The Targoff Laboratory is a new addition to Columbia University Medical Center and to the Wu Center for Molecular Cardiology. Dr. Targoff’s research interests focus on understanding cardiac morphogenesis: a carefully orchestrated process representing the first organogenesis milestone in developing vertebrate embryos. Establishment of specific molecular and cellular characteristics of the two major cardiac chambers, the ventricle and the atrium, is crucial to formation of a functional heart. Despite the importance of maintaining unique features in chamber-specific cardiomyocytes, the regulatory mechanisms guiding these processes are yet to be uncovered. The strong association of NKX2-5 with human congenital heart disease in both chambers and our studies revealing the differential effects of nkx genes on ventricular and atrial cell number in zebrafish prompted our interest in the role of Nkx genes in chamber identity. By exploiting the experimental benefits of the zebrafish model, we have shown that ventricular cardiomyocytes transdifferentiate into atrial cardiomyocytes in the absence of nkx gene function, highlighting the malleable nature of differentiated myocardium. We propose that the newly revealed functions of Nkx genes in preserving chamber specific traits will help to explain the molecular, cellular, and electrophysiological phenotypes in models of Nkx2-5 deficiency. In the long-term, these studies have potential to shed light on etiologies of fetal and neonatal cardiac pathology and to drive innovations in regenerative medicine.
Dr. Targoff has also been instrumental in setting up the first Zebrafish Facility at Columbia University. The transparent zebrafish embryo allows for microscopic observation of the developing heart throughout embryogenesis. Expression of reporter transgenes allows in vivo identification of individual fluorescent cardiomyocytes, tracking of cell movements, and evaluation of cell shape changes. Understanding the molecular and cellular functions of cardiac transcriptional hierarchy is greatly benefited by an experimental system with the capacity for detailed phenotypic characterization in live embryos.
The Columbia University Zebrafish Facility is located on the 4th floor of the Black Building and houses 21 aquatic racks designed and constructed by Aquaneering, Inc. A Zebrafish Procedure Room has been created in close proximity to the Zebrafish Facility and is equipped with dissecting fluorescent microscopes, microinjectors, and transplantation rigs. The Facility currently maintains 50 different strains of wild-type, mutant, and transgenic fish for use by the Targoff Lab. Additional lines will be added as new investigators utilize these Zebrafish resources.
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