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Keith Nehrke, Ph.D.

Keith Nehrke, Ph.D.


Research Lab

Our focus is on integrative physiology, and in particular on understanding the molecular mechanisms whereby bioenergetic responses influence metabolic plasticity, survival, and behavior in a whole organism.

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About Me

Faculty Appointments

Professor - Department of Medicine, Nephrology (SMD)

Professor - Department of Pharmacology and Physiology (SMD) - Joint


Post-doctoral Training & Residency

Center for Oral Biology, University of Rochester Medical Center under Dr. Larry Tabak 1994 - 1997


PhD | Univ Rochester Sch Med/Dent. Biochemistry. 1994

MS | Univ Rochester Sch Med/Dent. Biochemistry. 1992

BS | St Univ at Binghamton. Biochemistry. 1989


The focus of my laboratory is on integrative physiology, and in particular on understanding the molecular mechanisms whereby bioenergetic responses influence metabolic plasticity, survival, and behavior in a whole organism. Our goal is to develop a deeper understanding of how these cell physiologic ...
The focus of my laboratory is on integrative physiology, and in particular on understanding the molecular mechanisms whereby bioenergetic responses influence metabolic plasticity, survival, and behavior in a whole organism. 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. Recent focuses have been on mitochondrial ion flux, proteostasis and trans-organelle signaling pathways that regulate hypoxic sensitivity. We believe that combining physiology and genetics provides synergistic value in deciphering mechanisms whereby cells communicate information in their native context. My unique, diverse background has helped my lab to harness the power of new tools such as CRISPR-Cas9 genome editing while translating our findings from the genetic model organism C. elegans to mammalian models such as mice. And collaboration being the heart-and-soul of science, we are pleased to be able to interact with our colleagues in a collegial and inclusive atmosphere where everyone's unique contributions to the team are valued.


Journal Articles

Site-specific phosphorylation of tau impacts mitochondrial function and response to stressors.

Isei MO, Girardi PA, Rodwell-Bullock J, Nehrke K, Johnson GVW

Journal of neurochemistry.. 2023 October 3 Epub 10/03/2023.

Blocking Mitochondrial Pyruvate Transport Alters Corneal Myofibroblast Phenotype: A New Target for Treating Fibrosis.

Jeon KI, Kumar A, Callan CL, DeMagistris M, MacRae S, Nehrke K, Huxlin KR

Investigative ophthalmology & visual science.. 2023 October 364 (13):36. Epub 1900 01 01.

Site-specific phosphorylation of tau impacts mitochondrial biology and response to stressors.

Isei MO, Girardi PA, Rodwell-Bullock J, Nehrke K, Johnson GV

bioRxiv : the preprint server for biology.. 2023 February 19 Epub 02/19/2023.

Selective Disruption of Drp1-Independent Mitophagy and Mitolysosome Trafficking by an Alzheimer's Disease Relevant Tau Modification in a Novel C. elegans Model.

Guha S, Cheng A, Carroll T, King D, Koren SA, Swords S, Nehrke K, Johnson GVW

Genetics.. 2022 August 2 Epub 08/02/2022.

Distinct roles for two acid-sensing ion channels in an ultradian clock.

Kaulich E, Carroll T, Ackley B, Tang YQ, Hardege I, Nehrke K, Schafer WR, Walker DS

eLife.. 2022 June 611 Epub 06/06/2022.

Defining the Role of Mitochondrial Fission in Corneal Myofibroblast Differentiation.

Jeon KI, Kumar A, Wozniak KT, Nehrke K, Huxlin KR

Investigative ophthalmology & visual science.. 2022 April 163 (4):2. Epub 1900 01 01.

Tau Post-Translational Modifications: Potentiators of Selective Vulnerability in Sporadic Alzheimer's Disease.

Carroll T, Guha S, Nehrke K, Johnson GVW

Biology.. 2021 October 1510 (10)Epub 10/15/2021.

FNDC-1-Mediated Mitophagy and ATFS-1 Coordinate to Protect Against Hypoxia-Reoxygenation.

Lim Y, Berry B, Viteri S, McCall M, Park EC, Rongo C, Brookes PS, Nehrke K

Autophagy.. 2021 January 8 Epub 01/08/2021.

Tauopathy-associated tau modifications selectively impact neurodegeneration and mitophagy in a novel C. elegans single-copy transgenic model.

Guha S, Fischer S, Johnson GVW, Nehrke K

Molecular neurodegeneration.. 2020 November 915 (1):65. Epub 11/09/2020.

A T231E Mutant that Mimics Pathologic Phosphorylation of Tau in Alzheimer's disease Causes Activation of the Mitochondrial Unfolded Protein Response in touch neurons.

Guha S, Fischer S, Cheng A, Johnson GVW, Nehrke K

microPublication biology.. 2020 September 92020 Epub 09/09/2020.

Semaphorin 3A potentiates the profibrotic effects of transforming growth factor-?1 in the cornea.

Jeon KI, Nehrke K, Huxlin KR

Biochemical and biophysical research communications.. 2019 October 24 Epub 10/24/2019.

Fndc-1 contributes to paternal mitochondria elimination in C. elegans.

Lim Y, Rubio-Peña K, Sobraske PJ, Molina PA, Brookes PS, Galy V, Nehrke K

Developmental biology.. 2019 October 1454 (1):15-20. Epub 06/21/2019.

Cardioprotection by the mitochondrial unfolded protein response requires ATF5.

Wang YT, Lim Y, McCall MN, Huang KT, Haynes CM, Nehrke K, Brookes PS

American journal of physiology. Heart and circulatory physiology.. 2019 August 1317 (2):H472-H478. Epub 07/05/2019.

Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH.

Nadtochiy SM, Wang YT, Nehrke K, Munger J, Brookes PS

Journal of molecular and cellular cardiology.. 2018 August 121 :155-162. Epub 06/26/2018.

Cardiac metabolic effects of K1.2 channel deletion and evidence for its mitochondrial localization.

Smith CO, Wang YT, Nadtochiy SM, Miller JH, Jonas EA, Dirksen RT, Nehrke K, Brookes PS

FASEB journal : official publication of the Federation of American Societies for Experimental Biology.. 2018 June 4 :fj201800139R. Epub 06/04/2018.

Potential mechanisms linking SIRT activity and hypoxic 2-hydroxyglutarate generation: no role for direct enzyme (de)acetylation.

Nadtochiy SM, Wang YT, Zhang J, Nehrke K, Schafer X, Welle K, Ghaemmaghami S, Munger J, Brookes PS

The Biochemical journal.. 2017 August 10474 (16):2829-2839. Epub 08/10/2017.

The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection.

Smith CO, Nehrke K, Brookes PS

The Biochemical journal.. 2017 June 9474 (12):2067-2094. Epub 06/09/2017.

Acidic pH Is a Metabolic Switch for 2-Hydroxyglutarate Generation and Signaling.

Nadtochiy SM, Schafer X, Fu D, Nehrke K, Munger J, Brookes PS

The Journal of biological chemistry.. 2016 September 16291 (38):20188-97. Epub 08/10/2016.

Chromophore-Assisted Light Inactivation of Mitochondrial Electron Transport Chain Complex II in Caenorhabditis elegans.

Wojtovich AP, Wei AY, Sherman TA, Foster TH, Nehrke K

Scientific reports.. 2016 July 216 :29695. Epub 07/21/2016.

Cardiac Slo2.1 Is Required for Volatile Anesthetic Stimulation of K+ Transport and Anesthetic Preconditioning.

Wojtovich AP, Smith CO, Urciuoli WR, Wang YT, Xia XM, Brookes PS, Nehrke K

Anesthesiology.. 2016 May 124 (5):1065-76. Epub 1900 01 01.

Calcineurin homologous proteins regulate the membrane localization and activity of sodium/proton exchangers in C. elegans.

Allman E, Wang Q, Walker RL, Austen M, Peters MA, Nehrke K

American journal of physiology. Cell physiology.. 2016 February 1310 (3):C233-42. Epub 11/11/2015.

The Mitochondrial Unfolded Protein Response Protects against Anoxia in Caenorhabditis elegans.

Peña S, Sherman T, Brookes PS, Nehrke K

PloS one.. 2016 11 (7):e0159989. Epub 07/26/2016.

Expression of the CHOP-inducible carbonic anhydrase CAVI-b is required for BDNF-mediated protection from hypoxia

Matthews, T. A.; Abel, A.; Demme, C.; Sherman, T.; Pan, P. W.; Halterman, M. W.; Parkkila, S.; Nehrke, K.;.

2014; 1543: 28-37.

An anoxia-starvation model for ischemia/reperfusion in C. elegans

Queliconi, B. B.; Kowaltowski, A. J.; Nehrke, K.;.

2014; .

Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans

Coburn, C.; Allman, E.; Mahanti, P.; Benedetto, A.; Cabreiro, F.; Pincus, Z.; Matthijssens, F.; Araiz, C.; Mandel, A.; Vlachos, M.; Edwards, S. A.; Fischer, G.; Davidson, A.; Pryor, R. E.; Stevens, A.; Slack, F. J.; Tavernarakis, N.; Braeckman, B. P.; Schroeder, F. C.; Nehrke, K.; Gems, D.;.

2013; 11(7): e1001613.

Bicarbonate modulates oxidative and functional damage in ischemia-reperfusion

Queliconi, B. B.; Marazzi, T. B.; Vaz, S. M.; Brookes, P. S.; Nehrke, K.; Augusto, O.; Kowaltowski, A. J.;.

2013; 55: 46-53.

A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

Wojtovich, A. P.; Nadtochiy, S. M.; Urciuoli, W. R.; Smith, C. O.; Grunnet, M.; Nehrke, K.; Brookes, P. S.;.

2013; 1: e48.

Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel

Wojtovich, A. P.; Smith, C. O.; Haynes, C. M.; Nehrke, K. W.; Brookes, P. S.;.

2013; 1827(5): 598-611.

Kir6.2 is not the mitochondrial KATP channel but is required for cardioprotection by ischemic preconditioning

Wojtovich, A. P.; Urciuoli, W. R.; Chatterjee, S.; Fisher, A. B.; Nehrke, K.; Brookes, P. S.;.

2013; 304(11): H1439-45.

miR-786 regulation of a fatty-acid elongase contributes to rhythmic calcium-wave initiation in C. elegans

Kemp, B. J.; Allman, E.; Immerman, L.; Mohnen, M.; Peters, M. A.; Nehrke, K.; Abbott, A. L.;.

2012; 22(23): 2213-20.

Sex modifies genetic effects on residual variance in urinary calcium excretion in rat (Rattus norvegicus)

Perry, G. M.; Nehrke, K. W.; Bushinsky, D. A.; Reid, R.; Lewandowski, K. L.; Hueber, P.; Scheinman, S. J.;.

2012; 191(3): 1003-13.

Identification of a nuclear carbonic anhydrase in Caenorhabditis elegans

Sherman, T. A.; Rongali, S. C.; Matthews, T. A.; Pfeiffer, J.; Nehrke, K.;.

2012; 1823(4): 808-17.

Ischemic preconditioning: the role of mitochondria and aging

Wojtovich, A. P.; Nadtochiy, S. M.; Brookes, P. S.; Nehrke, K.;.

2012; 47(1): 1-7.

A calcineurin homologous protein is required for sodium-proton exchange events in the C. elegans intestine

Wagner, J.; Allman, E.; Taylor, A.; Ulmschneider, K.; Kovanda, T.; Ulmschneider, B.; Nehrke, K.; Peters, M. A.;.

2011; 301(6): C1389-403.

SLO-2 is cytoprotective and contributes to mitochondrial potassium transport

Wojtovich, A. P.; Sherman, T. A.; Nadtochiy, S. M.; Urciuoli, W. R.; Brookes, P. S.; Nehrke, K.;.

2011; 6(12): e28287.

A novel mitochondrial K(ATP) channel assay

Wojtovich, A. P.; Williams, D. M.; Karcz, M. K.; Lopes, C. M.; Gray, D. A.; Nehrke, K. W.; Brookes, P. S.;.

2010; 106(7): 1190-6.

Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1

Frick, K. K.; Krieger, N. S.; Nehrke, K.; Bushinsky, D. A.;.

2009; 24(2): 305-13.

Oscillatory transepithelial H(+) flux regulates a rhythmic behavior in C. elegans

Pfeiffer, J.; Johnson, D.; Nehrke, K.;.

2008; 18(4): 297-302.

The C. elegans mitochondrial K+(ATP) channel: a potential target for preconditioning

Wojtovich, A. P.; Burwell, L. S.; Sherman, T. A.; Nehrke, K. W.; Brookes, P. S.;.

2008; 376(3): 625-8.

Genetic hypercalciuric stone-forming rats

Bushinsky, D. A.; Frick, K. K.; Nehrke, K.;.

2006; 15(4): 403-18.

Altered gating and regulation of a carboxy-terminal ClC channel mutant expressed in the Caenorhabditis elegans oocyte

Denton, J.; Nehrke, K.; Yin, X.; Beld, A. M.; Strange, K.;.

2006; 290(4): C1109-18.

Carboxy terminus splice variation alters ClC channel gating and extracellular cysteine reactivity

He, L.; Denton, J.; Nehrke, K.; Strange, K.;.

2006; 90(10): 3570-81.

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

Yan, X.; Xing, J.; Lorin-Nebel, C.; Estevez, A. Y.; Nehrke, K.; Lamitina, T.; Strange, K.;.

2006; 128(4): 443-59.

Quantitative analysis of the voltage-dependent gating of mouse parotid ClC-2 chloride channel

de Santiago, J. A.; Nehrke, K.; Arreola, J.;.

2005; 126(6): 591-603.

GCK-3, a newly identified Ste20 kinase, binds to and regulates the activity of a cell cycle-dependent ClC anion channel

Denton, J.; Nehrke, K.; Yin, X.; Morrison, R.; Strange, K.;.

2005; 125(2): 113-25.

The abts and sulp families of anion transporters from Caenorhabditis elegans

Sherman, T.; Chernova, M. N.; Clark, J. S.; Jiang, L.; Alper, S. L.; Nehrke, K.;.

2005; 289(2): C341-51.

Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4

Begenisich, T.; Nakamoto, T.; Ovitt, C. E.; Nehrke, K.; Brugnara, C.; Alper, S. L.; Melvin, J. E.;.

2004; 279(46): 47681-7.

Genome-wide search and identification of a novel gel-forming mucin MUC19/Muc19 in glandular tissues

Chen, Y.; Zhao, Y. H.; Kalaslavadi, T. B.; Hamati, E.; Nehrke, K.; Le, A. D.; Ann, D. K.; Wu, R.;.

2004; 30(2): 155-65.

Alternative splicing of N- and C-termini of a C. elegans ClC channel alters gating and sensitivity to external Cl- and H+

Denton, J.; Nehrke, K.; Rutledge, E.; Morrison, R.; Strange, K.;.

2004; 555(Pt 1): 97-114.

The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells

Hoffman, J. F.; Joiner, W.; Nehrke, K.; Potapova, O.; Foye, K.; Wickrema, A.;.

2003; 100(12): 7366-71.

Active K+ secretion through multiple KCa-type channels and regulation by IKCa channels in rat proximal colon

Joiner, W. J.; Basavappa, S.; Vidyasagar, S.; Nehrke, K.; Krishnan, S.; Binder, H. J.; Boulpaep, E. L.; Rajendran, V. M.;.

2003; 285(1): G185-96.

Molecular identification of Ca2+-activated K+ channels in parotid acinar cells

Nehrke, K.; Quinn, C. C.; Begenisich, T.;.

2003; 284(2): C535-46.

Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene

Arreola, J.; Begenisich, T.; Nehrke, K.; Nguyen, H. V.; Park, K.; Richardson, L.; Yang, B.; Schutte, B. C.; Lamb, F. S.; Melvin, J. E.;.

2002; 545(1): 207-16.

Altered GABAergic function accompanies hippocampal degeneration in mice lacking ClC-3 voltage-gated chloride channels

Dickerson, L. W.; Bonthius, D. J.; Schutte, B. C.; Yang, B.; Barna, T. J.; Bailey, M. C.; Nehrke, K.; Williamson, R. A.; Lamb, F. S.;.

2002; 958(2): 227-50.

Molecular and functional characterization of a murine calcium-activated chloride channel expressed in smooth muscle

Elble, R. C.; Ji, G.; Nehrke, K.; DeBiasio, J.; Kingsley, P. D.; Kotlikoff, M. I.; Pauli, B. U.;.

2002; 277(21): 18586-91.

Loss of hyperpolarization-activated Cl(-) current in salivary acinar cells from Clcn2 knockout mice

Nehrke, K.; Arreola, J.; Nguyen, H. V.; Pilato, J.; Richardson, L.; Okunade, G.; Baggs, R.; Shull, G. E.; Melvin, J. E.;.

2002; 277(26): 23604-11.

The NHX family of Na+-H+ exchangers in Caenorhabditis elegans

Nehrke, K.; Melvin, J. E.;.

2002; 277(32): 29036-44.

Targeted disruption of the Nhe1 gene fails to inhibit beta(1)-adrenergic receptor-induced parotid gland hypertrophy

Melvin, J. E.; Nguyen, H. V.; Nehrke, K.; Schreiner, C. M.; Ten Hagen, K. G.; Scott, W.;.

2001; 280(4): G694-700.

Defective fluid secretion and NaCl absorption in the parotid glands of Na+/H+ exchanger-deficient mice

Park, K.; Evans, R. L.; Watson, G. E.; Nehrke, K.; Richardson, L.; Bell, S. M.; Schultheis, P. J.; Hand, A. R.; Shull, G. E.; Melvin, J. E.;.

2001; 276(29): 27042-50.

Charge distribution of flanking amino acids inhibits O-glycosylation of several single-site acceptors in vivo

Nehrke, K.; Ten Hagen, K. G.; Hagen, F. K.; Tabak, L. A.;.

1997; 7(8): 1053-60.

Charge distribution of flanking amino acids influences O-glycan acquisition in vivo

Nehrke, K.; Hagen, F. K.; Tabak, L. A.;.

1996; 271(12): 7061-5.

REF2 encodes an RNA-binding protein directly involved in yeast mRNA 3'-end formation

Russnak, R.; Nehrke, K. W.; Platt, T.;.

1995; 15(3): 1689-97.

Overproduced rho factor from p39AS has lysine replacing glutamic acid at residue 155 in the linker region between its RNA and ATP binding domains.

Nehrke KW, Seifried SE, Platt T

Nucleic acids research.. 1992 November 2520 (22):6107. Epub 1900 01 01.

Yeast tRNA ligase mutants are nonviable and accumulate tRNA splicing intermediates.

Phizicky EM, Consaul SA, Nehrke KW, Abelson J

The Journal of biological chemistry.. 1992 March 5267 (7):4577-82. Epub 1900 01 01.


Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. (2012)

Chapter: The inositol 1,4,5-trisphospate receptor in C. elegans

Authors: Allman E., Thyagarajan B., and Nehrke K.

Publisher: Wiley 2012

Intracellular pH measurements in vivo using green fluorescent protein variants. (2006)

Authors: Nehrke K.

Publisher: Methods Mol Biol. 2006

Current Topics in Membranes (2002)

Chapter: Ca2+-Activated Cl- Currents in Salivary and Lacrimal Glands.

Authors: Melvin J.E., Arreola J., Nehrke K., and Begenisich, T.

Publisher: Academic Press, San Diego 2002

Techniques in Glycobiology (1997)

Chapter: Experimental Approaches to Studying O-Glycosylation In Vivo.

Authors: Nehrke K., Hagen F.H., and Tabak, L.A.

Publisher: Marcel Dekker, New York 1997