Keith Nehrke
| Title | Associate Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Medicine |
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| Address | University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 675
Rochester NY 14642
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| Title | Associate Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Pharmacology and Physiology |
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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.
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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.
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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.
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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.
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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.
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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; 302(7):C1045-54.
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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.
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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.
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Wojtovich AP, Nadtochiy SM, Brookes PS, Nehrke K. Ischemic preconditioning: The role of mitochondria and aging. Exp Gerontol. 2012 Jan; 47(1):1-7.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Bushinsky DA, Frick KK, Nehrke K. Genetic hypercalciuric stone-forming rats. Curr Opin Nephrol Hypertens. 2006 Jul; 15(4):403-18.
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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.
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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.
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Nehrke K. Intracellular pH measurements in vivo using green fluorescent protein variants. Methods Mol Biol. 2006; 351:223-39.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Nehrke K, Melvin JE. The NHX family of Na+-H+ exchangers in Caenorhabditis elegans. J Biol Chem. 2002 Aug 9; 277(32):29036-44.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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