An important motivation for our research is to understand the basis for congenital heart disease. Congenital heart disease affects 1 out of 100 children, and is the leading non-infectious cause of death in the first year of life. And yet we know very little about what causes these defects, except that they arise from abnormal heart formation. We use mouse models, and human induced pluripotent cell (iPS cell) models of disease, to unravel the molecular pathways that become tangled, resulting in congenital heart defects. From the allocation and patterning of cardiac precursors, to the function of transcription factors and chromatin-level regulators, much of our work is aimed at understanding congenital heart defects. We hope to be able to bring clinically-relevant insights into congenital heart disease, and some fundamental knowledge that will help understand their origin.

Representative Papers:

  • Chromatin remodeling complex dosage modulates transcription factor function in heart development. Takeuchi J.K., Lou X., Alexander J.M., Sugizaki H., Delgado-Olguin P., Holloway A.K., Mori A.D., Wylie J.N., Munson C., Zhu Y., Zhou Y.Q., Yeh R.F., Henkelman R.M., Harvey R.P., Metzger D., Chambon P., Stainier D.Y., Pollard K.S., Scott I.C., & Bruneau B.G. (2011) Nature Communications 2011,2:187 (PMC: Open; PMC3096875)

  • Reptilian heart development and the molecular basis of cardiac chamber evolution. Koshiba-Takeuchi K.T., Mori A.D., Kaynak B.L., Cebra-Thomas J., Sukonnik T., Georges R.O., Latham S., Beck L., Henkelman R.M., Black B.L., Olson E.N., Wade J., Takeuchi J.K., Nemer M., Gilbert S.F. & Bruneau B.G. (2009) Nature 461:95-98 (PMC2753965).

  • Modeling human TBX5 haploinsufficiency predicts regulatory networks for congenital heart disease. Kathiriya I.K., Rao K.S., Iacono G., Devine W.P., Blair A.P., Hota S.K., Lai M.H., Garay B.I., Thomas R., Gong H.Z., Wasson L.K., Goyal P., Sukonnik T., Hu K.M., Akgun G.A., Bernard L.D., Akerberg B.N., Gu F., Li K., Speir M.L., Haeussler M., Pu W.T., Stuart J.M., Seidman C.E., Seidman J.G., Heyn H., Bruneau B.G. Developmental Cell 2020 accepted.

  • Modeling congenital heart disease: lessons from mice, hPSC-based models, and organoids. Rao KS, Kameswaran V, Bruneau BG. Genes Dev. 2022 Jun 1;36(11-12):652-663.