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Hideko Kasahara, M.D., Ph.D.

Associate Professor

Hideko Kasahara

Hideko Kasahara

(352) 846-1503

Office: MSB M540B

hkasahar@ufl.edu

PubMed Listing

Biosketch

Research:

Our current research interest is to understand the function of Nkx2.5, an evolutionarily conserved NK2 class of homeobox transcription factor in mature cardiomyocytes.  Within the genomic analysis of cardiovascular diseases, mutations of NKX2.5 (capitals are used for human Nkx2.5) have emerged as a fascinating story both because of the roles this transcription factor plays in formation of the developing heart, as well as in maintenance of the normal heart after birth and through to adulthood.  We are particularly interested in a cardiac disorder in adults:  progressive AV block and left verntricular dysfunction caused by NKX2.5 mutations.  However, the current understanding of NKX2.5’s function is very limited in explaining how the molecular mechanisms of NKX2.5 mutations cause congenital heart disease.

Education:

1985: M.D. Nagoya University Medical School, Japan (Medicine)
1994: Ph.D. Nagoya University Medical School, Japan (Cardiology, Cell Biology)
1991-1994: National Institute for Physiological Sciences, Japan (Cell Biology)

Postdoctoral Training:

1994-1997: Postdoctoral Fellow,

Department of Internal Medicine-Cardiology,

Cardiovascular Research Center, University of Michigan,

Ann Arbor, MI

1997-1998: Postdoctoral Fellow, Cardiovascular Division,

Beth Israel Deaconess Medical Center / Harvard Medical School,

Boston, MA

Academic Appointments:

1998-2001: Instructor of Medicine, Harvard Medical School / Beth Israel Deaconess Medical Center
2002-2009 Assistant Professor in the Department of Physiology and Functional Genomics,

University of Florida College of Medicine

2009- Associate Professor in the Department of Physiology and Functional Genomics,

University of Florida College of Medicine

Awards and Honors:

1995-1996: Post-Doctoral Research Fellowship (AHA-Michigan), 15F956
1996-1997: Post-Doctoral Research Fellowship (AHA-Michigan), 05RF967
1998-2000: Post-Doctoral Research Fellowship (AHA-New England), 9820043T
2000: Melvin L.Marcus Young Investigator Award (first prize), American Heart Association 73rd Scientific Sessions
2006: Abstract Travel Award, American Heart Association, Council on Basic Cardiovascular Sciences

Publications:

  1. Ashraf H., Pradhan L., Chang E.I., Terada R., Ryan N.J., Briggs L.E., Chowdhury R., Zárate M.A., Sugi Y., Nam H-J., Benson D.W., Anderson R. H., Kasahara H.: A mouse model of human congenital heart disease: High incidence of diverse cardiac anomalies and ventricular noncompaction produced by heterozygous Nkx2-5 homeodomain missense mutation. Circ Cardiovasc Genet. 2014, in press.
  2. Lee K.Y., Li M., Manchanda M., Batra R., Charizanis K., Mohan A., Warren S.A., Chamberlain C.M., Finn D., Hong H., Ashraf H., Kasahara H., Ranum L.P., Swanson M.S.: Compound loss of muscleblind-like function in myotonic dystrophy. EMBO Mol Med. 2013:5:1887-1900. Abstract (Pubmed)
  3. Warren S.A., Briggs L.E., Zeng H., Chuang J., Chang E.I., Terada R., Li M., Swanson M.S., Lecker S.H., Willis M.S., Spinale F.G., Maupine-Furlowe J., McMullen J.R., Moss, R.L., Kasahara H.: Myosin light chain phosphorylation is critical for adaptation to cardiac stress. Circulation 2012: 126(22):2575-2588. Abstract (Pubmed)
  4. Pradhan L., Genis C., Scone P., Weinberg E.O., Kasahara H., Nam H-J.: Crystal structure of the human NKX2.5 homeodomain in complex with DNA target. Biochemistry. 2012: 51(32):6312-6319. Abstract (Pubmed)
  5. Miyazaki, Y., Ikeda Y., Shiraishi, K., Fujimoto S., Aoyama, H., Yoshimura, K., Inui M., Hoshijima, M., Kasahara H., Aoki H., Matsuzaki, M.: Heart failure-inducible gene therapy targeting protein phosphatase 1beta prevents progressive left ventricular remodeling. PLoS One. 2012: 7(4):e35875. Abstract (Pubmed)
  6. Sheikh, F., Ouyang, K., Campbell, S.G., Lyon, R.C., Chuang, J., Fitzsimons, D., Tangney, J., Hidalgo, C.G., Chung, C.S., Cheng, H., Dalton, N.D., Gu, Y., Kasahara, H., Ghassemian, M., Omens, J.H., Peterson, K.L., Granzier, H.L., Moss, R.L., McCulloch, A.D., Chen, J.: Integrative mouse and computational models link altered myosin kinetics to early events in cardiac disease. J.Clin.Invest. 2012:122:1209-1221. Abstract (Pubmed)
  7. Cole-Jeffrey, C.T., Terada R., Neth M.R., Wessels A., Kasahara H.: Progressive anatomical closure of foramen ovale in normal neonatal mouse hearts. Anat. Rec. 2012:295:764-768. PMID: 22354769.
  8. Carcamo W.C., Satoh M., Kasahara H. Terada N., Hamazaki T., Chan J.Y., Yao B., Tamayo S., Covini G., von Mühlen C.A., Chan E.K: Induction of Cytoplasmic Rods and Rings Structures by Inhibition of the CTP and GTP Synthetic Pathway in Mammalian Cells. PLoS One. 2011;6(12):e29690. Abstract (Pubmed)
  9. Warren S.A., Terada R., Briggs L.E., Cole-Jeffrey C.T., Chien W., Seki T., Weinberg, E.O.. Yang, T.P., Chin M.T., Bungert J., Kasahara H.: Differential role of Nkx2-5 in activation of the ANF gene in developing vs. failing heart. Mol Cell Biol. 2011:31: 4633-4645. Abstract (Pubmed)
  10. Terada R., Warren S.A., Lu J.T., Wessels, A., Chien K.R., Kasahara H.: Ablation of Nkx2-5 beginning at mid-embryonic stage results in premature lethality and cardiac malformation. Cardiovasc Res. 2011: 91:289-299. Abstract (Pubmed)
  11. Kirabo A., Oh S.P, Kasahara H., Wagner KU., Sayeski P.P.: Vascular smooth muscle Jak2 deletion prevents angiotensin II-mediated neointima formation following injury in mice. J.Mol.Cell.Cardiol. 2011:50:1026-1034. Abstract (Pubmed)
  12. Kirabo A., Kears P.N., Jarajapu Y.P., Sasser J.M., Oh S.P., Grant M.B., Kasahara H., Cardounel A.J., Baylis C., Wagner K-U., Sayeski P.P.: Vascular smooth muscle Jak2 mediates Angiotensin II-induced hypertension via increased levels of reactive oxygen species. Cardiovasc Res. 2011: 91: 171-179. Abstract (Pubmed)
  13. Takeda M., Briggs L.E., Wakimoto H., Marks M.H., Warren S.A., Lu J.T., Weinberg, E.O., Robertson. K.D., Chien K.R., Kasahara H.: Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation. Lab. Invest. 2009. In press. Abstract (Pubmed)
  14. Genis C., Scone P., Kasahara H., Nam H-J.: Crystallization and preliminary X-ray analysis of NKX2.5 homeoprotein in complex with DNA. Acta Crystallogr SectF Struct Biol Cryst Commun. 2008:F64:1079-1082. Abstract (Pubmed)
  15. Briggs L.E., Takeda M, Cuadra A.E., Wakimoto H., Marks M.H., Seki T., Oh SP., Lu J.T., Sumners C., Raizada, M.K., Horikoshi N., Weinberg, E.O.,Yasui K., Ikeda Y., Chien K.R., Kasahara H.: Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects. Circ. Res. 2008:103:580-590. Abstract (Pubmed)
  16. Chan JY, Takeda M, Briggs LM, Graham ML, Lu JT, Horikoshi N, Weinberg EO, Aoki H, Sato N, Chien KR, and Kasahara H. Identification of cardiac-specific myosin light chain kinase. Circ. Res. 2008:102:571-580. Abstract (Pubmed)
  17. Andino LM, Takeda M, Kasahara H, Jakymiw A, Byrne BJ and Lewin AS. AAV-mediated knockdown of phospholamban leads to improved contractility and calcium handing in cardiomyocytes. J. Gene Med. 2008:10:132-142. Abstract (Pubmed)
  18. Singh AM, Li F-Q, Hamazaki T, Kasahara H, Takemaru K, and Terada N. Chibby, and antagonist of the Wnt/beta-catenin pathway, facilitates cardiomyocyte differentiation of murine embryonic stem cells. Circulation. 2007:115:617-626. Abstract (Pubmed)
  19. Tang YL, Tang Y Zhang YC, Agarwal, A, Kasahara H, Qian K, Shen L and Phillips MI. A hypoxia-inducible vigilant vector system for activating therapeutic genes in ischemia. Gene Ther. 2005:15:1163-1170. Abstract (Pubmed)
  20. Kajstura J, Rota M, Whang B, Cascapera S, Hosoda T, Bearzi C, Nurzynska D, Kasahara H, Zias E, Bonafe M, Nadal-Ginard B, Torella D, Nascimbene A, Quaini F, Urbanek K, Leri A, Anversa P. Bone Marrow Cells Differentiate in Cardiac Cell Lineages After Infarction Independently of Cell Fusion. Circ Res. 2005:96:127-137. Abstract (Pubmed)
  21. Kasahara H. Monogenic causes of heart failure – familial dilated cardiomyopathy (DCM). IN: Raizada, M.K., Paton, J.F.R., Kasparov, S., and Katovich, M.J. (ed). Contemporary Cardiology: Cardiovascular Genomics. Humana Press, Inc., Totowa, NJ, 2005: 115-134.
  22. Kasahara H, and Aoki H. Gene silencing using adenoviral RNAi in vascular smooth muscle cells and cardiomyocytes. IN: Sun Z. (ed) Methods in Molecular Medicine vol. 112: Molecular Cardiology: Methods and Protocols. Humana Press, Inc., Totowa, NJ, 2005:155-172.
  23. Kasahara H and Benson DW. Biochemical analyses of eight NKX2.5 homeodomain missense mutations causing atrioventricular block and cardiac anomalies. Cardiovasc Res. 2004:64:40-51. Abstract (Pubmed)
  24. Ueyama T, Kasahara H, Ishiwata T, Nie Q and Izumo S. Myocardin expression is regulated by Nkx2.5 and its function is required for cardiomyogenesis. Mol.Cell Biol. 2003:23:9222-9232. Abstract (Pubmed)
  25. Wakimoto H, Kasahara H, Magurire CT, Moskowitz PG, Izumo S and Berul CI. Cardiac electrophysiological phenotypes in postnatal expression of Nkx2.5 transgenic mice. Genesis 2003:37:144-150. Abstract (Pubmed)
  26. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B and Anversa P. Adult Cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003:114:763-776. Abstract (Pubmed)
  27. Sato N, Kawakami T, Nakayama A, Suzuki H, Kayukawa K, Kasahara H and Obinta T. A novel variant of cardiac myosin-binding protein-C (MyBP-C/C-protein) that is unable to assemble into sarcomeres is expressed in aged mouse atrium. Mol. Biol. Cell. 2003:14:3180-3191. Abstract (Pubmed)
  28. Ueyama T, Kasahara H, Ishiwata T, Yamazaki N and Izumo S. Csm, a cardiac specific isoform of the RNA helicase Mov10l1, is regulated by Nkx2.5 in embryonic heart. J. Biol. Chem. 2003:278:28750-28757. Abstract (Pubmed)
  29. Kasahara H, Ueyama T, Wakimoto H, Liu MK, Magurire CT, Converso KL, Kang, PM, Manning WJ, Lawitts, J, Paul DL, Berul CI and Izumo S. Nkx2.5 homeoprotein regulates expression of gap junction protein connexin 43 and sarcomere organization in postnatal cardiomyocytes. J. Mol. Cell. Cardiol. 2003:35:243-256. Abstract (Pubmed)
  30. Muller JG, Thompson JT, Edmonson, AM, Rackley MS, Kasahara H, Izumo S, McQuinn TC, Menick DR, O’Brien TX.  Differential Regulation of the cardiac sodium calcium exchanger promoter in adult and neonatal cardiomyocytes by Nkx2.5 and serum response factor.  J. Mol. Cell. Cardiology 2002:34:807-821 Abstract (Pubmed)
  31. Wakimoto H, Kasahara H, Macgurire CT, Izumo S, Berul CI.  Developmentally modulated cardiac conduction failure in transgenic mice with fetal or postnatal overexpression of DNA nonbinding mutant Nkx2.5.   J. Cardiovasc. Electrophysiol .  2002:13:682-688   Abstract (Pubmed)
  32. Thomas PS, Kasahara H, Edmonson AM, Izumo S, Yacoub MH, Barton PJ, Gourdie RG. Elevated expression of Nkx-2.5 in developing myocardial conduction cells. Anat Rec. 2001 Jul 1;263(3):307-13. Abstract (PubMed)
  33. Kasahara H, Wakimoto H, Liu M, Maguire CT, Converso KL, Shioi T, Huang WY, Manning WJ, Paul D, Lawitts J, Berul CI, Izumo S. Progressive atrioventricular conduction defects and heart failure in mice expressing a mutant Csx/Nkx2.5 homeoprotein.J Clin Invest. 2001 Jul;108(2):189-201. Abstract (PubMed)
  34. Kasahara H, Usheva A, Ueyama T, Aoki H, Horikoshi N, Izumo S. Characterization of homo- and heterodimerization of cardiac Csx/Nkx2.5 homeoprotein. J Biol Chem. 2001 Feb 16;276(7):4570-80. Abstract (PubMed)
  35. Guo L, Lynch J, Nakamura K, Fliegel L, Kasahara H, Izumo S, Komuro I, Agellon LB, Michalak M. COUP-TF1 antagonizes Nkx2.5-mediated activation of the calreticulin gene during cardiac development. J Biol Chem. 2001 Jan 26;276(4):2797-801. Abstract (PubMed)
  36. Kasahara H, Lee B, Schott JJ, Benson DW, Seidman JG, Seidman CE, Izumo S. Loss of function and inhibitory effects of human CSX/NKX2.5 homeoprotein mutations associated with congenital heart disease. J Clin Invest. 2000 Jul;106(2):299-308. Abstract (PubMed)
  37. Kasahara H, Izumo S. Identification of the in vivo casein kinase II phosphorylation site within the homeodomain of the cardiac tisue-specifying homeobox gene product Csx/Nkx2.5. Mol Cell Biol . 1999 Jan;19(1):526-36. Abstract (PubMed)
  38. Tanaka M, Kasahara H, Bartunkova S, Schinke M, Komuro I, Inagaki H, Lee Y, Lyons GE, Izumo S. Vertebrate homologs of tinman and bagpipe: roles of the homeobox genes in cardiovascular development. Dev Genet. 1998;22(3):239-49. Abstract (PubMed)
  39. Lee Y, Shioi T, Kasahara H, Jobe SM, Wiese RJ, Markham BE, Izumo S. The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression. Mol Cell Biol . 1998 Jun;18(6):3120-9. Abstract (PubMed)
  40. Kasahara H, Bartunkova S, Schinke M, Tanaka M, Izumo S. Cardiac and extracardiac expression of Csx/Nkx2.5 homeodomain protein. Circ Res. 1998 May 18;82(9):936-46. Abstract (PubMed)
  41. Takeuchi K, Sato N, Kasahara H, Funayama N, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members. J Cell Biol. 1994 Jun;125(6):1371-84. Abstract (PubMed)
  42. Kasahara H, Itoh M, Sugiyama T, Kido N, Hayashi H, Saito H, Tsukita S, Kato N. Autoimmune myocarditis induced in mice by cardiac C-protein. Cloning of complementary DNA encoding murine cardiac C-protein and partial characterization of the antigenic peptides. J Clin Invest . 1994 Sep;94(3):1026-36. Abstract (PubMed)
  43. Uchida K, Nakata S, Iwase H, Yamamoto H, Kasahara H, Konagaya T. [Imaging diagnosis of ruptured site in hepatocellular carcinoma] Nippon Shokakibyo Gakkai Zasshi. 1989 Jun;86(6):1287-91. Japanese. Abstract (PubMed)