
    ..The results are compatible with the hypothesis that encapsulating peritoneal sclerosis is a distinct pathological process from the simple peritoneal fibrosis that accompanies all PD treatment...
  2. pmc Hypoxia activates a Ca2+-permeable cation conductance sensitive to carbon monoxide and to GsMTx-4 in human and mouse sickle erythrocytes
    David H Vandorpe
    Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:e8732. 2010
    ..Deoxygenation-induced currents sharing some properties of Psickle have been recorded from sickle erythrocytes in whole cell configuration...
  3. pmc The SLC26 gene family of anion transporters and channels
    Seth L Alper
    Renal Division and Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Mol Aspects Med 34:494-515. 2013
    ..The protein interactomes of SLC26 polypeptides are under active investigation...
  4. ncbi Molecular physiology of SLC4 anion exchangers
    Seth L Alper
    Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Exp Physiol 91:153-61. 2006
    ..This growing body of structure-function data, together with increased structural information, will advance mechanistic understanding of SLC4 anion exchangers...
  5. pmc Reduced DIDS-sensitive chloride conductance in Ae1-/- mouse erythrocytes
    Seth L Alper
    Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Blood Cells Mol Dis 41:22-34. 2008
    ..Thus, loss of one or more distinct, DIDS-sensitive anion channel polypeptide(s) from the Ae1(-/-) red cell membrane cannot be ruled out as an explanation for the reduced DIDS-sensitive anion conductance...
  6. ncbi Let's look at cysts from both sides now
    Seth L Alper
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    Kidney Int 74:699-702. 2008
    ..1 K(+) channel, using a nontoxic small molecule with a close congener poised for rapid entry into the clinic. Cyst fluid accumulation can be blocked from both sides now...
  7. pmc Molecular physiology and genetics of Na+-independent SLC4 anion exchangers
    Seth L Alper
    Renal Division and Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Exp Biol 212:1672-83. 2009
    ..A growing body of structure-function and interaction data, together with emerging information about physiological function and structure, is advancing our understanding of SLC4 anion exchangers...
  8. ncbi Familial renal tubular acidosis
    Seth L Alper
    Renal Division and Molecular and Vascular Medicine Division, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Nephrol 23:S57-76. 2010
    ..Additional RTA genes identified in knockout mice may lead to identification of additional human RTA genes...
  9. pmc Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG F65S
    Andrew K Stewart
    Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Cell Physiol 301:C1325-43. 2011
    ..Thus, RhAG F65S is a loss-of-function mutation for amine transport. The altered oocyte intracellular pH, membrane potential, and currents associated with RhAG or RhAG F65S expression may reflect distinct transport mechanisms...
  10. ncbi Transmembrane domain histidines contribute to regulation of AE2-mediated anion exchange by pH
    A K Stewart
    Beth Israel Deaconess Medical Center, 330 Brookline Ave, E RW763, Boston, MA 02215, USA
    Am J Physiol Cell Physiol 292:C909-18. 2007
    ..The results show that multiple TMD His residues contribute to basal AE2 activity and its sensitivity to pH(i) and pH(o)...
  11. pmc Regulation of AE2-mediated Cl- transport by intracellular or by extracellular pH requires highly conserved amino acid residues of the AE2 NH2-terminal cytoplasmic domain
    A K Stewart
    Department of Medicine, Harvard Medical School, Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Gen Physiol 120:707-22. 2002
    ..Conserved, individual amino acid residues of the AE2 cytoplasmic domain contribute to independent regulation of anion exchange activity by pH(o) as well as pH(i)...
  12. ncbi Regulation of AE2 anion exchanger by intracellular pH: critical regions of the NH(2)-terminal cytoplasmic domain
    A K Stewart
    Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston 02215, USA
    Am J Physiol Cell Physiol 281:C1344-54. 2001
    ..Our data define structure-function relationships within the AE2 NH(2)-terminal cytoplasmic domain, which demonstrates distinct structural requirements for AE2 regulation by intracellular and extracellular protons...
  13. ncbi Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation
    W Su
    Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston 02215, USA
    Am J Physiol 277:C899-912. 1999
    ..These reagents and findings will expedite studies of KCC1 structure-function relationships and of the pathobiology of KCC1-mediated K-Cl cotransport...
  14. pmc Acute regulation of mouse AE2 anion exchanger requires isoform-specific amino acid residues from most of the transmembrane domain
    A K Stewart
    Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Physiol 584:59-73. 2007
    ....
  15. pmc Functional coupling of apical Cl-/HCO3- exchange with CFTR in stimulated HCO3- secretion by guinea pig interlobular pancreatic duct
    A K Stewart
    Renal Division, Molecular and Vascular Medicine Unit, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Gastrointest Liver Physiol 296:G1307-17. 2009
    ..This study demonstrates functional coupling between Cftr and Slc26a6-like Cl(-)/HCO(3)(-) exchange activity in apical membrane of guinea pig pancreatic interlobular duct...
  16. ncbi Proteolytic cleavage sites of native AE2 anion exchanger in gastric mucosal membranes
    A S Zolotarev
    Molecular Medicine Unit, Beth Israel Hospital, Boston, Massachusetts 02215, USA
    Biochemistry 35:10367-76. 1996
    ..These results provide experimental confirmation for some aspects of AE2 topography previously predicted from primary structure alone...
  17. ncbi VHL tumor suppressor regulates Cl-/HCO3- exchange and Na+/H+ exchange activities in renal carcinoma cells
    S A Karumanchi
    Renal Division, Beth Israel Deaconess Medical Center, Departments of Medicine and Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, USA
    Physiol Genomics 5:119-28. 2001
    ..AE2 and NHE3 are the first transcripts reported to be upregulated by pVHL. Elucidation of mechanisms responsible for downregulation of both ion exchange activities will require further investigation...
  18. ncbi AE anion exchangers in atrial tumor cells
    P Papageorgiou
    Harvard-Thorndike Institute of Electrophysiology, Cardiovascular Division, Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Am J Physiol Heart Circ Physiol 280:H937-45. 2001
    ..Both bAE3 and cAE3 were present in intact AT-1 tumors. Cultured AT-1 cells provide a useful system for the study of mediators and regulators of Cl(-)/HCO(3)(-) exchange activity in an atrial cell type...
  19. ncbi Role of nonconserved charged residues of the AE2 transmembrane domain in regulation of anion exchange by pH
    A K Stewart
    Molecular and Vascular Medicine Unit and Renal Unit, Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Pflugers Arch 454:373-84. 2007
    ....
  20. ncbi Mannitol at clinical concentrations activates multiple signaling pathways and induces apoptosis in endothelial cells
    A M Malek
    Department of Neurosurgery, Brigham and Women s Hospital, Children s Hospital, and Harvard Medical School, Boston, Mass, USA
    Stroke 29:2631-40. 1998
    ..Though beneficial rheological effects commonly are attributed to mannitol, its direct effects on endothelial cells are poorly understood...
  21. ncbi Regulation of Na+-independent Cl-/HCO3- exchangers by pH
    S L Alper
    Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    JOP 2:171-5. 2001
    ..Little is known about the acute regulation of these modulators of intracellular and compartmental pH and volume...
  22. ncbi Intracellular Ca(2+) signaling in endothelial cells by the angiogenesis inhibitors endostatin and angiostatin
    L Jiang
    Molecular Medicine and Renal Units and The Cancer Center, Beth Israel Deaconess Medical Center and Departments of Medicine and Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, USA
    Am J Physiol Cell Physiol 280:C1140-50. 2001
    ..Intracellular Ca(2+) signaling may initiate or mediate some of the cellular actions of endostatin and angiostatin...
  23. ncbi Hemodynamic shear stress and its role in atherosclerosis
    A M Malek
    Neurosurgery, Brigham and Women s Hospital and Children s Hospital, Boston, Mass 02115, USA
    JAMA 282:2035-42. 1999
    ....
  24. ncbi Expression of AE2 anion exchanger in mouse intestine
    S L Alper
    Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Am J Physiol 277:G321-32. 1999
    ..These localization studies will aid in the interpretation of anion exchanger function measured in epithelial sheets, isolated cells, and membrane vesicles...
  25. ncbi Endothelin-1 gene suppression by shear stress: pharmacological evaluation of the role of tyrosine kinase, intracellular calcium, cytoskeleton, and mechanosensitive channels
    A M Malek
    Department of Neurosurgery, Brigham and Women s Hospital, Children s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Mol Cell Cardiol 31:387-99. 1999
    ....
  26. pmc The antifungal antibiotic, clotrimazole, inhibits Cl- secretion by polarized monolayers of human colonic epithelial cells
    P A Rufo
    Combined Program in Pediatric Gastroenterology and Nutrition, Children s Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 98:2066-75. 1996
    ..CLT acts distal to the generation of cAMP and Ca2+ signals, and appears to inhibit basolateral K+ channels directly. CLT and related drugs may serve as novel antidiarrheal agents in humans and animals...
  27. ncbi cDNA cloning and functional characterization of the mouse Ca2+-gated K+ channel, mIK1. Roles in regulatory volume decrease and erythroid differentiation
    D H Vandorpe
    Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center Boston, Massachusetts 02215, USA
    J Biol Chem 273:21542-53. 1998
    ..Low nanomolar concentrations of CLT inhibited proliferation and erythroid differentiation of peripheral blood stem cells in liquid culture...
  28. ncbi Immunolocalization and tissue-specific splicing of AE2 anion exchanger in mouse kidney
    A K Stuart-Tilley
    Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Am Soc Nephrol 9:946-59. 1998
    ..Unlike in rat, the mouse AE2c2 mRNA splice variant encoded a polypeptide with a novel predicted N-terminal amino acid sequence...
  29. pmc The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K+ conductances. Demonstration of efficacy in intact rabbit colon and in an in vivo mouse model of cholera
    P A Rufo
    Combined Program in Pediatric Gastroenterology and Nutrition, Children s Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 100:3111-20. 1997
    ..The results further support the suggestion that CLT and its metabolites may show clinical efficacy in the treatment of secretory diarrheas of diverse etiologies...
  30. pmc Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease
    C Brugnara
    Department of Laboratory Medicine, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 97:1227-34. 1996
    ..This is the first in vivo evidence that the Gardos channel causes dehydration of sickle erythrocytes, and that its pharmacologic inhibition provides a realistic antisickling strategy...
  31. ncbi AE2 anion exchanger polypeptide is a homooligomer in pig gastric membranes: a chemical cross-linking study
    A S Zolotarev
    Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Biochemistry 38:8521-31. 1999
    ..AE2 cross-linking could not be detected in membranes pretreated by hypotonic wash and freeze-thaw. The results are interpreted in light of the deduced amino acid sequence of the transmembrane domain of pig AE2...
  32. ncbi Molecular cloning, expression, and chromosomal localization of two isoforms of the AE3 anion exchanger from human heart
    D Yannoukakos
    Molecular Medicine Unit, Beth Israel Hospital, Boston, MA 02215
    Circ Res 75:603-14. 1994
    ..The human AE3 gene was localized to chromosome 2. AE3 may provide a new pharmacologic target for antiarrhythmic and cardioprotective drugs...
  33. ncbi Structure and complex transcription pattern of the mouse SK1 K(Ca) channel gene, KCNN1
    B E Shmukler
    Molecular Medicine Unit, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
    Biochim Biophys Acta 1518:36-46. 2001
    ..The evolutionary conservation of this complex transcription pattern suggests a possible role in the tuning of SK1 channel function...
  34. ncbi A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity
    S Casula
    Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Biol Chem 276:41870-8. 2001
    ..Delta(N)117 also exhibited dominant negative inhibition of human KCC1 and KCC3 and, with lower potency, mouse KCC4 and rat KCC2...
  35. ncbi The band 3-related anion exchanger (AE) gene family
    S L Alper
    Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts
    Annu Rev Physiol 53:549-64. 1991
  36. ncbi Structure and genetic polymorphism of the mouse KCC1 gene
    B E Shmukler
    Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Biochim Biophys Acta 1492:353-61. 2000
    ..These and additional described strain-specific polymorphisms will be useful mapping and genetic tools in the study of mouse models of sickle cell disease...
  37. ncbi The cytoplasmic C-terminal fragment of polycystin-1 regulates a Ca2+-permeable cation channel
    D H Vandorpe
    Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 276:4093-101. 2001
    ..Dysregulation of these or similar channels in autosomal dominant polycystic kidney disease may contribute to cyst formation or expansion...
  38. pmc SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization
    Andrew K Stewart
    Renal Division and Vascular Biology Center, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Am J Physiol Cell Physiol 301:C289-303. 2011
    ..This first molecular and functional assessment of recombinant SLC26 anion transporters from guinea pig pancreatic duct enhances our understanding of pancreatic HCO(3)(-) secretion in species that share a high HCO(3)(-) secretory output...
  39. pmc Functional characterization and modified rescue of novel AE1 mutation R730C associated with overhydrated cation leak stomatocytosis
    Andrew K Stewart
    Division of Nephrology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Cell Physiol 300:C1034-46. 2011
    ..Selective rescue of acid pH(o)-stimulated sulfate uptake and conferral of acid pH(o)-stimulated Cl(-) influx, by AE1 R730E and MTSES-treated R730C, define residue R730 as critical to selectivity and regulation of anion transport by AE1...
  40. ncbi Chromosomal mapping of the rat Slc4a family of anion exchanger genes, Ae1, Ae2, and Ae3
    J S Simon
    Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, 02129, USA
    Mamm Genome 7:380-2. 1996
  41. pmc Regulated transport of sulfate and oxalate by SLC26A2/DTDST
    John F Heneghan
    Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Am J Physiol Cell Physiol 298:C1363-75. 2010
    ..Diastrophic dysplasia mutants R279W and A386V of hSLC26A2 exhibited similar reductions in uptake of both (35)SO(4)(2-) and [(14)C]oxalate. A386V surface abundance was reduced, but R279W surface abundance was at wild-type levels...
  42. pmc The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes
    Andrew K Stewart
    Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Am J Physiol Cell Physiol 298:C283-97. 2010
    ....
  43. ncbi Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse
    Amjad Kanaan
    Department of Pediatrics, Section of Respiratory Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Am J Physiol Regul Integr Comp Physiol 293:R1294-302. 2007
    ....
  44. ncbi Interactions of transmembrane carbonic anhydrase, CAIX, with bicarbonate transporters
    Patricio E Morgan
    Membrane Protein Research Group, Dept of Physiology, University of Alberta, Edmonton, Alberta, Canada
    Am J Physiol Cell Physiol 293:C738-48. 2007
    ..We conclude that CAIX can bind to some Cl(-)/HCO(3)(-) exchangers to form a bicarbonate transport metabolon...
  45. ncbi Distal renal tubular acidosis in mice lacking the AE1 (band3) Cl-/HCO3- exchanger (slc4a1)
    Paul A Stehberger
    Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
    J Am Soc Nephrol 18:1408-18. 2007
    ....
  46. ncbi Enhanced suicidal death of erythrocytes from gene-targeted mice lacking the Cl-/HCO(3)(-) exchanger AE1
    Ahmad Akel
    Department of Physiology, University of Tubingen, Tubingen, Germany
    Am J Physiol Cell Physiol 292:C1759-67. 2007
    ..In conclusion, lack of AE1 is associated with enhanced Ca(2+) entry and subsequent scrambling of cell membrane phospholipids...
  47. ncbi Diarrhea-associated HIV-1 APIs potentiate muscarinic activation of Cl- secretion by T84 cells via prolongation of cytosolic Ca2+ signaling
    Paul A Rufo
    GI Cell Biology, Combined Program in Pediatric Gastroenterology and Nutrition, Children s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
    Am J Physiol Cell Physiol 286:C998-C1008. 2004
    ..These data show that APIs modulate Ca(2+) signaling in secretory epithelial cells and identify a novel target for treatment of clinically important API side effects...
  48. ncbi Enhanced formation of a HCO3- transport metabolon in exocrine cells of Nhe1-/- mice
    Mireya Gonzalez-Begne
    Center for Oral Biology, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 282:35125-32. 2007
    ....
  49. ncbi Zebrafish ae2.2 encodes a second slc4a2 anion exchanger
    Boris E Shmukler
    Molecular and Vascular Medicine and Renal Units, Beth Israel Deaconess Medical Center E RW763, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Regul Integr Comp Physiol 294:R1081-91. 2008
    ..1 mRNA, or of both with nontoxic or minimally toxic levels of N-morpholino oligomers produced no grossly detectable morphological phenotype, and preserved normal structure of the head and the pronephric duct at 24 h postfertilization...
  50. pmc Species differences in Cl- affinity and in electrogenicity of SLC26A6-mediated oxalate/Cl- exchange correlate with the distinct human and mouse susceptibilities to nephrolithiasis
    Jeffrey S Clark
    Molecular and Vascular Medicine Unit and Renal Division, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    J Physiol 586:1291-306. 2008
    ..SLC26A6 sequence variant(s) are candidate risk modifiers for nephrolithiasis...
  51. doi Mouse strain-specific coding polymorphism in the Slc4a2/Ae2 gene encodes Ae2c2 variants differing in isoform-specific dominant negative activity
    Christine E Kurschat
    Molecular and Vascular Medicine and Renal Units, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
    Exp Physiol 93:458-67. 2008
    ..Knowledge of strain-specific coding polymorphisms with potential functional consequences such as that of Ae2c2 should aid in interpretation of strain-specific phenotypes investigated in the mouse phenome project...
  52. pmc Increased sulfate uptake by E. coli overexpressing the SLC26-related SulP protein Rv1739c from Mycobacterium tuberculosis
    Alexander S Zolotarev
    Molecular and Vascular Medicine and Renal Divisions, Beth Israel Deaconess Medical Center, USA
    Comp Biochem Physiol A Mol Integr Physiol 149:255-66. 2008
    ..Our data show that facilitation of bacterial sulfate uptake by Rv1739c requires CysA and its associated sulfate permease activity, and suggest that Rv1739c may be a CysTWA-dependent sulfate transporter...
  53. pmc Mouse Ae1 E699Q mediates SO42-i/anion-o exchange with [SO42-]i-dependent reversal of wild-type pHo sensitivity
    Marina N Chernova
    Molecular and Vascular Medicine Unit, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Cell Physiol 295:C302-12. 2008
    ....
  54. ncbi Anion exchangers in flux: functional differences between human and mouse SLC26A6 polypeptides
    Seth L Alper
    Molecular and Vascular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Novartis Found Symp 273:107-19; discussion 119-25, 261-4. 2006
    ..Understanding of SLC26 transport mechanisms and pathophysiology will benefit from recognition of substantial differences in transport properties among orthologues...
  55. ncbi Genetic diseases of acid-base transporters
    Seth L Alper
    Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Department of Medicine and Cell Biology, Harvard Medical School Boston, Massachusetts 02215, USA
    Annu Rev Physiol 64:899-923. 2002
    ..Study of acid-base transport disease-associated mutations should enhance our understanding of protein structure-function relationships and their impact on the physiology of cell, tissue, and organism...
  56. ncbi Defects in processing and trafficking of the AE1 Cl-/HCO3- exchanger associated with inherited distal renal tubular acidosis
    Chairat Shayakul
    Renal Unit, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
    Clin Exp Nephrol 8:1-11. 2004
    ....
  57. ncbi Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis
    Chairat Shayakul
    Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Nephrol Dial Transplant 19:371-9. 2004
    ..Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation...
  58. ncbi Cl(-)/HCO(3)(-) exchange is acetazolamide sensitive and activated by a muscarinic receptor-induced [Ca(2+)](i) increase in salivary acinar cells
    Ha Van Nguyen
    Center for Oral Biology, University of Rochester Medical Center, Rochester, New York 14642, USA
    Am J Physiol Gastrointest Liver Physiol 286:G312-20. 2004
    ..Moreover, muscarinic receptor stimulation enhanced AE activity through a Ca(2+)-dependent mechanism. Such forms of regulation may play important roles in modulating fluid and electrolyte secretion by salivary gland acinar cells...
  59. ncbi Deficient HCO3- transport in an AE1 mutant with normal Cl- transport can be rescued by carbonic anhydrase II presented on an adjacent AE1 protomer
    Neera K Dahl
    Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 278:44949-58. 2003
    ..The data strongly support the hypothesis that an intact transbilayer anion translocation pathway is completely contained within an AE1 monomer...
  60. ncbi Identification of a basolateral Cl-/HCO3- exchanger specific to gastric parietal cells
    Snezana Petrovic
    Department of Medicine, University of Cincinnati, Cincinnati 45267, USA
    Am J Physiol Gastrointest Liver Physiol 284:G1093-103. 2003
    ..On the basis of its unique expression pattern and function, we propose that SLC26A7 is a basolateral Cl(-)/HCO(3)(-) exchanger in gastric parietal cells and plays a major role in gastric acid secretion...
  61. pmc Acute regulation of the SLC26A3 congenital chloride diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes
    Marina N Chernova
    Molecular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Physiol 549:3-19. 2003
    ..Thus, pharmacological modulation of DRA might be a useful adjunct treatment of cystic fibrosis...
  62. ncbi Structure-function relationships of AE2 regulation by Ca(i)(2+)-sensitive stimulators NH(4+) and hypertonicity
    Marina N Chernova
    Molecular Medicine and Renal Units, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Am J Physiol Cell Physiol 284:C1235-46. 2003
    ..AE2 was insensitive to many other modifiers of Ca(2+) signaling. Unlike AE2 stimulation by NH(4)(+) and by hypertonicity, AE2 inhibition by calmidazolium required only AE2's COOH-terminal transmembrane domain...
  63. ncbi How pH regulates a pH regulator: a regulatory hot spot in the N-terminal cytoplasmic domain of the AE2 anion exchanger
    Seth L Alper
    Department of Medicine, Harvard Medical School, Boston, MA, USA
    Cell Biochem Biophys 36:123-36. 2002
    ..Noncontiguous regions in the middle of the N-terminal cytoplasmic domain are of particular importance for acute regulation by several types of stimulus...
  64. ncbi The AE gene family of Cl/HCO3- exchangers
    Seth L Alper
    Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Nephrol 15:S41-53. 2002
    ..Noncontiguous regions in the middle of the N-terminal cytoplasmic domain are of particular importance for acute regulation by several types of stimulus...
  65. ncbi Cation channel regulation by COOH-terminal cytoplasmic tail of polycystin-1: mutational and functional analysis
    David H Vandorpe
    Molecular Medicine, Beth Israel Deaconess Medical Center, Boston 02215, USA
    Physiol Genomics 8:87-98. 2002
    ..The divalent cation permeability and pharmacological profile of the current has been extended. Inducible expression of the PKD1 fusion in EcR-293 cells was also associated with activation of cation channels and increased Ca2+ entry...
  66. ncbi Mice with a targeted disruption of the AE2 Cl-/HCO3- exchanger are achlorhydric
    Lara R Gawenis
    Department of Molecular Genetics, Biochemistry and Microbiology, Unniversity of Cincinnati College of Medicine, Ohio 45267, USA
    J Biol Chem 279:30531-9. 2004
    ..These results demonstrate that AE2 is essential for gastric acid secretion and for normal development of secretory canalicular and tubulovesicular membranes in mouse parietal cells...
  67. ncbi Apparent receptor-mediated activation of Ca2+-dependent conductive Cl- transport by shark-derived polyaminosterols
    Marina N Chernova
    Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Am J Physiol Regul Integr Comp Physiol 289:R1644-58. 2005
    ....
  68. ncbi Acute pH-dependent regulation of AE2-mediated anion exchange involves discrete local surfaces of the NH2-terminal cytoplasmic domain
    Andrew K Stewart
    Burdon Sanderson Cardiac Science Centre, University Laboratory of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom
    J Biol Chem 279:52664-76. 2004
    ....
  69. ncbi Functional comparison of mouse slc26a6 anion exchanger with human SLC26A6 polypeptide variants: differences in anion selectivity, regulation, and electrogenicity
    Marina N Chernova
    Molecular and Vascular Medicine Unit and Renal Unit, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 280:8564-80. 2005
    ..Thus, the orthologous mouse and human SLC26A6 proteins differ in anion selectivity, transport mechanism, and acute regulation, but both mediate electroneutral Cl(-)/HCO(3)(-) exchange...
  70. ncbi Regulation of the Cl-/HCO3- exchanger AE2 in rat thick ascending limb of Henle's loop in response to changes in acid-base and sodium balance
    Fabienne Quentin
    Unité INSERM 356, Institut de Recherche des Cordeliers, 15 rue de l Ecole de Medecine, 75270 Paris Cedex 06, France
    J Am Soc Nephrol 15:2988-97. 2004
    ..The present study also emphasizes the contribution of cortical TAL adaptation in the renal regulation of acid-base status...
  71. ncbi Alkaline-shifted pHo sensitivity of AE2c1-mediated anion exchange reveals novel regulatory determinants in the AE2 N-terminal cytoplasmic domain
    Christine E Kurschat
    Molecular and Vascular Medicine and Renal Units, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
    J Biol Chem 281:1885-96. 2006
    ..Physiological coexpression of AE2c1 with other AE2 variant polypeptides in the same cell should extend the range over which changing pH(o) can regulate AE2 transport activity...
  72. ncbi Expression of the polycystin-1 C-terminal cytoplasmic tail increases Cl channel activity in Xenopus oocytes
    Marina N Chernova
    Molecular and Vascular Medicine Unit and Renal Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    Kidney Int 68:632-41. 2005
    ..Conclusion. These data show that CD16.7-PKD1 (115-226) activates Cl(-) channels in the Xenopus oocyte plasma membrane in parallel with, but not secondary to, activation of Ca(2+)-permeable cation channels...
  73. ncbi Zebrafish slc4a2/ae2 anion exchanger: cDNA cloning, mapping, functional characterization, and localization
    Boris E Shmukler
    Molecular Medicine and Renal Units, Beth Israel Deaconess Med Ctr E RW763, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Renal Physiol 289:F835-49. 2005
    ..These results will inform tests of the role of Ae2 in zebrafish kidney development and function...
  74. pmc Cellular actions and signaling by endostatin
    Ramani Ramchandran
    Division of Nephrology, Department of Medicine and Center for Study of the Tumor Microenvironment, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Crit Rev Eukaryot Gene Expr 12:175-91. 2002
    ..This review summarizes recent advances in endostatin biology and highlights new results on the cellular and subcellular mechanisms of endostatin action...
  75. ncbi Immunolocalization of potassium-chloride cotransporter polypeptides in rat exocrine glands
    Eleni Roussa
    Department of Neuroanatomy, Georg August University, Gottingen, Germany
    Histochem Cell Biol 117:335-44. 2002
    ..These results establish the presence in rat exocrine glands of KCC1 and likely other KCC polypeptides, and suggest a contribution of KCC polypeptides to transepithelial Cl(-) transport...
  76. ncbi Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4
    Ted Begenisich
    Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:47681-7. 2004
    ..Surprisingly, Kcnn4 channels appear to play no required role in fluid secretion and regulatory volume decrease in the parotid gland...
  77. pmc Disruption of erythroid K-Cl cotransporters alters erythrocyte volume and partially rescues erythrocyte dehydration in SAD mice
    Marco B Rust
    Zentrum fur Molekulare Neurobiologie Hamburg, Universitat Hamburg, Hamburg, Germany
    J Clin Invest 117:1708-17. 2007
    ..Although disruption of K-Cl cotransport rescued the dehydration phenotype of most SAD rbc, the proportion of the densest red blood cell population remained unaffected...
  78. ncbi Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency
    Barry H Paw
    Department of Medicine, Division of Hematology Oncology, Children s Hospital, Boston, Massachusetts, USA
    Nat Genet 34:59-64. 2003
    ..1R-binding domains. Our report establishes an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrates the concept of cell-specific adaptation for mitosis...
  79. ncbi KCl cotransport is an important modulator of human cervical cancer growth and invasion
    Meng Ru Shen
    Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
    J Biol Chem 278:39941-50. 2003
    ..Thus, blockade of KCl cotransport may be a useful therapeutic adjunctive strategy to retard or prevent cervical cancer invasion...
  80. ncbi The abts and sulp families of anion transporters from Caenorhabditis elegans
    Teresa Sherman
    Department of Medicine Nephrology Unit, University of Rochester Medical Center, Rochester, New York 14642, USA
    Am J Physiol Cell Physiol 289:C341-51. 2005
    ..These findings encourage exploitation of the genetic strengths of the nematode model system in the study of the physiological roles of anion transport by the proteins of these two highly conserved gene families...
  81. pmc Human ADPKD primary cyst epithelial cells with a novel, single codon deletion in the PKD1 gene exhibit defective ciliary polycystin localization and loss of flow-induced Ca2+ signaling
    Chang Xu
    Molecular and Vascular Medicine Unit and Renal Division, Beth Israel Deaconess Medical Center E RW763, Boston, MA 02215, USA
    Am J Physiol Renal Physiol 292:F930-45. 2007
    ..7-PKD1(115-226) expression to accelerate decay of the flow-induced Ca(2+) signal in NK cells. These data provide evidence for ciliary dysfunction and polycystin mislocalization in human ADPKD cells with normal levels of PC1...

Research Grants12

  1. ION CHANNEL REGULATION BY THE CYTOPLASMIC TAIL OF PDK1
    Seth Alper; Fiscal Year: 2002
    ..We will search for novel interacting proteins, and prepare protein suitable for structural analysis. ..
  2. RBC Ion Transporters as Hemoglobinopathy Risk Modifiers
    Seth Alper; Fiscal Year: 2009
    ..The proposed experiments will increase understanding of sickle cell disease and thalassemia by providing mouse models for genetic tests of new drug therapies under development for near-term clinical testing. ..
  3. RBC Ion Transporters as Hemoglobinopathy Risk Modifiers
    Seth Alper; Fiscal Year: 2007
    ..The proposed experiments will increase understanding of sickle cell disease and thalassemia by providing mouse models for genetic tests of new drug therapies under development for near-term clinical testing. ..
  4. RBC Ion Transporters as Hemoglobinopathy Risk Modifiers
    Seth Alper; Fiscal Year: 2007
    ..The proposed experiments will increase understanding of sickle cell disease and thalassemia by providing mouse models for genetic tests of new drug therapies under development for near-term clinical testing. ..
  5. MOLECULAR PHYSIOLOGY OF BAND 3 LIKE PROTEINS OF KIDNEY
    Seth Alper; Fiscal Year: 2007
    ..5. Define aspects of transcriptional and translational regulation of AE gene products in kidney of mutant and parental mouse strains and in cultured kidney cells. ..
  6. RBC Ion Transporters as Hemoglobinopathy Risk Modifiers
    Seth Alper; Fiscal Year: 2006
    ..The proposed experiments will increase understanding of sickle cell disease and thalassemia by providing mouse models for genetic tests of new drug therapies under development for near-term clinical testing. ..
  7. ION CHANNEL REGULATION BY THE CYTOPLASMIC TAIL OF PDK1
    Seth Alper; Fiscal Year: 2005
    ..We will search for novel interacting proteins, and prepare protein suitable for structural analysis. ..
  8. ION CHANNEL REGULATION BY THE CYTOPLASMIC TAIL OF PDK1
    Seth Alper; Fiscal Year: 2004
    ..We will search for novel interacting proteins, and prepare protein suitable for structural analysis. ..
  9. ION CHANNEL REGULATION BY THE CYTOPLASMIC TAIL OF PDK1
    Seth Alper; Fiscal Year: 2003
    ..We will search for novel interacting proteins, and prepare protein suitable for structural analysis. ..
  10. Sickle Red Cell K+ Transporter Genetics in S. cerevisiae
    Seth Alper; Fiscal Year: 2002
    ..3) (Provisional Aim): Time permitting, to improve, validate, and standardize growth rescue of trk1delta/trk2delta S. cerevisiae by expression in nonpermissive conditions of cDNA encoding the mammalian IK1 K(ca) channel. ..