Anthony Azakie, M.D.
	Transcriptional Regulation of Cardiac Growth and Development
	Email: azakiet@surgery.ucsf.edu Websites:
Selected Publications | Complete Publications

Our lab studies the regulation of cardiac-specific gene expression during embryogenesis, and maladaptive myocardial responses to biomechanical or neurohormonal stress. We use chick, murine, ovine, and human systems to determine the role of cardiac transcription factors and promoter elements in: (1) cardiac myocyte specification, (2) regulation of cardiac gene expression during development and pathologic conditions, and (3) the induction of the fetal cardiac program during maladaptive hypertrophy and heart failure. We have focused on the Transcriptional Enhancer Factor-1 (TEF-1) multigene family of transcription factors and specifically DTEF-1, a cardiac enriched family member that is expressed early in development. DTEF-1 activates cardiac promoters and has been implicated in the regulation of pathologic hypertrophy and heart failure. It is believed to be an early marker of the cardiac phenotype. We also focus on identifying novel cardiac transcription factors involved in determination of the cardiac muscle phenotype.

Molecular and biochemical experiments are aimed at identifying transcriptional control mechanisms. Gain and loss of function experiments, in vivo, are also performed by manipulating these genes in both space and time using inducible Cre-lox transgenic mouse models. We also perform complex fetal cardiac surgery to generate novel ovine models of heart failure and congenital heart disease. Finally, we analyze the genomic complement and differential gene expression patterns in cardiac surgical specimens to identify potential mechanisms of human disease.

Our long term goal is to identify the mechanisms for the formation of myocardium and to characterize clinically relevant maladaptive responses of cardiac muscle. This information could be used to (1) devise genetic approaches to bioengineer cardiac myoblasts for cell transplantation in heart failure, (2) devise pharmacologic therapies for congenital and acquired heart disease, and (3) identify regenerative pathways or strategies for the failing heart.

Selected Publications

Azakie A, Fineman JR, He Y. Sp3 inhibits Sp1-mediated activation of the cardiac troponin T promoter and is downregulated during pathological cardiac hypertrophy in vivo. Am J Physiol Heart Circ Physiol 2006;291(2):H600-11.

Azakie A, Fineman JR, He Y. Myocardial transcription factors are modulated during pathologic cardiac hypertrophy in vivo. J Thorac Cardiovasc Surg 2006;132(6):1262-71.

Oishi P, Azakie A, Harmon C, Fitzgerald RK, Grobe A, Xu J, Hendricks-Munoz K, Black SM, Fineman JR. Nitric oxide-endothelin-1 interactions after surgically induced acute increases in pulmonary blood flow in intact lamps. Am J Physiol Heart Circ Physiol 2006; 290(5):H1922-32.

Azakie A, Larkin SB, Farrance IK, Grenningloh G, Ordahl CP. DTEF-1, a novel member of the transcription enhancer factor-1 (TEF-1) multigene family. J Biol Chem 1996; 271(14):8260-5.

Information last updated April 2007