Yi-Tang Tseng Associate Professor of Pediatrics (Research)

My graduate training was in pharmacology and toxicology (University of Mississippi Medical Center, 1994). After finishing a cardiovascular research fellowship in Harbor-UCLA Medical Center I moved to Women & Infant's Hospital, Brown Medical School.
My main research interest has been on signaling pathways regulating cardiomyocyte growth and proliferation. Currently we are focusing on the effects of beta-adrenergic receptor and PI3K signaling pathway on the regulation of cardiomyocyte proliferation during the transition from fetal to neonatal stages. Multiple in vitro and in vivo approaches are used in our study. A new animal model was established in our laboratory in which overexpression of cardiac-specific PI3K can be induced or repressed with a tetracycline transactivator-controlled binary system. This conditional transgenic animal model is been applied to investigate 1) the critical role of PI3K signaling in regulation of cardiomyocyte proliferation; and 2) the effect of PI3K signaling in acute cardiac injury.

Brown Affiliations

Research Areas

scholarly work

Tseng Y-T, Yano N, Rojan A, Stabila JP, McGonnigal BG, Ianus V, Wadhawan R, Padbury JF. Ontogeny of Phosphoinositide 3-Kinase (PI3K) Signaling in Developing Heart: Effect of Acute beta-Adrenergic Stimulation. Am J Physiol Heart Circ Physiol 289: H1834-H1842, 2005.

Hleb M, Murphy S, Wagner EF, Hanna NN, Sharma N, Park J, Li XC, Strom TB, Padbury JF, Tseng YT, Sharma S. Evidence for cyclin D3 as a novel target of rapamycin in human T lymphocytes. J Biol Chem 279: 31948-31955, 2004.

Wadhawan R, Tseng YT, Stabila J, McGonnigal B, Sarkar S, Padbury J. Regulation of cardiac beta1-adrenergic receptor transcription during developmental transition. Am J Physiol Heart Circ Physiol 284: H2146-H2152, 2003.

Tseng YT, Kopel R, Stabila JP, McGonnigal BG, Nguyen TT, Gruppuso PA, Padbury JF. beta-Adrenergic receptors (betaAR) regulate cardiomyocyte proliferation during early postnatal life. FASEB J 15: 1921-1926, 2001.

Tseng YT, Stabila JP, Nguyen TT, McGonnigal BG, Waschek JA, Padbury JF. A novel glucocorticoid regulatory unit mediates the hormone responsiveness of the beta1-adrenergic receptor gene. Mol Cell Endocrinol 181: 165-178, 2001.

Tseng YT, Stabila J, McGonnigal B, Nguyen TT, Padbury JF. An inversed cAMP response element mediates the cAMP induction of the ovine beta1- adrenergic receptor gene. Biochem Mol Biol Int 46: 1127-1134, 1998.

Padbury JF, Tseng YT, McGonnigal B, Penado K, Stephan M, Rudnick G. Placental biogenic amine transporters: cloning and expression. Mol Brain Res 45: 163-168, 1997.

Tseng YT, Tucker MA, Kashiwai KT, Waschek JA, Padbury JF. Regulation of beta1-adrnoceptors by glucocorticoids and thyroid hormones in fetal sheeps. Eur J Pharmacol (Mol Pharmacol Sec) 289: 353-359, 1995.

Tseng YT, Wellman SE, Ho IK. In situ hybridization evidence of differential modulation by pentobarbital of GABAA receptor alpha1- and beta3-subunit mRNAs. J Neurochem 63: 301-309, 1994.

Tseng YT, Miyaoka T, Ho IK. Region specific changes of GABAA receptors by tolerance to and dependence upon pentobarbital. Eur J Pharmacol 236: 23 30, 1993.

research overview

Our studies are focused on the signal transduction pathways important for regulation of cardiac myocyte proliferation during the transition from fetal to early postnatal life.

research statement

Our studies are focused on the signal transduction pathways important for regulation of cardiac myocyte proliferation during the transition from fetal to early postnatal life. The growth of cardiac myocytes switches from hyperplasia to hypertrophy shortly after birth. The molecular mechanisms responsible for the switch are not well understood. We have demonstrated that beta-adrenergic receptors (betaAR) are involved in regulation of neonatal cardiac myocyte proliferation, and that this mitogenic control is in large part mediated via the phosphoinositide 3-kinase (PI3K)/p70 S6 kinase (p70S6K) pathway. We examined the expression and activity of PI3K signaling during development and shown that there is a globally high input of cardiac PI3K signaling activity during late gestation and in the early postnatal days of development, but not in postnatal and adult life. The high signaling activity occurs when cardiac myocytes are undergoing hyperplastic growth. In neonatal rats, when cardiac p70S6K activity is already maximal, there is no further activation by betaAR stimulation. In contrast, acute betaAR stimulation results in activation of p70S6K at later stages when the endogenous activity is low. Our findings suggest that betaAR activation, via the PI3K signaling pathway, plays a significant role in regulation of cardiac myocyte proliferation in a development-dependent manner. We hypothesize the PI3K signaling pathway is critical for regulation of cardiac myocyte proliferation during the transition from fetal to early postnatal life. Attenuation of the PI3K signaling pathway underlies terminal differentiation in postproliferative cardiac myocytes. We further hypothesize that activation of the PI3K signaling pathway in postproliferative cardiac myocytes will augment cardiac myocyte proliferation in response to ischemic injury.

We have engineered a tetracycline transactivator-controlled conditional transgenic mouse line with cardiac-specific overexpression of PI3K. This new transgenic animal model allows us to induce or suppress cardiac PI3K at desirable time points during development and address the question whether temporal overexpression of PI3K signaling in the heart can stimulate cardiac myocyte proliferation in postproliferative stages without causing cardiac hypertrophy that is normally seen in constitutive overexpression animal models. Our recent data suggests that cardiac-specific conditional overexpression of PI3K in the postnatal animal improves myocardial function. There is emerging evidence for cardiac myocyte proliferation in the regions adjacent to myocardial infarction in human and in animal models. We are using the new animal model to address the role of PI3K signaling in cardiac remodeling following myocardial infarction. These studies will contribute to our understanding of the regulation of cardiac proliferation during the perinatal transition and in pathological conditions during adult life.

funded research

NICHD Program Project PO1, 1996 –2001
"The Biological Basis for Perinatal Transition
Project III, Developmental Regulation of the beta1-Adrenergic Receptor Gene"
Role: Co-investigator & Director of Molecular Biology Core
Direct cost: $660,720

Charles Hood Foundation, Child Health Research Grant
"Mechanisms of Glucocorticoid-Induced Hypertrophy in the Developing Heart"
Role: Principle Investigator
Total cost: $100,000

NIH COBRE for Perinatal Biology
1 P20 RR018728-01, 10/01/2003-09/30/2008
Program Director: James F. Padbury
"Project II, Signaling Pathways Regulating Cardiomyocyte Proliferation"
Role: Principal Investigator of Project II
Direct cost: $581,213