Principal Investigator/Program Director (Last, First, Middle): Cowley, Jr., Allen Wilson BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Cowley, Jr., Allen Wilson, Ph.D. Professor and Chairman eRA COMMONS USER NAME acowley EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION Trinity College, Hartford, CT Hahnemann Medical College, Philadelphia, PA Hahnemann Medical College, Philadelphia, PA University of Mississippi DEGREE (if applicable) YEAR(s) B.A. M.S. Ph.D. Postdoctoral 1961 1965 1968 1968 FIELD OF STUDY Economics Physiology Physiology Physiology A. Positions and Honors. Positions and Employment 1969-1974 Assist. Professor of Physiology & Biophysics, Univ. of Mississippi Medical Center, Jackson, MS 1974 Assoc. Prof. of Physiology & Biophysics, Univ. of Mississippi Medical Center, Jackson, MS 1974-1975 Visiting Professor of Physiology, Harvard Medical School 1975-1980 Professor of Physiology & Biophysics, Univ. of Mississippi Medical Center, Jackson, MS 1976-1980 Director of Graduate Studies, Dept. of Physiology & Biophysics, Univ. of Mississippi Medical Center, Jackson, MS 1980-present Professor and Chair, Dept. of Physiology, Medical College of Wisconsin, Milwaukee, WI Honors 1973-78, Established Investigator, American Heart Association (AHA); 1979-83, NIH Study SectionCardiovascular and Renal; 1999-present, Editorial Board, Physiological Reviews; 1999-present, Sr. Editor, Physiological Genomics; Associate Editor, American Journal of Physiology, Heart and Circulation; 1999-04; Associate Editor, American Journal of Physiology: Regulatory, Comp., Integ., 2001-2005; Member, Board of Directors, The Medical College of Wisconsin; 1988-93, Member, Council of the American Physiology Society (APS); 1990-92, Chairman, AHA: Council for High Blood Pressure Research; 1994-95, NASA Life and Microgravity Sciences and Applications Advisory Committee; 1993-97, Member, NHLBI Research Review Committee A/B; 1993, Distinguished Service Award-Medical College of Wisconsin; 1996, Distinguished Achievement Award - AHA; 1996, Starling Distinguished Lectureship of the APS; 1997, President of the APS; 1997, Wiggers Award Recipient, APS; 1997, Novartis Award Recipient, Council for High Blood Pressure Research, AHA; 1998-2002, NHLBI Advisory Council; Doctor Honoris Causa, Semmelweis University of Medicine, Budapest, Hungary; 2001-2005, President of the International Union of Physiological Sciences; 2002, Walter B. Cannon Lectureship, APS; 2004, Distinguished Scientist Award, AHA; 2006, NHLBI Strategic Plan Committee. B. Selected peer-reviewed publications (in chronological order). 1. Cowley AW Jr, Stoll M, Greene AS, Kaldunski ML, Roman RJ, Tonellato PJ, Schork NJ, Jacob HJ. Genetically defined risk of salt-sensitivity within a population of F2 rats from a Brown Norway and Dahl S derived intercross. Physiol Genomics 2:107-115, 2000. 2. Johnson RJ, Gordon KL, Giachilli C, Kurth T, Skelton MM, Cowley AW Jr. Tubulointerstitial injury and loss of nitric oxide synthases parallel the development of hypertension in the Dahl-SS rat. J Hypertension 18:1497-1505, 2000. 3. Stoll M, Cowley AW Jr, Tonellato PJ, Greene AS, Kaldunski ML, Roman RJ, Dumas P, Schork N, Wang Z, Jacob HJ. A genomic-systems biology map for cardiovascular function. Science 294:1723-1726, 2001. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 9 Biographical Sketch Format Page Principal Investigator/Program Director (Last, First, Middle): Cowley, Jr., Allen Wilson 4. Liang M, Yuan B, Rute E, Greene AS, Zou A-P, Soares P, McQuestion G, Slocum GR, Jacob HJ, Cowley AW Jr. Rat renal medullary genes associated with salt-sensitive hypertension identified by chromosomal substitution and cDNA microarray. Phys Genomics 8:139-149, 2002. 5. Makino A, Zou A-P, Cowley AW Jr. Increased renal medullary oxidative stress produces hypertension. Hypertension 39:667-672, 2002. 6. Mori T, Dickhout JG, Cowley AW Jr. Vasopressin stimulates nitric oxide release via Ca2+ signaling in inner medullary collecting duct. Hypertension 39:465-469, 2002. 7. Dickhout JG, Mori T, Cowley AW Jr. Tubulovascular nitric oxide crosstalk: buffering of angiotensin IIinduced medullary vasoconstriction. Circ Res. 91:487-493, 2002. 8. Szentivanyi M Jr, Zou A-P, Mattson DL, Soares P, Moreno C, Roman RJ, Cowley AW Jr. Renal medullary nitric oxide deficit of Dahl S rats enhances hypertensive actions of angiotensin II. Am J Physiol Regul Integr and Comp Physiol. 283:R266-R272, 2002. 9. Mori T, Dickhout JG, Cowley AW Jr. Vasopressin increases intracellular NO concentration via Ca 2+ signaling in inner medullary collecting duct. Hypertension 39 [part 2]:465-469, 2002. 10. Cowley AW Jr. Genomics and homeostasis. Am J Physiol. 284:R611-R627, 2002. 11. Liang M, Yuan B, Rute E, Greene AS, Olivier M, Cowley AW Jr. Insights into Dahl salt-sensitive hypertension revealed by temporal patterns of renal medullary gene expression. Physiol Genomics 12:229237, 2003. 12. Mori T, Cowley AW Jr. Angiotensin II-NAD(P)H oxidase-stimulated superoxide modifies tubulovascular nitric oxide cross-talk in renal outer medulla. Hypertension 42(4):588-593, 2003. 13. Liang M, Briggs AG, Rute E, Greene AS, Cowley AW Jr. Quantitative assessment of the importance of dye switching and biological replication in the cDNA miroarray studies. Physiol Genomics 14:199-207, 2003. 14. Makino A, Skelton MM, Zou A-P, Cowley AW Jr. Increased renal medullary H2O2 leads to hypertension. Hypertension 42:25-30, 2003. 15. Cowley AW Jr, Mori T, Mattson DL, Zou A-P. Role of renal NO production in the regulation of medullary blood flow. Am J Physiol 284:R1355-1369, 2003. 16. Yuan B, Liang M, Yang Z, Rute E, Taylor N, Olivier M, Cowley AW Jr. Gene expression reveals vulnerability to oxidative stress and interstitial fibrosis of renal outer medulla to non-hypertensive elevations of Ang II. Am J Physiol. 284(5):R1219-1230, 2003. 17. Moreno C, Dumas P, Kaldunski ML, Tonellato PJ, Greene AS, Roman RJ, Cheng Q, Wang Z, Jacob HJ, Cowley AW Jr. Genomic map of cardiovascular phenotypes of hypertension in female Dahl S rats. Physiol Genomics 15:243-257, 2003. 18. Mori T, Cowley AW Jr. Role of pressure in angiotensin II-induced renal injury: chronic servo-control of renal perfusion pressure in rats. Hypertension 43:752-759, 2004. 19. Mori T, Cowley AW Jr. Renal oxidative stress in medullary thick ascending limbs produced by elevated NaCl and glucose. Hypertension 43:341-346, 2004. 20. Cowley AW Jr, Roman RJ, Jacob HJ. Application of chromosomal substitution techniques in gene-function discovery. J Physiol. 554:46-55, 2004. 21. Liang M, Cowley AW Jr, Greene AS. High throughput gene expression profiling: a molecular approach to integrative physiology. J Physiol. 554:22-30, 2004. 22. Cowley AW Jr, Liang M, Roman RJ, Greene AS, Jacob HJ. Consomic rat model systems for physiological genomics. Acta Physiol Scand. 181:585-592, 2004. 23. Liang M, Cowley AW Jr, Hessner MJ, Lazar J, Basile DP, Pietrusz JL. Transcriptome analysis and kidney research: toward systems biology. Kidney Int. 67(6):2114-22, 2005. 24. Dwinell MR, Forster HV, Petersen J, Rider A, Kunert MP, Cowley AW Jr, Jacob HJ. Genetic determinants on rat chromosome 6 modulate variation in the hypercapnic ventilatory response using consomic strains. J Appl Physiol. 98(5):1630-8, 2005. 25. Mattson DL, Kunert MP, Roman RJ, Jacob HJ, Cowley AW Jr. Substitution of chromosome 1 ameliorates L-NAME hypertension and renal disease in the fawn-hooded hypertensive rat. Am J Physiol Renal Physiol. 288(5):F1015-22, 2005. 26. Basile DP, Fredrich K, Alausa M, Vio CP, Liang M, Rieder MR, Greene AS, Cowley AW Jr. Identification of persistently altered gene expression in the kidney after functional recovery from ischemic acute renal failure. Am J Physiol Renal Physiol. 288(5):F953-63, 2005. 27. Taylor NE, Cowley AW Jr. Effect of renal medullary H2O2 on salt-induced hypertension and renal injury. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 10 Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): Cowley, Jr., Allen Wilson Am J Physiol Regul Integr Comp Physiol. 289(6):R1573-9, 2005. 28. Taylor NE, Glocka P, Liang M, Cowley AW Jr. NADPH oxidase in the renal medulla causes oxidative stress and contributes to salt-sensitive hypertension in Dahl S rats. Hypertension. Epub 2/27, 2006. 29. Kwitek AE, Jacob HJ, Baker JE, Dwinell MR, Forster HV, Greene AS, Kunert MP, Lombard JH, Mattson DL, Pritchard KA Jr., Roman RJ, Tonellato PJ, Cowley AW Jr. BN phenome: detailed characterization of the cardiovascular, renal and pulmonary systems of the sequenced rat. Physiol Genomics 25:303-313, 2006. 30. Abe M, O’Connor P, Kaldunski M, Liang M, Roman RJ, Cowley AW Jr. Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb. Am J Physio. 291:F350-F357, 2006. 31. Taylor NE, Maier KG, Roman RJ, Cowley AW Jr. NO synthase uncoupling in the kidney of Dahl S rats: Role of dihydrobiopterin. Hypertension 48:1066-1071, 2006. 32. Kunert MP, Drenjancevic-Peric I, Dwinell MR, Lombard JH, Cowley AW Jr, Greene AS, Kwitek AE, Jacob HJ. Consomic strategies to localize genomic regions related to vascular reactivity in the Dahl salt-sensitive rat. Physiol. Genomics 26:218-225, 2006. 33. Cowley AW Jr. The genetic dissection of essential hypertension. Nat Rev Genet. 7(11):829-840, 2006. 34. O’Connor PM, Cowley AW Jr. Vasopressin-induced nitric oxide production in rat inner medullary collecting duct is dependent on V2 receptor activation of the phosphoinositide pathway. Am J Physiol Renal Physiol. 293(2):F526-32, 2007. 35. Mori T, O’Connor PM, Abe M, Cowley AW Jr. Enhanced superoxide production in renal outer medulla of Dahl salt-sensitive rats reduces nitric oxide tubular-vascular cross-talk. Hypertension 49:1336-41, 2007. 36. Michalkiewicz M, Michalkiewicz T, Geurts AM, Roman RJ, Slocum GR, Singer O, Weihrauch D, Greene AS, Kaldunski M, Verma IM, Jacob HJ, Cowley AW Jr. Efficient transgenic rat production by a lentiviral vector. Am J Physiol Heart Circ Physiol. 293(1):H881-94, 2007. C. Research Support Ongoing Research Support R01 HL081091-03 (Cowley) 5/1/06 – 4/30/11 NIH/NHLBI Mechanisms of Hypertension-induced Renal Injury The goal of this grant is to determine the role that pressure plays in provoking pathways of oxidative stress and injury in the renal outer medulla during the development of Angiotensin II + L-NAME-induced hypertension in Sprague Dawley rats. Role: PI U01 HL66579-08 (Jacob) PI 9/30/00 – 7/31/09 NIH/NHLBI Knock-Out Rats for Physiological Genomics The major goals of this project are to develop, phenotype, and distribute 56 consomic strains in the form of reciprocal chromosomal substitutions. Role: Co-Investigator/Component Director P01 HL29587-27 (Cowley) 3/1/98 – 2/28/13 NIH/NHLBI Blood Pressure – Determinants & Controllers The studies in the Program Project Grant focus on the role of the kidney in the long-term control of arterial pressure. Role: PI PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 11 Continuation Format Page Principal Investigator/Program Director (Last, First, Middle): Cowley, Jr., Allen Wilson P01 HL082798-03 (Cowley) 8/1/06 – 6/30/11 NIH/NHLBI Genetic & Physiological Basis of Salt-induced Hypertension The goal of this grant is to determine the genetic and physiological basis of the protection from salt-sensitivity of blood pressure that occurs with substitution of Brown Norway alleles into regions of the Dahl salt-sensitive rat chromosome 13. Role: PI R37-HL036279-20 (Roman) 4/1/05 – 3/31/10 NIH/NHLBI 20-HETE-TGF-beta in Hypertension-Induced Renal Injury The goal of this study is to determine the mechanisms of the impaired relaxation of cerebral and skeletal muscle resistance arteries that occurs when normotensive animals are subjected to an elevated dietary salt intake. Role: Co-Investigator Relevant Completed Support R37 HL49219-13 (Cowley) PI 1/01/01 – 12/31/05 NIH/NHLBI Renal V1 Vasopressin and Hypertension To define the role of vasopressin in the normal regulation of renal medullary blood flow by studying the effect of small physiological changes of vasopressin on pressure flow relationships in the kidney of the V1 and V2 receptors and localize these receptors in microdissected vessels using molecular techniques. Role: PI P50 HL54998-10 (Cowley) PI 2/01/96 – 6/30/06 NIH/NHLBI SCOR-Molecular Genetics of Hypertension To determine the genetic loci and specific genes whose expression results in hypertension and in important phenotypic changes associated with hypertension. Role: PI PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 12 Continuation Format Page