DPLM Faculty Profiles — Dr. Kakoki

Masao Kakoki

Masao Kakoki, MD, PhD

Associate Professor

Office: 919-966-6912

E-mail: mkakoki@med.unc.edu

Research Interests

My research aims at prevention and treatment of cardiovascular diseases and focuses on the identification of genes that confer susceptibility or resistance to the diseases with the use of genetically engineered mice. Very recently Dr. Smithies and I developed a new method for altering gene expression by modifying 3’ untranslated regions in mice (Publication 23), which enables fine-tuned modification of gene expression. I am now analyzing the phenotypes of several mouse models generated with this method.

Selected Publications

1. Hayakawa H, Hirata Y, Suzuki E, Kakoki M, Kikuchi K, Nagano T, Hirobe M, Omata M. Endothelium-derived relaxing factors in the kidney of spontaneously hypertensive rats. Life Sci. 1995;56:L401-8.

2. Matsumoto A, Ogura K, Hirata Y, Kakoki M, Watanabe F, Takenaka K, Shiratori Y, Momomura S, Omata M. Increased nitric oxide in the exhaled air of patients with decompensated liver cirrhosis. Ann Intern Med. 1995;123:110-3.

3. Hirata Y, Hayakawa H, Kakoki M, Tojo A, Suzuki E, Kimura K, Goto A, Kikuchi K, Nagano T, Hirobe M, Omata M. Nitric oxide release from kidneys of hypertensive rats treated with imidapril. Hypertension. 1996;27:672-8.

4. Nakamura Y, Kakoki M, Yamakado M. The effect of age on glucose tolerance and plasma insulin level in hypertensive and normotensive subjects. Hypertens Res. 1996;19:S23-6.

5. Hirata Y, Hayakawa H, Kakoki M, Tojo A, Suzuki E, Nagata D, Kimura K, Goto A, Kikuchi K, Nagano T, Hirobe M, Omata M. Receptor subtype for vasopressin-induced release of nitric oxide from rat kidney. Hypertension. 1997;29:58-64.

6. Hayakawa H, Hirata Y, Kakoki M, Suzuki Y, Nishimatsu H, Nagata D, Suzuki E, Kikuchi K, Nagano T, Kangawa K, Matsuo H, Sugimoto T, Omata M. Role of nitric oxide-cGMP pathway in adrenomedullin-induced vasodilation in the rat. Hypertension. 1999;33:689-93.

7. Kakoki M, Matsumoto A, Nagata D, Kobayakawa N, Kimura K, Momomura S, Hirata Y. Analysis of nitric oxide in the exhaled air of patients with chronic glomerulonephritis. Clin Nephrol. 1999;52:83-90.

8. Kakoki M, Hirata Y, Hayakawa H, Tojo A, Nagata D, Suzuki E, Kimura K, Goto A, Kikuchi K, Nagano T, Omata M. Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney. Circulation. 1999;99:1242-8.

9. Kakoki M, Hirata Y, Hayakawa H, Nishimatsu H, Suzuki Y, Nagata D, Suzuki E, Kikuchi K, Nagano T, Omata M. Effects of vasodilatory beta-adrenoceptor antagonists on endothelium-derived nitric oxide release in rat kidney. Hypertension. 1999;33:467-71.

10. Matsumoto A, Hirata Y, Kakoki M, Nagata D, Momomura S, Sugimoto T, Tagawa H, Omata M. Increased excretion of nitric oxide in exhaled air of patients with chronic renal failure. Clin Sci (Lond). 1999;96:67-74.

11. Nagata D, Hirata Y, Suzuki E, Kakoki M, Hayakawa H, Goto A, Ishimitsu T, Minamino N, Ono Y, Kangawa K, Matsuo H, Omata M. Hypoxia-induced adrenomedullin production in the kidney. Kidney Int. 1999;55:1259-67.

12.Suzuki E, Nagata D, Kakoki M, Hayakawa H, Goto A, Omata M, Hirata Y. Molecular mechanisms of endothelin-1-induced cell-cycle progression: involvement of extracellular signal-regulated kinase, protein kinase C, and phosphatidylinositol 3-kinase at distinct points. Circ Res. 1999;84:611-9.

13. Kakoki M, Hirata Y, Hayakawa H, Suzuki E, Nagata D, Nishimatsu H, Kimura K, Goto A, Omata M. Effects of vasodilatory antihypertensive agents on endothelial dysfunction in rats with ischemic acute renal failure. Hypertens Res. 2000;23:527-33.

14. Kakoki M, Hirata Y, Hayakawa H, Suzuki E, Nagata D, Tojo A, Nishimatsu H, Nakanishi N, Hattori Y, Kikuchi K, Nagano T, Omata M. Effects of tetrahydrobiopterin on endothelial dysfunction in rats with ischemic acute renal failure. J Am Soc Nephrol. 2000;11:301-9.

15. Nagata D, Suzuki E, Nishimatsu H, Yoshizumi M, Mano T, Walsh K, Sata M, Kakoki M, Goto A, Omata M, Hirata Y. Cyclin A downregulation and p21(cip1) upregulation correlate with GATA-6-induced growth arrest in glomerular mesangial cells. Circ Res. 2000;87:699-704.

16. Sata M, Kakoki M, Nagata D, Nishimatsu H, Suzuki E, Aoyagi T, Sugiura S, Kojima H, Nagano T, Kangawa K, Matsuo H, Omata M, Nagai R, Hirata Y. Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cyclic GMP-independent mechanism. Hypertension. 2000;36:83-8.

17. Suzuki E, Nagata D, Yoshizumi M, Kakoki M, Goto A, Omata M, Hirata Y. Reentry into the cell cycle of contact-inhibited vascular endothelial cells by a phosphatase inhibitor. Possible involvement of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. J Biol Chem. 2000;275:3637-44.

18. Kakoki M, Zou AP, Mattson DL. The influence of nitric oxide synthase 1 on blood flow and interstitial nitric oxide in the kidney. Am J Physiol Regul Integr Comp Physiol. 2001;281:R91-7.

19. Shindo T, Kurihara Y, Nishimatsu H, Moriyama N, Kakoki M, Wang Y, Imai Y, Ebihara A, Kuwaki T, Ju KH, Minamino N, Kangawa K, Ishikawa T, Fukuda M, Akimoto Y, Kawakami H, Imai T, Morita H, Yazaki Y, Nagai R, Hirata Y, Kurihara H. Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene. Circulation. 2001;104:1964-71.

20. Kakoki M, Wang W, Mattson DL. Cationic amino acid transport in the renal medulla and blood pressure regulation. Hypertension. 2002;39:287-92.

21. Nishimatsu H, Hirata Y, Shindo T, Kurihara H, Kakoki M, Nagata D, Hayakawa H, Satonaka H, Sata M, Tojo A, Suzuki E, Kangawa K, Matsuo H, Kitamura T, Nagai R. Role of endogenous adrenomedullin in the regulation of vascular tone and ischemic renal injury: studies on transgenic/knockout mice of adrenomedullin gene. Circ Res. 2002;90:657-63.

22. Nishimatsu H, Hirata Y, Shindo T, Kurihara H, Suzuki E, Sata M, Satonaka H, Takeda R, Nagata D, Kakoki M, Hayakawa H, Kangawa K, Matsuo H, Kitamura T, Nagai R. Endothelial responses of the aorta from adrenomedullin transgenic mice and knockout mice. Hypertens Res. 2003;26 S79-84.

23. Kakoki M, Tsai YS, Kim HS, Hatada S, Ciavatta DJ, Takahashi N, Arnold LW, Maeda N, Smithies O. Altering the expression in mice of genes by modifying their 3' regions. Dev Cell. 2004;6:597-606.

24. Kakoki M, Kim HS, Arendshorst WJ, Mattson DL. L-Arginine Uptake Affects Nitric Oxide Production and Blood Flow in the Renal Medulla. Am J Physiol Regul Integr Comp Physiol. 2004.

25. Kakoki M, Takahashi N, Jennette JC, Smithies O. Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor. Proc Natl Acad Sci U S A. 2004;101:13302-5.