Department of Pathology

Paul Koles, M.D., Chair

Peter K. Lauf

Peter K. Lauf, M.D.

Professor of Pathology, University Professor

Cell Biophysics Group
Wright State University
Dayton, Ohio 45435 0001

E-mail: peter.lauf@wright.edu
(937) 775-3025
Fax: (937) 775-2759

Curriculum Vitae

Dr. Peter K. Lauf received his M.D. degree in 1960 at the University of Freiburg, Germany, after his thesis work under neurophysiologist Paul Hoffmann and his successor Albrecht Fleckenstein. From 1960-1962, he was Fellow at the Institute of Pathology at the University of Freiburg. From 1962-1964, he was Research Fellow at the Max Planck Institute of Immunochemistry (Otto Westphal) in Freiburg/Germany. From 1964-1967, he was Research Associate at the Child Research Center of Michigan in Detroit; 1966-67, Assistant Professor of Biochemistry at Wayne State University. In 1968, he joined Dan Tosteson's Department of Physiology and Pharmacology at Duke as Assistant Professor, where he became Associate Professor in 1971 and Professor in 1978. In 1985, he was appointed Chair of the Department of Physiology and Biophysics at Wright State University, a position he held until June 30, 2003.

On July 1, 2003, he assumed his new position as University Professor within the School of Medicine at Wright State University. Dr. Lauf has over 300 publications, book chapters and abstracts. His NIH-funded research was on erythrocyte cation transport system, especially the Na/K pumps and the electroneutral K-Cl cotransporter. During his career, he has trained numerous Ph.D.'s and postdoctoral fellows. He has held visiting professorships in Germany, Japan, Sweden and Australia, and joint appointments in the Department of Immunology at Duke and in Physiology and Biophysics at the University of Cincinnati College of Medicine. Dr. Lauf has received several awards such as an NIH career award in 1971, the Golding Research Professorship at Wright State in 1988, the 1998 Research Award from the Affiliate Society Council of Engineering in Dayton, and the University Professor title at Wright State University in 2003.

Lauf organized the Third International Symposium on Cell Volume and Signaling held at Wright State in 2003. He currently serves as a Sage member of the Chapter Advisory Committee (CAC) of the American Physiological Society, of which he was the founding chair from 2008-2011. CAC is an assembly of  U.S. State Chapters in Physiology, for which the Ohio Physiological Society, originally founded by Lauf in 1986, served as a model.


Control of Erythrocyte Volume Through Membrane Transport Processes

Erythrocytes of all species maintain their cellular volume by active transport of sodium (Na) and potassium (K) through specifically designed pumps counteracting the constant dissipation of inward Na and outward K gradients across their plasma membranes. Using various cellular models, this laboratory has been studying for many years the properties of Na/K pump fluxes, as well as the mechanisms by which K together with chloride (Cl) leaves the cell through a cation-anion coupled transport mechanism, the K-Cl cotransporter. More recently this laboratory's research is attempting to shed further light on the kinetic and thermodynamic properties of K-Cl cotransport because they reveal how the transporter works, how ions bind and are translocated, and which is the nature of the driving forces. It has been discovered that crucial thiol groups, intracellular magnesium, as well as anions and protons are crucial for the regulation of the K-Cl cotransporter's activity through regulatory mechanisms such as enzymes and cofactors still to be revealed. Studies are now in progress on the molecular identity of the K-Cl cotransporter and its regulatory machinery through the use of pharmacological probes such as inhibitors like loop diuretics, disulfonic stilbenes and quinolines, and by molecular-biological techniques aimed at cloning and reconstituting the protein macromolecules. Knowledge gained in these studies will benefit the understanding of disorders of cell volume regulation in general, and of processes leading to cellular dehydration through K-Cl and water loss as it occurs in erythrocytes with genetically abnormal hemoglobins such as hemoglobin S and C.

Selected Publications

Properties and Membrane Transport Mechanisms of Erythrocytes. Peter K. Lauf and Norma C. Adragna. In Erythrocytes: Physiology and Pathophysiology, F. Lang and M Foeller, Eds., Imperial College Press, 2012, p. 57-228.

KCC2a expression in a human fetal lens epithelial cell line. Peter K.Lauf, Mauricio Di Fulvio, Vinita Srivastava, Neelima Sharma, and Norma C Adragna. Cell Physiol Biochem. 29:303-312, 2012.

K-Cl cotransport (COT) in vascular smooth muscle and erythrocytes: Possible implication in vasodilation. N.C. Adragna, R.E. White, S.N. Orlov, and P.K. Lauf. FASEB J., 14:A405, 2000.

Relationship between cell swelling, cell metabolism and activation of erythrocyte K-Cl cotransport (COT) by vasodilators. J. Zhang, P.K. Lauf, and N.C. Adragna. FASEB J., 14:A405, 2000.

Protein kinase G regulates the potassium-chloride cotransporter (KCC)-3 mRNA expressions in primary cultures of rat vascular smooth muscle cells (VSMCs). M. Di Fulvio, P.K. Lauf, and N.C. Adragna. FASEB J., 15:A114, 2001.

KCl Cotransport (COT) Regulation and Protein Kinase G (PKG) in Cultured Vascular Smooth Muscle Cells (VSMCs). N.C. Adragna, J. Zhang, T.M. Lincoln, and P.K. Lauf. FASEB J., 15:A114, 2001

Serum affects RB Influx through Cl-dependent and Cl-independent pathways in Primary Cultured Vascular Smooth Muscle Cells (VSMCs). J. Zhang, P.K. Lauf, and N.C. Adragna. FASEB J., 15:114, 2001.

Platelet-derived growth factor (PDGF) regulates K-Cl COT activity and KCC1/KCC3 mRNA expression in vascular smooth muscle cells (VSMCs). J. Zhang, M. Di Fulvio, P.K. Lauf, and N.C. Adragna. FASEB J., 16:A98, 2002.

Properties of K-Cl Cotransport (COT) in C6 glioma cells. K.B.E. Gagnon, R.E.W. Fyffe, M. Di Fulvio, N.C. Adragna, and P.K. Lauf. FASEB J., 16: A, 2002.

The protein kinase G signaling pathway regulates the potassium-chloride cotransporter-3 (KCC3a and KCC3b) mRNA expression in primary cultures of rat vascular smooth muscle cells. M. Di Fulvio, P.K. Lauf, and N.C. Adragna. FASEB J. 16:A421, Abstract, 2002.

Cloning and expression of sheep K-Cl cotransporter-1. J.J. Zhang, N.C. Adragna, K.B. Gagnon, R.E. Fyffe, and P.K. Lauf. Abstract, FASEB J., 2003.

Severe hypertension in K-Cl cotransporter-3 knock out mice. N.C. Adragna, Y. Chen, E. Delpire, P.K. Lauf, and M. Morris. Abstract, FASEB J., 2003.

Post-translational regulation of K-Cl cotransport (COT) by platelet-derived growth factor (PDGF) is mediated by the phosphoinositide 3-kinase (PI3-K) in vascular smooth muscle cells (VSMCs). J. Zhang, P.K. Lauf, and N.C. Adragna. FASEB J, 2003.

Molecular Regulation of Potassium-Chloride Cotransporter by NONOates. N.C. Adragna, M. Di Fulvio, S. Sha, and P.K. Lauf. IASH Meeting, San Antonio, TX, Abstract, 2003.

Role of K-Cl and Na-K-2Cl cotransport (COT) on Net-K loss in HbA and HbS erythrocytes and the significance of the flux reversal point. N.C. Adragna and P.K. Lauf. Blood, Abstract, 2003.

Membrane localization of the neuronal K-Cl cotransporter (K-Cl COT, KCC2) in rat cerebellum. K.E.B. Gagnon, P.K. Lauf and R.E. W. Fyffe. In: Proceedings of the Dayton International Symposium on Cell Volume and Signaling, Springer Verlag. P.K. Lauf and N.C. Adragna, eds. Advances in Experimental Medicine and Biology Volume 559, 11-29, 2004.

K-Cl cotransport (K-Cl, KCC1) activation by N-ethylmaleimide in C6 glioma cells. K.E.B. Gagnon, N.C. Adragna, R.E.W. Fyffe, and P.K. Lauf. In: Proceedings of the Dayton International Symposium on Cell Volume and Signaling, Springer Verlag. P.K. Lauf and N.C. Adragna, eds. Advances in Experimental Medicine and BiologyVolume 559, 11-29, 2004.

K-Cl Cotransport (COT) is functionally present in a Human Lens Epithelial Cell (HLEC) line (B3). Peter K. Lauf, Ronald Warwar, Thomas L Brown and Norma C. Adragna. FASEB J. 18: 316A, 2004

Thiol-modification by N-ethylmaleimide (NEM) reveals common regulation of Na-K-2Cl and K-Cl Cotransport (COT) in a Human Lens Epithelial Cell (HLEC) line (B3). P.K. Lauf and N.C. Adragna. US-Japan Meeting Cooperative Cataract Research Group, Kona, HI, February 14-18, 2004, 7.6.

K-Cl cotransport-1 expression in vascular smooth muscle cells. N. C. Adragna, C.F. Temprana, A. Sharma and P.K. Lauf, FASEB J19: 671.10 2005.

Molecular and immunochemical evidence for the presence of several KCC isoforms in a human lens epithelial cell line (B3) and lens tissue. S. Misri, A. Chimote, N.C. Adragna, R.E.W. Fyffe, T. L. Brown, R. Warwar and P. K. Lauf. FASEB J, 19: 671.11 abstract 2005.

Potassium Influx Pathway Regulation and KCC Isoforms in Human Lens Epithelial Cells and Tissue. P.K. Lauf, S. Misri, A. Chimote, R. Warwar, T.L Brown and N.C. Adragna. ARVO Meeting, Fort Lauderdale, FL, May 2005. Invest Opthalmol. Vis. Sci., May, 46: 3318, 2005.

Net K loss, K-Cl and Na-K-2Cl cotransport in hemoglobin A and S erythrocytes and significance of the flux reversal point. N.C. Adragna and P.K. Lauf. First International Meeting on Physiology and Pathophysiology of Chloride Transporters and Channels. Soria, Spain, September 19-22, 2005.

Potassium influx regulation and NKCC and KCC isoforms in human lens epithelial cell B3 and tissues from cataractous lenses. P.K. Lauf, S. Misri, A. Chimote, R. Warwar, T.L. Brown, R.E.W. Fyffe, and N.C. Adragna. International Symposium on Cell Volume Control in Health and Disease. Copenhagen, Denmark, Sep 23-27, p. 49, 2005.

Signal transduction mechanisms of K-Cl cotransport regulation and their relationship to disease. N.C. Adragna, C.M. Ferrell, J. Zhang, M. Di Fulvio, C.F. Temprana, A. Sharma, R.E.W. Fyffe, D. R. Cool, and Peter K. Lauf. International Symposium on Cell Volume Control in Health and Disease. Copenhagen, Denmark, September 23-27, p. 66, 2005.

UVB-irradiation targets coupled cation transporters in cultured human lens epithelial cells. P.K. Lauf, S. Misri and N.C. Adragna. US-Japan Meeting Cooperative Cataract Research Group, Kona, HI, October 29-November 3, 2005.

Coupled cation cotransporters (CCC) of cultured human epithelial cells are targets of UVB-irradiation. P.K. Lauf, S. Misri and N.C. Adragna. Greater Lakes Vision Research Conference, Cincinnati, OH, November 11-12, 2005.

Response to hyposmotic challenge of cation-chloride cotransporters (CCC) identified in a primary human epithelial cell line (FHL 124). P.K. Lauf, S. Misri, A.A. Chimote, S. Bhullar and N.C. Adragna. ARVO, 2006.

K-Cl cotransport (KCC) in red blood cells from patients with KCC3 isoform mutants (Corpus Callosum Agenesis with Peripheral Neuropathy, ACCPN, Alderman's Syndrome). P. K. Lauf, N.C. Adragna, N. Dupre, KP Bouchard and G.A. Rouleau. Canadian Society for Biochemistry and Molecular Biology, Symposium on Membrane Proteins in Health and Disease, Niagara-on-the-Lake, ON, Ca, May 30-June 4, 2006.

Chloride determination in human lens epithelial cells (B3) by a fluorescent dye. A.A. Chimote, N.C. Adragna and P.K. Lauf. Experimental Biology Washington, D.C. 2007, FASEB J, 21: 938.13, 2007.

Properties of hyposmotically activated K channels in human lens epithelial cells (FHL124 LECs). P.K. Lauf, S. Misri, A.A. Chimote, S. Ali, P. Fattahi. Experimental Biology Washington, D.C., FASEB J, 21: 938.4, 2007.

Functional characteristics of K-Cl cotransport (COT) in vascular smooth muscle cells. N. C. Adragna, J. Zhang, P.K. Lauf, Experimental Biology Washington, D.C., FASEB J. 21: 938.5, 2007.

Functional regulation of K-Cl cotransport (COT) by the nitric oxide (NO) pathway, vasoconstrictors (VCs) and inhibitors of the contractile apparatus (ICA) in vascular smooth muscle cells (VSMCs). N.C. Adragna and P.K. Lauf. Experimental Biology Washington, D.C., FASEB J, 21: 938.18, 2007.

K-Cl cotransport functional properties and regulation in vascular smooth muscle cells and its relationship to cardiovascular disease. N.C. Adragna, J. Zhang and P.K. Lauf. 6th International Symposium on Cell Volume Regulation in Health and Disease. Salzburg, Austria, Oct. 1-5, 2007.

Ion channels and cotransporters during regulatory volume decrease in human lens epithelial cells. P.K. Lauf, A.A. Chimote, Sandeep Misri and N.C. Adragna. 6th International Symposium on Cell Volume Regulation in Health and Disease. Salzburg, Austria, Oct. 1-5, 2007.

Regulatory volume decrease by intermediate conductance K channels and role of electroneutral cation-chloride cotransporters in human lens epithelial cells. P.K. Lauf, A. A. Chimote, N.C. Adragna. Cooperative US-Japanese Research Group, Kona HI., Dec. 2007.

Na-Cl Cotransport (NCC) in Human Lens Epithelial Cells (LECs). N.C. Adragna, A.A. Chimote, and P.K. Lauf. Cooperative US-Japanese Research Group, Kona HI., Dec. 2007.

Li fluxes Indicate Presence of Na-Cl cotransport (NCC) in Human Lens Epithelial Cells (hLEC's). Norma C. Adragna, Ameet A. Chimote, and Peter K. Lauf. Experimental Biology Annual Meeting, San Diego, CA. April 2008.

Further Characteristics of Hyposmotically-Activated K loss in Human Lens Epithelial Cells (hLEC's) Norma C. Adragna, Ameet A. Chimote, and Peter K. Lauf. Experimental Biology Annual Meeting, San Diego, CA. April 2008.

Role of Rh (rhesus) complex in K-Cl cotransport (KCC) regulation in red blood cells (RBCs) of Rh and Rh-associated glycoprotein (RhAg) knockout (KO) mice. Peter K Lauf, Norma C Adragna, Dominique Goossens, Jean Pierre Cartron. FASEB J. 23: ... 2009.

Erythrocytes constitute the main blood compartment for aluminum. N.C. Adragna and P.K. Lauf, Faseb J 23 :….2009.

KCC2a Expression in a Primary Fetal Human Lens Epithelial Cell (FHLEC) Line.V Srivastava, M Di Fulvio, N Sharma, N C Adragna P K Lauf. Faseb J 2011.

Pharmacological Protein Kinase C (PKC) Isoform Suppression and K (Rb) Transport Changes in a Primary Fetal Human Lens (FHL) Cell Line.M Lepera, N C. Adragna & PK Lauf. Faseb J 2011.

K influx Parameters in Rat Aortic Vascular Smooth Muscle Cells (RASMCS).N. Sharma, PK Lauf, NC Adragna. Faseb J 2011.

Evidence for Participation of Aquaporins during Cell Volume Regulation in Nematocytes from Aiptasia Mutabilis (Cnidaria, anthozoa).A Marino, R. Morabito, G. La Spada, NC Adragna and PK Lauf. Faseb J 2011.

Research Projects

PROTEOMICS OF M-L ANTIGENS MODULATING CATION TRANSPORT
PRINCIPAL INVESTIGATOR
AGENCY: NIH 1 R21 DK064140
(7/1/03-6/30/05).
The major goal of this project is to use new proteomics technology to elucidate the biochemical nature of the M-L antigens that are associated with monvalent cation transport in sheep erythrocytes. This project deals with immunological aspects of surface antigens and membrane transporters.

THIRD SYMPOSIUM ON CELL VOLUME AND SIGNALING
PRINCIPAL INVESTIGATOR
AGENCY: NIH 1R13 DK064886-01
(7/1/03-6/30/04).
The major goal of this project is to manage the Third International Symposium on Cell Volume and Signaling.

ROLE OF ION TRANSPORTERS AND APOPTOSIS IN THE PATHOGENESIS OF HUMAN CATARACT
PRINCIPAL INVESTIGATOR
AGENCY: WRIGHT STATE UNIVERSITY SCHOOL OF MEDICINE
(5/1/03-4/30/04).
This project examines the involvement of membrane transporters in the origin of lens cataract in humans.