The long-term goal is to understand the function and regulation of genes that are involved in heart development and to elucidate the molecular basis of cardiac differentiation, morpho-genesis and function. Particular emphasis will be placed on the role of the homeobox gene, tinman, during these processes in Drosophila. Drosophila cardiogenesis has become an excellent model for studying the genetic mechanisms that determine the initial phases of heart development in vertebrates, and for finding crucial factors involved in these processes. It is the first system in which the gene network responsible for specifying and positioning the cardiac mesoderm, the tissue that will form the heart, has been characterized in significant detail. As a result, remarkably similarities in molecular mechanisms have been discovered between drosophila and vertebrate heart development, strongly supporting an evolutionary conservation of heart development between insects (Drosophila) and vertebrate. Because of tinman's principal role in heart development, we plan to further elucidate its function and regulation (Aim 1). In a molecular screen, we further propose to identify transacting factors that are necessary for cardiac tinman expression, which is likely to yield new players in heart development (Aim 2), and in addition, may lead to new parallel mechanisms in vertebrate cardiogenesis. In a genetic screen, we further plan to identify new gene functions that are in control of and participate during cardiac differentiation and physiological function (Aim 3). We believe that the proposed research will again serve as a prototype for studying the genetic basis of cardiac differentiation, which already has helped (eg. Schott et al., 1998) and will continue to help to understand the molecular basis of congenital heart disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Wang, Lan-Hsiang
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
Zip Code
Blice-Baum, Anna C; Guida, Maria Clara; Hartley, Paul S et al. (2018) As time flies by: Investigating cardiac aging in the short-lived Drosophila model. Biochim Biophys Acta Mol Basis Dis :
Walls, Stanley M; Cammarato, Anthony; Chatfield, Dale A et al. (2018) Ceramide-Protein Interactions Modulate Ceramide-Associated Lipotoxic Cardiomyopathy. Cell Rep 22:2702-2715
Zanon, Alessandra; Kalvakuri, Sreehari; Rakovic, Aleksandar et al. (2017) SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila. Hum Mol Genet 26:2412-2425
Sessions, Ayla O; Kaushik, Gaurav; Parker, Sarah et al. (2017) Extracellular matrix downregulation in the Drosophila heart preserves contractile function and improves lifespan. Matrix Biol 62:15-27
Diop, Soda Balla; Birse, Ryan T; Bodmer, Rolf (2017) High Fat Diet Feeding and High Throughput Triacylglyceride Assay in Drosophila Melanogaster. J Vis Exp :
Zarndt, Rachel; Walls, Stanley M; Ocorr, Karen et al. (2017) Reduced Cardiac Calcineurin Expression Mimics Long-Term Hypoxia-Induced Heart Defects in Drosophila. Circ Cardiovasc Genet 10:
Blice-Baum, Anna C; Zambon, Alexander C; Kaushik, Gaurav et al. (2017) Modest overexpression of FOXO maintains cardiac proteostasis and ameliorates age-associated functional decline. Aging Cell 16:93-103
Gan, Zhuohui; Powell, Frank L; Zambon, Alexander C et al. (2017) Transcriptomic analysis identifies a role of PI3K-Akt signalling in the responses of skeletal muscle to acute hypoxia in vivo. J Physiol 595:5797-5813
Del Álamo, Juan C; Lemons, Derek; Serrano, Ricardo et al. (2016) High throughput physiological screening of iPSC-derived cardiomyocytes for drug development. Biochim Biophys Acta 1863:1717-27
Trujillo, Gloriana V; Nodal, Dalea H; Lovato, Candice V et al. (2016) The canonical Wingless signaling pathway is required but not sufficient for inflow tract formation in the Drosophila melanogaster heart. Dev Biol 413:16-25

Showing the most recent 10 out of 58 publications