Steven Kleene

Steven J Kleene , PhD

Professor

Medical Sciences Building
Room G165
231 Albert Sabin Way
Cincinnati, Ohio 45267-0576
Phone 513-558-6099
Fax 513-558-5738
Email Steven.Kleene@uc.edu

Education

Bachelor's Degree: University of Michigan Ann Arbor, MI, 1974 (Organic Chemistry)

Doctoral Degree: University of Wisconsin Madison, WI, 1980 (Biochemistry)

Postdoctoral Fellowship : Northwestern University Evanston, IL., 1982 (Neurobiology)

Research and Practice Interests

The Kleene lab studies signaling in primary cilia as it relates to kidney disease.  Primary cilia are present on most mammalian cells.  They influence fundamental cellular processes, and defects in primary cilia contribute to kidney disease, cancer, and obesity.  Our work focuses on polycystic kidney disease (PKD), a renal disease that is often caused by defects in ion-conducting channels in the primary cilia.  To that end, we have developed a novel method of stably recording the channel activities and calcium signals in the cilia of live renal cells.  We have identified a reagent that activates the ciliary channels and are testing it for possible therapeutic benefit.  The central methods we use are patch-clamp electrophysiology, cell culture, and molecular biology, including CRISPR/Cas9 genome editing.

Positions and Work Experience

1982 -1984 research associate, Northwestern University, Evanston, IL

1984 -1985 research neurobiologist with rank of assistant professor, Northwestern University, Evanston, IL

1985 -1994 research assistant professor, University of Cincinnati, Cincinnati, OH

1994 -1999 research associate professor, University of Cincinnati, Cincinnati, OH

2000 -2005 associate professor, University of Cincinnati, Cincinnati, OH

2005 - professor, University of Cincinnati, Cincinnati, OH

Research Support

Grant: #NIH R21 DK091917 Investigators:Steven J. Kleene, Nancy K. Kleene 07-26-2011 -04-30-2015 NIH/NIDDK Chemosensory Transduction in a Primary Cilium Role:PI $431,750 Active Type:Grant Level:National

Grant: #NIH R01 DC00926 Investigators:Steven J. Kleene 09-28-2001 -08-31-2006 NIH/NIDCD Biophysics of Olfactory Receptor Neurons Role:PI $1,213,442.00 Level:National

Grant: #NIH R01 DC00926 Investigators:Steven J. Kleene 09-30-1996 -08-31-2001 NIH/NIDCD Biophysics of Olfactory Receptor Neurons Role:PI $994,592.00 Completed Type:Grant Level:National

Grant: #NIH R01 DC04203 Investigators:Steven J. Kleene 08-01-1999 -07-31-2005 NIH/NIDCD Olfactory Electrophysiology in Caenorhabditis Elegans Role:PI $1,132,947.00 Completed Type:Grant Level:National

Investigators:Steven J. Kleene, Nancy K. Kleene 07-01-2013 -06-30-2015 The Baltimore PKD Research and Clinical Core Center Electrical Signaling of Wildtype and Mutated Human Polycystin-2 Channels in a Primary Cilium Role:PI Active Type:Grant Level:National

Grant: #NSF DMS-0515989 Investigators:Donald A. French, Steven J. Kleene 09-01-2005 -08-31-2009 NSF, Division of Mathematical Sciences Identification of Ion Channel Distributions in Olfactory Cilia by Mathematical Modeling Role:Co-PI $168,638 Completed Type:Grant Level:National

Grant: #NIH R21 DC03488 Investigators:Steven J. Kleene 09-30-1997 -09-29-1998 NIH/NIDCD Olfactory Electrophysiology in Caenorhabditis elegans Role:PI $71,502 Completed Type:Grant Level:National

Grant: #NIH R01 DC00926 Investigators:Steven J. Kleene 07-01-1993 -06-30-1996 NIH/NIDCD Biophysics of Olfactory Receptor Neurons Role:PI $400,218 Completed Type:Grant Level:National

Grant: #NIH R01 DC00352 Investigators:Robert C. Gesteland, Steven J. Kleene 07-01-1993 -06-30-1996 NIH/NIDCD Voltage Dye Confocal Analysis of Olfactory Transduction Role:Co-Investigator $700,580 Completed Type:Grant

Grant: #NIH R55 DC00926 (Shannon Director's Award) Investigators:Steven J. Kleene 09-30-1991 -06-30-1993 NIH/NIDCD Biophysics of Olfactory Receptor Neurons Role:PI $123,200 Completed Type:Grant

Grant: #NIH BRSG S07 RR05408 Investigators:Steven J. Kleene 06-01-1991 -05-31-1992 NIH Resting Conductance Properties of Olfactory Cilia Role:PI Completed Type:Grant

Grant: #NIH P01 DC00347 (project 3) Investigators:Robert C. Gesteland, Steven J. Kleene 01-01-1991 -12-31-1993 NIH/NIDCD Developmental Biophysics of Olfactory Neurons Role:Co-PI $316,929 (project 3) Completed Type:Grant

Grant: #NIH P01 NS23348 (project 5) Investigators:Steven J. Kleene 04-01-1986 -12-31-1990 NIH Membrane Excitability in Olfactory Cilia Role:PI $440,949 Completed Type:Grant

Grant: #NSF BNS 83-16827 Investigators:Steven J. Kleene 04-01-1984 -03-31-1986 NSF Sensory Mechanisms in Olfactory Cilia Role:PI $147.300 Completed Type:Grant

Grant: #NIH PO1 NS18490 (project 1) Investigators:Robert C. Gesteland, Steven J. Kleene 09-01-1982 -08-31-1983 NIH/NINCDS Development and Regenerative Plasticity in Vertebrate Olfactory Receptors Role:Co-Investigator Completed Type:Grant

Grant: #NIH NRSA NS06600 Investigators:Steven J. Kleene 09-01-1980 -08-31-1982 NIH/NINCDS Biochemical Specificity of Olfactory Receptors Completed Type:Grant

Grant: #8231/DK090868 Investigators:Kleene, Nancy; Kleene, Steven 07-01-2013 -06-30-2014 National Inst of Diabetes and Digestive and Kidney Disease Electrical Signaling of Wildtype and Mutated Human Polycystin-2 Channels in a Primary Cilium Role:PI $50,000.00

Grant: #URC Interdisciplinary awards AY2014-15 Investigators:Dixon, Bradley; Kleene, Steven; Siroky, Brian 05-01-2015 -04-30-2016 UC A Novel Mechanism for Regulation of Renal Urea Transport Role:PI $25,000.00

Investigators:Steven J. Kleene 07-01-2017 -06-30-2019 UAB Hepato/Renal Fibrocystic Diseases Cellular Physiology Resource Pharmacological Activation of TRPP2 to Restore Calcium Levels and Reduce Cystogenesis in ARPKD Role:PI $47,500.00

Grant: #000508172-006-006/P30DK074038 Investigators:Kleene, Steven 07-01-2017 -06-30-2018 National Inst of Diabetes and Digestive and Kidney Disease Pharmacological Activation of TRPP2 to Restore Calcium Levels and Reduce Cystogenesis in ARPKD Role:PI $14,355.00 Awarded Level:Federal

Grant: #F303345-3/U54DK126114 Investigators:Kleene, Steven 07-01-2021 -06-30-2022 University of Maryland at Baltimore Maryland Polycystic Kidney Disease Research and Translation Core Center (MPKD-RTCC) Role:PI 13894.00 Hold Level:Higher Education

Grant: #2019-02 Investigators:Kleene, Nancy; Kleene, Steven 12-01-2019 -06-30-2021 Dialysis Clinic, Inc. The Therapeutic Potential of a PC2 Activator in Polycystic Kidney Disease Role:PI $60,000.00

Publications

Peer Reviewed Publications

Siroky, Brian J; Kleene, Nancy K; Kleene, Steven J; Varnell, Charles D; Comer, Raven G; Liu, Jialiu; Lu, Lu; Pachciarz, Nolan W; Bissler, John J; Dixon, Bradley P (2017. ) Primary cilia regulate the osmotic stress response of renal epithelial cells through TRPM3 .American Journal of Physiology Renal Physiology, , 312 ,F791 -F805More Information

Kleene, Steven J; Kleene, Nancy K (2017. ) The native TRPP2-dependent channel of murine renal primary cilia.American Journal of Physiology Renal Physiology, , 309 ,F96 -F108More Information

Nauli, Surya M; Pala, Rajasekharreddy; Kleene, Steven J (2016. ) Calcium channels in primary cilia.Current Opinion in Nephrology and Hypertension, , 25 ,452 -458More Information

Flannery, Richard J; Kleene, Nancy K; Kleene, Steven J (2015. ) A TRPM4-dependent current in murine renal primary cilia.American Journal of Physiology Renal Physiology, , 309 ,F697 -F707More Information

Kleene, Steven J; Van Houten, Judith L (2014. ) Electrical Signaling in Motile and Primary Cilia.Bioscience, , 64 ,1092-1102 More Information

Kleene, Nancy K; Kleene, Steven J (2012. ) A method for measuring electrical signals in a primary cilium.Cilia, , 1 ,17 More Information

Griff, Edwin R; Kleene, Nancy K; Kleene, Steven J (2012. ) A selective PMCA inhibitor does not prolong the electroolfactogram in mouse.PLoS ONE, , 7 ,e37148 More Information

French, Donald A; Badamdorj, Dorjsuren; Kleene, Steven J (2010. ) Spatial distribution of calcium-gated chloride channels in olfactory cilia.PLoS ONE, , 5 ,e15676 More Information

Kleene, Steven J (2009. ) Identifying olfaction's 'other channels'.The Journal of Physiology, , 587 ,4135-4136 More Information

Kleene, Steven J (2009. ) Limits of calcium clearance by plasma membrane calcium ATPase in olfactory cilia.PLoS ONE, , 4 ,e5266 More Information

Kleene, Steven J (2008. ) The electrochemical basis of odor transduction in vertebrate olfactory cilia.Chemical Senses, , 33 ,839-859 More Information

Badamdorj, Dorjsuren; Edwards, David A; French, Donald A; Kleene, Steven J (2008. ) Identification of Cl(Ca) channel distributions in olfactory cilia.Mathematical Methods in the Applied Sciences, , 31 ,1860-1873 More Information

Smith, David W; Thach, Sokunthirith; Marshall, Erika L; Mendoza, Mary-Grace; Kleene, Steven J (2008. ) Mice lacking NKCC1 have normal olfactory sensitivity.Physiology & Behavior, , 93 ,44-49 More Information

Nickell, William T; Kleene, Nancy K; Kleene, Steven J (2007. ) Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium.The Journal of Physiology, , 583 ,1005-1020 More Information

Flannery, Richard J; French, Donald A; Kleene, Steven J (2006. ) Clustering of cyclic-nucleotide-gated channels in olfactory cilia.Biophysical Journal, , 91 ,179-188 More Information

French, Donald A; Flannery, Richard J; Groetsch, Charles W; Krantz, Willam B; Kleene, Steven J (2006. ) Numerical approximation of solutions of a nonlinear inverse problem arising in olfaction experimentation.Mathematical and Computer Modelling, , 43 (7-8 ) ,945-956 More Information

Nickell, William T; Kleene, Nancy K; Gesteland, Robert C; Kleene, Steven J (2006. ) Neuronal chloride accumulation in olfactory epithelium of mice lacking NKCC1.Journal of Neurophysiology, , 95 ,2003-2006 More Information

Pun, Raymund Y K; Kleene, Steven J (2004. ) An estimate of the resting membrane resistance of frog olfactory receptor neurones.The Journal of Physiology, , 559 ,535-542 More Information

Pun, Raymund Y K; Kleene, Steven J (2003. ) Contribution of cyclic-nucleotide-gated channels to the resting conductance of olfactory receptor neurons.Biophysical Journal, , 84 ,3425-3435 More Information

Pun, Raymund Y K; Kleene, Steven J (2002. ) Outward currents in olfactory receptor neurons activated by odorants and by elevation of cyclic AMP.Cell Biochemistry and Biophysics, , 37 ,15-26 More Information

Nickell, W T; Pun, R Y K; Bargmann, C I; Kleene, S J (2002. ) Single ionic channels of two Caenorhabditis elegans chemosensory neurons in native membrane.The Journal of Membrane Biology, , 189 ,55-66 More Information

Kleene, S J (2000. ) Spontaneous gating of olfactory cyclic-nucleotide-gated channels.The Journal of Membrane Biology, , 178 ,49-54 More Information

Frings, S; Reuter, D; Kleene, S J (2000. ) Neuronal Ca2+ -activated Cl- channels--homing in on an elusive channel species.Progress in Neurobiology, , 60 ,247-289 More Information

Kleene, S J (1999. ) Both external and internal calcium reduce the sensitivity of the olfactory cyclic-nucleotide-gated channel to cAMP .Journal of Neurophysiology, , 81 ,2675-2682

Kleene, S J (1997. ) High-gain, low-noise amplification in olfactory transduction.Biophysical Journal, , 73 ,1110-1117 More Information

Larsson, H P; Kleene, S J; Lecar, H (1997. ) Noise analysis of ion channels in non-space-clamped cables: estimates of channel parameters in olfactory cilia.Biophysical Journal, , 72 ,1193-1203 More Information

Kleene, S J; Pun, R Y (1996. ) Persistence of the olfactory receptor current in a wide variety of extracellular environments .Journal of Neurophysiology, , 75 ,1386-1391

Kleene, S J (1995. ) Block by external calcium and magnesium of the cyclic-nucleotide-activated current in olfactory cilia.Neuroscience, , 66 ,1001-1008 More Information

Kleene, S J; Cejtin, H C (1994. ) Solving buffering problems with Mathematica software.Analytical Biochemistry, , 222 ,310-314 More Information

Pun, R Y; Kleene, S J; Gesteland, R C (1994. ) Guanine nucleotides modulate steady-state inactivation of voltage-gated sodium channels in frog olfactory receptor neurons.The Journal of Membrane Biology, , 142 ,103-111 More Information

Kleene, S J; Gesteland, R C; Bryant, S H (1994. ) An electrophysiological survey of frog olfactory cilia .The Journal of Experimental Biology, , 195 ,307-328

Kleene, S J (1994. ) Inhibition of olfactory cyclic nucleotide-activated current by calmodulin antagonists .British Journal of Pharmacology, , 111 ,469-472

Kleene, S J (1993. ) Origin of the chloride current in olfactory transduction.Neuron, , 11 ,123-132 More Information

Kleene, S J (1993. ) The cyclic nucleotide-activated conductance in olfactory cilia: effects of cytoplasmic Mg2+ and Ca2+.The Journal of Membrane Biology, , 131 ,237-243 More Information

Kleene, S J (1993. ) A simple intrapipette salt bridge.Journal of Neuroscience Methods, , 46 ,11-16 More Information

Kleene, S J (1992. ) Basal conductance of frog olfactory cilia.Pflügers Archiv : European Journal of Physiology, , 421 ,374-380 More Information

Kleene, S J; Gesteland, R C (1991. ) Calcium-activated chloride conductance in frog olfactory cilia .The Journal of Neuroscience, , 11 ,3624-3629

Kleene, S J; Gesteland, R C (1991. ) Transmembrane currents in frog olfactory cilia.The Journal of Membrane Biology, , 120 ,75-81 More Information

Lidow, M S; Gesteland, R C; Shipley, M T; Kleene, S J (1987. ) Comparative study of immature and mature olfactory receptor cells in adult frogs.Developmental Brain Research, , 31 ,243-258 More Information

Lidow, M S; Kleene, S J; Gesteland, R C (1986. ) Suppression of mitotic activity and synchronization of cell development in olfactory epithelium.Developmental Brain Research, , 28 ,145-162 More Information

Kleene, S J (1986. ) Bacterial chemotaxis and vertebrate olfaction.Experientia, , 42 ,241-250 More Information

Kleene, S J; Gesteland, R C (1983. ) Dissociation of frog olfactory epithelium.Journal of Neuroscience Methods, , 9 ,173-183 More Information

Kleene, S J; Gesteland, R C (1981. ) Dissociation of frog olfactory epithelium with N-ethylmaleimide.Brain Research, , 229 ,536-540 More Information

Kleene, S J; Hobson, A C; Adler, J (1979. ) Attractants and repellents influence methylation and demethylation of methyl-accepting chemotaxis proteins in an extract of Escherichia coli.Proceedings of the National Academy of Sciences of the United States of America, , 76 ,6309-6313 More Information

Kleene, S J; Toews, M L; Adler, J (1977. ) Isolation of glutamic acid methyl ester from an Escherichia coli membrane protein involved in chemotaxis .The Journal of Biological Chemistry, , 252 ,3214-3218

Kleene, Steven J; Siroky, Brian J; Landero-Figueroa, Julio A; Dixon, Brian P; Pachciarz, Nolan W; Lu, Lu; and Kleene, Nancy K. (2019. ) The TRPP2-dependent channel of renal primary cilia also requires TRPM3.PLoS ONE, , 14 ,e0214053. More Information

Kleene, Steven J; Kleene, Nancy K (2021. ) Inward calcium current through the polycystin-2-dependent channels of renal primary cilia.American Journal of Physiology Renal Physiology, , 320 ,F1165 -F1173More Information

Keywords

Chemical Senses,Chloride Channels,Cyclic-nucleotide-gated Channels,Electrophysiology,Neurobiology,Olfaction,Sensory Transduction

Contact Information

Academic - Medical Sciences Building
Room G165
Cincinnati  Ohio, 45267-0576
Phone: 513-558-6099
Fax: 513-558-5738
Steven.Kleene@uc.edu