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/renal diseases and focuses on the identification of genes that confer susceptibility or resistance to the diseases with the use of genetically engineered mice. In 2004, Dr. Smithies and I developed a new method for altering gene expression by modifying 3' untranslated regions in mice (Selected Publication 10), 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. Bai X, Lenhart KC, Bird KE, Suen AA, Rojas M, Kakoki M, Li F, Smithies O, Mack CP, Taylor JM. The smooth muscle-selective RhoGAP GRAF3 is a critical regulator of vascular tone and hypertension. Nat Commun. 2013;4:2910. doi: 10.1038/ncomms3910.

2. Kakoki M, Pochynyuk OM, Hathaway CM, Tomita H, Hagaman JR, Kim HS, Zaika OL, Mamenko M, Kayashima Y, Matsuki K, Hiller S, Li F, Xu L, Grant R, Bertorello AM, Smithies O. Primary aldosteronism and impaired natriuresis in mice underexpressing TGFβ1. Proc Natl Acad Sci U S A. 2013; 110(14):5600-5.

3. Vashistha H, Singhal PC, Malhotra A, Husain M, Mathieson P, Saleem MA, Kuriakose C, Seshan S, Wilk A, Delvalle L, Peruzzi F, Giorgio M, Pelicci PG, Smithies O, Kim HS, Kakoki M, Reiss K, Meggs LG. Null mutations at the p66 and bradykinin 2 receptor loci induce divergent phenotypes in the diabetic kidney. Am J Physiol Renal Physiol. 2012; 303:F1629-40.

4. Tomita, H., Sanford, R.B., Smithies, O., Kakoki, M. The kallikrein-kinin system in diabetic nephropathy. Kidney Int. 2012; 81:733-44.

5. Kayashima, Y., Smithies, O., Kakoki, M. The kallikrein-kinin system and oxidative stress. Curr. Opin. Nephrol. Hypertens. 2012;21:92-6.

6. Kakoki, M., Sullivan, K.A., Backus, C., Hayes, J.M., Oh, S.S., Hua, K., Gasim, A.M., Tomita, H., Grant, R., Nossov, S.B., Kim, H.S., Jennette, J.C., Feldman, E.L., Smithies, O. Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice. Proc. Natl. Acad. Sci. U. S. A. 2010;107:10190-5.

7. Wende, A.R., Soto, J., Olsen, C.D., Pires, K.M., Schell, J.C., Larrieu-Lahargue, F., Litwin, S.E., Kakoki, M., Takahashi, N., Smithies, O., Abel, E.D. Loss of bradykinin signaling does not accelerate the development of cardiac dysfunction in type 1 diabetic akita mice. Endocrinology 2010;151:3536-3542.

8. Brosius, F.C.,3rd, Alpers, C.E., Bottinger, E.P., Breyer, M.D., Coffman, T.M., Gurley, S.B., Harris, R.C., Kakoki, M., Kretzler, M., Leiter, E.H., Levi, M., McIndoe, R.A., Sharma, K., Smithies, O., Susztak, K., Takahashi, N., Takahashi, T. Mouse models of diabetic nephropathy. J. Am. Soc. Nephrol. 2009;20:2503-2512.

9. Kakoki, M., and Smithies, O. The kallikrein-kinin system in health and in diseases of the kidney. Kidney Int. 2009;75:1019-1030.

10. Kakoki, M., Tsai, Y.S., Kim, H.S., Hatada, S., Ciavatta, D.J., Takahashi, N., Arnold, L.W., Maeda, N., Smithies, O. Altering the expression in mice of genes by modifying their 3' regions. Dev. Cell. 2004;6:597-606.