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Keith Nehrke

TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentMedicine
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 675
Rochester NY 14642
Other Positions
TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentPharmacology and Physiology

 
 Overview
The focus of my laboratory is on integrative physiology, and in particular on understanding how membrane electrolyte flux and pH regulation influences viability and behavior in the genetic model organism C. elegans. Our approach has been to exploit novel, fluorescent biosensors for measuring physiologic outputs such as calcium, pH, and redox status in unrestrained worms. Our goal is to develop a deeper understanding of how these cell physiologic processes are integrated to mediate the environmental sensitivity and functional output exhibited by live animals. We believe that this combination of physiology and genetics will allow us to discover unique mechanisms whereby cells communicate information in their native context. My background in mammalian physiology and previous work creating mouse transgenics and gene ablations has helped to allow us translate our findings in worms, as has the congenial atmosphere at the University of Rochester which promotes collaborative efforts. Our lab's funding is currently from the NSF to study calcium and pH synergism during a rhythmic behavior and from the NIH, with co-PI Dr. Paul Brookes, to study ischemic preconditioning in worms. These interactions with other faculty are one of the benefits of working in a multidisciplinary area such as Medicine.

 
 Selected Publications
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  1. Matthews TA, Abel A, Demme C, Sherman T, Pan PW, Halterman MW, Parkkila S, Nehrke K. Expression of the CHOP-inducible carbonic anhydrase CAVI-b is required for BDNF-mediated protection from hypoxia. Brain Res. 2014 Jan 16; 1543:28-37.
    View in: PubMed
  2. Coburn C, Allman E, Mahanti P, Benedetto A, Cabreiro F, Pincus Z, Matthijssens F, Araiz C, Mandel A, Vlachos M, Edwards SA, Fischer G, Davidson A, Pryor RE, Stevens A, Slack FJ, Tavernarakis N, Braeckman BP, Schroeder FC, Nehrke K, Gems D. Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans. PLoS Biol. 2013 Jul; 11(7):e1001613.
    View in: PubMed
  3. Wojtovich AP, Urciuoli WR, Chatterjee S, Fisher AB, Nehrke K, Brookes PS. Kir6.2 is not the mitochondrial KATP channel but is required for cardioprotection by ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2013 Jun; 304(11):H1439-45.
    View in: PubMed
  4. Wojtovich AP, Nadtochiy SM, Urciuoli WR, Smith CO, Grunnet M, Nehrke K, Brookes PS. A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel. Peerj. 2013; 1:e48.
    View in: PubMed
  5. Allman E, Waters K, Ackroyd S, Nehrke K. Analysis of Ca2+ Signaling Motifs That Regulate Proton Signaling through the Na+/H+ Exchanger NHX-7 during a Rhythmic Behavior in Caenorhabditis elegans. J Biol Chem. 2013 Feb 22; 288(8):5886-95.
    View in: PubMed
  6. Wojtovich AP, Smith CO, Haynes CM, Nehrke KW, Brookes PS. Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel. Biochim Biophys Acta. 2013 May; 1827(5):598-611.
    View in: PubMed
  7. Queliconi BB, Marazzi TB, Vaz SM, Brookes PS, Nehrke K, Augusto O, Kowaltowski AJ. Bicarbonate modulates oxidative and functional damage in ischemia-reperfusion. Free Radic Biol Med. 2013 Feb; 55:46-53.
    View in: PubMed
  8. Kemp BJ, Allman E, Immerman L, Mohnen M, Peters MA, Nehrke K, Abbott AL. miR-786 Regulation of a Fatty-Acid Elongase Contributes to Rhythmic Calcium-Wave Initiation in C. elegans. Curr Biol. 2012 Dec 4; 22(23):2213-20.
    View in: PubMed
  9. Portal-Celhay C, Nehrke K, Blaser MJ. Effect of Caenorhabditis elegans age and genotype on horizontal gene transfer in intestinal bacteria. FASEB J. 2013 Feb; 27(2):760-8.
    View in: PubMed
  10. Perry GM, Nehrke KW, Bushinsky DA, Reid R, Lewandowski KL, Hueber P, Scheinman SJ. Sex modifies genetic effects on residual variance in urinary calcium excretion in rat (Rattus norvegicus). Genetics. 2012 Jul; 191(3):1003-13.
    View in: PubMed
  11. Wojtovich AP, DiStefano P, Sherman T, Brookes PS, Nehrke K. Mitochondrial ATP-sensitive potassium channel activity and hypoxic preconditioning are independent of an inwardly rectifying potassium channel subunit in Caenorhabditis elegans. FEBS Lett. 2012 Feb 17; 586(4):428-34.
    View in: PubMed
  12. Johnson D, Allman E, Nehrke K. Regulation of acid-base transporters by reactive oxygen species following mitochondrial fragmentation. Am J Physiol Cell Physiol. 2012 Apr 1; 302(7):C1045-54.
    View in: PubMed
  13. Sherman TA, Rongali SC, Matthews TA, Pfeiffer J, Nehrke K. Identification of a nuclear carbonic anhydrase in Caenorhabditis elegans. Biochim Biophys Acta. 2012 Apr; 1823(4):808-17.
    View in: PubMed
  14. Wojtovich AP, Sherman TA, Nadtochiy SM, Urciuoli WR, Brookes PS, Nehrke K. SLO-2 is cytoprotective and contributes to mitochondrial potassium transport. PLoS One. 2011; 6(12):e28287.
    View in: PubMed
  15. Wojtovich AP, Nadtochiy SM, Brookes PS, Nehrke K. Ischemic preconditioning: the role of mitochondria and aging. Exp Gerontol. 2012 Jan; 47(1):1-7.
    View in: PubMed
  16. Wagner J, Allman E, Taylor A, Ulmschneider K, Kovanda T, Ulmschneider B, Nehrke K, Peters MA. A calcineurin homologous protein is required for sodium-proton exchange events in the C. elegans intestine. Am J Physiol Cell Physiol. 2011 Dec; 301(6):C1389-403.
    View in: PubMed
  17. Wojtovich AP, Nehrke KW, Brookes PS. The mitochondrial complex II and ATP-sensitive potassium channel interaction: quantitation of the channel in heart mitochondria. Acta Biochim Pol. 2010; 57(4):431-4.
    View in: PubMed
  18. Johnson D, Nehrke K. Mitochondrial fragmentation leads to intracellular acidification in Caenorhabditis elegans and mammalian cells. Mol Biol Cell. 2010 Jul 1; 21(13):2191-201.
    View in: PubMed
  19. Wojtovich AP, Williams DM, Karcz MK, Lopes CM, Gray DA, Nehrke KW, Brookes PS. A novel mitochondrial K(ATP) channel assay. Circ Res. 2010 Apr 16; 106(7):1190-6.
    View in: PubMed
  20. Allman E, Johnson D, Nehrke K. Loss of the apical V-ATPase a-subunit VHA-6 prevents acidification of the intestinal lumen during a rhythmic behavior in C. elegans. Am J Physiol Cell Physiol. 2009 Nov; 297(5):C1071-81.
    View in: PubMed
  21. Frick KK, Krieger NS, Nehrke K, Bushinsky DA. Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1. J Bone Miner Res. 2009 Feb; 24(2):305-13.
    View in: PubMed
  22. Wojtovich AP, Burwell LS, Sherman TA, Nehrke KW, Brookes PS. The C. elegans mitochondrial K+(ATP) channel: a potential target for preconditioning. Biochem Biophys Res Commun. 2008 Nov 21; 376(3):625-8.
    View in: PubMed
  23. Pfeiffer J, Johnson D, Nehrke K. Oscillatory transepithelial H(+) flux regulates a rhythmic behavior in C. elegans. Curr Biol. 2008 Feb 26; 18(4):297-302.
    View in: PubMed
  24. Nehrke K, Denton J, Mowrey W. Intestinal Ca2+ wave dynamics in freely moving C. elegans coordinate execution of a rhythmic motor program. Am J Physiol Cell Physiol. 2008 Jan; 294(1):C333-44.
    View in: PubMed
  25. Yan X, Xing J, Lorin-Nebel C, Estevez AY, Nehrke K, Lamitina T, Strange K. Function of a STIM1 homologue in C. elegans: evidence that store-operated Ca2+ entry is not essential for oscillatory Ca2+ signaling and ER Ca2+ homeostasis. J Gen Physiol. 2006 Oct; 128(4):443-59.
    View in: PubMed
  26. Bushinsky DA, Frick KK, Nehrke K. Genetic hypercalciuric stone-forming rats. Curr Opin Nephrol Hypertens. 2006 Jul; 15(4):403-18.
    View in: PubMed
  27. He L, Denton J, Nehrke K, Strange K. Carboxy terminus splice variation alters ClC channel gating and extracellular cysteine reactivity. Biophys J. 2006 May 15; 90(10):3570-81.
    View in: PubMed
  28. Strange K, Denton J, Nehrke K. Ste20-type kinases: evolutionarily conserved regulators of ion transport and cell volume. Physiology (Bethesda). 2006 Feb; 21:61-8.
    View in: PubMed
  29. Nehrke K. Intracellular pH measurements in vivo using green fluorescent protein variants. Methods Mol Biol. 2006; 351:223-39.
    View in: PubMed
  30. Denton J, Nehrke K, Yin X, Beld AM, Strange K. Altered gating and regulation of a carboxy-terminal ClC channel mutant expressed in the Caenorhabditis elegans oocyte. Am J Physiol Cell Physiol. 2006 Apr; 290(4):C1109-18.
    View in: PubMed
  31. de Santiago JA, Nehrke K, Arreola J. Quantitative analysis of the voltage-dependent gating of mouse parotid ClC-2 chloride channel. J Gen Physiol. 2005 Dec; 126(6):591-603.
    View in: PubMed
  32. Sherman T, Chernova MN, Clark JS, Jiang L, Alper SL, Nehrke K. The abts and sulp families of anion transporters from Caenorhabditis elegans. Am J Physiol Cell Physiol. 2005 Aug; 289(2):C341-51.
    View in: PubMed
  33. Denton J, Nehrke K, Yin X, Morrison R, Strange K. GCK-3, a newly identified Ste20 kinase, binds to and regulates the activity of a cell cycle-dependent ClC anion channel. J Gen Physiol. 2005 Feb; 125(2):113-25.
    View in: PubMed
  34. Begenisich T, Nakamoto T, Ovitt CE, Nehrke K, Brugnara C, Alper SL, Melvin JE. Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4. J Biol Chem. 2004 Nov 12; 279(46):47681-7.
    View in: PubMed
  35. Denton J, Nehrke K, Rutledge E, Morrison R, Strange K. Alternative splicing of N- and C-termini of a C. elegans ClC channel alters gating and sensitivity to external Cl- and H+. J Physiol. 2004 Feb 15; 555(Pt 1):97-114.
    View in: PubMed
  36. Nehrke K. A reduction in intestinal cell pHi due to loss of the Caenorhabditis elegans Na+/H+ exchanger NHX-2 increases life span. J Biol Chem. 2003 Nov 7; 278(45):44657-66.
    View in: PubMed
  37. Chen Y, Zhao YH, Kalaslavadi TB, Hamati E, Nehrke K, Le AD, Ann DK, Wu R. Genome-wide search and identification of a novel gel-forming mucin MUC19/Muc19 in glandular tissues. Am J Respir Cell Mol Biol. 2004 Feb; 30(2):155-65.
    View in: PubMed
  38. Hoffman JF, Joiner W, Nehrke K, Potapova O, Foye K, Wickrema A. The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells. Proc Natl Acad Sci U S A. 2003 Jun 10; 100(12):7366-71.
    View in: PubMed
  39. Joiner WJ, Basavappa S, Vidyasagar S, Nehrke K, Krishnan S, Binder HJ, Boulpaep EL, Rajendran VM. Active K+ secretion through multiple KCa-type channels and regulation by IKCa channels in rat proximal colon. Am J Physiol Gastrointest Liver Physiol. 2003 Jul; 285(1):G185-96.
    View in: PubMed
  40. Dickerson LW, Bonthius DJ, Schutte BC, Yang B, Barna TJ, Bailey MC, Nehrke K, Williamson RA, Lamb FS. Altered GABAergic function accompanies hippocampal degeneration in mice lacking ClC-3 voltage-gated chloride channels. Brain Res. 2002 Dec 27; 958(2):227-50.
    View in: PubMed
  41. Arreola J, Begenisich T, Nehrke K, Nguyen HV, Park K, Richardson L, Yang B, Schutte BC, Lamb FS, Melvin JE. Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene. J Physiol. 2002 Nov 15; 545(Pt 1):207-16.
    View in: PubMed
  42. Nehrke K, Quinn CC, Begenisich T. Molecular identification of Ca2+-activated K+ channels in parotid acinar cells. Am J Physiol Cell Physiol. 2003 Feb; 284(2):C535-46.
    View in: PubMed
  43. Nehrke K, Melvin JE. The NHX family of Na+-H+ exchangers in Caenorhabditis elegans. J Biol Chem. 2002 Aug 9; 277(32):29036-44.
    View in: PubMed
  44. Nehrke K, Arreola J, Nguyen HV, Pilato J, Richardson L, Okunade G, Baggs R, Shull GE, Melvin JE. Loss of hyperpolarization-activated Cl(-) current in salivary acinar cells from Clcn2 knockout mice. J Biol Chem. 2002 Jun 28; 277(26):23604-11.
    View in: PubMed
  45. Elble RC, Ji G, Nehrke K, DeBiasio J, Kingsley PD, Kotlikoff MI, Pauli BU. Molecular and functional characterization of a murine calcium-activated chloride channel expressed in smooth muscle. J Biol Chem. 2002 May 24; 277(21):18586-91.
    View in: PubMed
  46. Attaphitaya S, Nehrke K, Melvin JE. Acute inhibition of brain-specific Na(+)/H(+) exchanger isoform 5 by protein kinases A and C and cell shrinkage. Am J Physiol Cell Physiol. 2001 Oct; 281(4):C1146-57.
    View in: PubMed
  47. Yan W, Nehrke K, Choi J, Barber DL. The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor. J Biol Chem. 2001 Aug 17; 276(33):31349-56.
    View in: PubMed
  48. Park K, Evans RL, Watson GE, Nehrke K, Richardson L, Bell SM, Schultheis PJ, Hand AR, Shull GE, Melvin JE. Defective fluid secretion and NaCl absorption in the parotid glands of Na+/H+ exchanger-deficient mice. J Biol Chem. 2001 Jul 20; 276(29):27042-50.
    View in: PubMed
  49. Melvin JE, Nguyen HV, Nehrke K, Schreiner CM, Ten Hagen KG, Scott W. Targeted disruption of the Nhe1 gene fails to inhibit beta(1)-adrenergic receptor-induced parotid gland hypertrophy. Am J Physiol Gastrointest Liver Physiol. 2001 Apr; 280(4):G694-700.
    View in: PubMed
  50. Nehrke K, Begenisich T, Pilato J, Melvin JE. Into ion channel and transporter function. Caenorhabditis elegans ClC-type chloride channels: novel variants and functional expression. Am J Physiol Cell Physiol. 2000 Dec; 279(6):C2052-66.
    View in: PubMed
  51. Hagen FK, Nehrke K. cDNA cloning and expression of a family of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase sequence homologs from Caenorhabditis elegans. J Biol Chem. 1998 Apr 3; 273(14):8268-77.
    View in: PubMed
  52. Nehrke K, Hagen FK, Tabak LA. Isoform-specific O-glycosylation by murine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T3, in vivo. Glycobiology. 1998 Apr; 8(4):367-71.
    View in: PubMed
  53. Nehrke K, Ten Hagen KG, Hagen FK, Tabak LA. Charge distribution of flanking amino acids inhibits O-glycosylation of several single-site acceptors in vivo. Glycobiology. 1997 Dec; 7(8):1053-60.
    View in: PubMed
  54. Nehrke K, Tabak LA. Biosynthesis of a low-molecular-mass rat submandibular gland mucin glycoprotein in COS7 cells. Biochem J. 1997 Apr 15; 323 ( Pt 2):497-502.
    View in: PubMed
  55. Nehrke K, Hagen FK, Tabak LA. Charge distribution of flanking amino acids influences O-glycan acquisition in vivo. J Biol Chem. 1996 Mar 22; 271(12):7061-5.
    View in: PubMed
  56. Russnak R, Nehrke KW, Platt T. REF2 encodes an RNA-binding protein directly involved in yeast mRNA 3'-end formation. Mol Cell Biol. 1995 Mar; 15(3):1689-97.
    View in: PubMed
  57. Nehrke KW, Platt T. A quaternary transcription termination complex. Reciprocal stabilization by Rho factor and NusG protein. J Mol Biol. 1994 Nov 11; 243(5):830-9.
    View in: PubMed
  58. Nehrke KW, Zalatan F, Platt T. NusG alters rho-dependent termination of transcription in vitro independent of kinetic coupling. Gene Expr. 1993; 3(2):119-33.
    View in: PubMed
  59. Nehrke KW, Seifried SE, Platt T. Overproduced rho factor from p39AS has lysine replacing glutamic acid at residue 155 in the linker region between its RNA and ATP binding domains. Nucleic Acids Res. 1992 Nov 25; 20(22):6107.
    View in: PubMed
  60. Phizicky EM, Consaul SA, Nehrke KW, Abelson J. Yeast tRNA ligase mutants are nonviable and accumulate tRNA splicing intermediates. J Biol Chem. 1992 Mar 5; 267(7):4577-82.
    View in: PubMed

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