University of Cincinnati Department of Pediatrics

Katherine Yutzey, PhD

Appointment

Professor

Phone

513-636-8340

Fax

513-636-5958

Bio

Visit Dr. Yutzey's Lab Web Site.

Katherine E. Yutzey, PhD, professor, joined the Division of Molecular Cardiovascular Biology at Cincinnati Children's Hospital Medical Center in 1995.

Dr. Yutzey is the first recipient of the Fifth Third Bank/Charlotte R. Schmidlapp Women Scholars Award and was also a recipient of a Children's Hospital Medical Center Trustee Award. Her work is also supported by grants from National Institutes of Health (NIH) and the American Heart Association

The focus of Dr. Yutzey's research program is the regulation of normal and abnormal heart development. Congenital heart defects represent one of the most common classes of human birth defects. Increasing evidence exists for a genetic basis of certain instances of congenital heart disease

The identification of genes responsible for these defects is an active area of research. Of equal importance are developmental studies identifying and characterizing how congenital heart defects arise during embryogenesis. These studies are dependent on the creation of well-characterized animal model systems that recapitulate human cardiovascular disease. One of the aims of the research program is to create transgenic mouse models of human congenital heart defects

The goal is to define the progression of these defects and to identify the origins of common cardiac malformations in developing embryos. The strategy is to manipulate critical regulators of heart development in specific regions of the heart at specific times during development in transgenic mice. Towards this end, several different DNA sequences that activate gene expression in different regions of the heart during development have been generated within the Division of Molecular Cardiovascular Biology

Recently, regulatory sequences that target alterations in gene expression to the precardiac region of the embryo before the heart has formed were identified. Additional DNA sequences are available that drive gene expression in the entire primitive heart or specifically in the atria or ventricles during development. With these reagents, it is now possible link temporally and spatially regulated genetic alterations in the developing heart with specific types of congenital heart disease

Recent efforts have been directed towards identifying regulators of early heart chamber development. Defects in heart chamber development represent the largest classes of human congenital cardiac anomalies. One of the few genes currently known to be associated with these defects is the transcription factor TBX5. Mutations in TBX5 have been identified in families with Holt-Oram Syndrome which includes atrial septal defects and other cardiac anomalies. Based on its expression pattern during heart development, Tbx5 is a strong candidate for one of the important regulators of heart chamber formation

An area of focus in the lab is the examination of Tbx5 function during normal heart development in chicken and mouse embryos. In addition, transgenic mice are being generated with altered Tbx5 expression and function in the developing heart

Holt-Oram Syndrome is associated with specific TBX5 mutations that likely produce proteins with altered regulatory functions. Studies are in progress in which mutant Tbx5 proteins are being expressed in the hearts of transgenic mice. The anticipated result that these mice will be born with congenital heart defects. These mice will then be used for examining the origins and progression of congenital heart lesions observed in the human population

Additional efforts in the lab are focused on the regulation of the earliest stages of normal heart development. Specifically, the molecular signals that specify some cells but not others as heart cells during embryonic development are being examined. These studies have potential applications to the treatment of degenerative cardiac disease. At present there is no reliable method for regenerating diseased cardiac cells or for driving multipotential cells such as embryonic stem cells into the cardiac lineage

The identification of specific molecular pathways involved in early cardiac development will provide potential targets for drug discovery and gene therapy. Mouse and chicken embryo culture systems are used in to examine the regulatory pathways that control early heart development. Through these studies, specific tissue interactions and molecular signals required for cardiac development have been identified. Combinations of signals that increase the numbers of cardiac cells will then be tested on multipotential stem cell populations. In the long term, these studies may be extremely valuable in efforts to generate increased numbers of cardiac cells for tissue engineering or a variety of therapeutic applications.

Credentials

BA Oberlin College, Oberlin, Ohio, 1986
PhD: Purdue University, West Lafayette, Ind., 1992
Fellowship: Cornell University Medical College, New York, Ny., 1992-1995

Position History

1992 - 1995 Post-doctoral Research Associate, Cornell University Medical College, New York, NY. Mentor: David Bader

1995 - 2002 Assistant Professor, Pediatrics-Affiliated, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center

2002 - 2007 Associate Professor, Pediatrics-Affiliated, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center

2007 - Present Professor, Pediatrics-Affiliated, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center

2004 - Present Director, Molecular and Developmental Biology Graduate Program, Cincinnati Children's Hospital Medical Center

Awards and Honors

1996-98 Trustee Grant Award, Children's Hospital Research Foundation
1998-99 Fifth Third Bank/Charlotte R. Schmidlapp Award
2001-2004 Established Investigator, American Heart Association
2002-2003 Co-Chair, Basic Cell and Molecular Biology-2 Peer Review Committee: American Heart Association-National
2002 Ad Hoc Peer Review: Cardiovascular B Special Emphasis Panel NIH
2002 Member Tissue Engineering Special Emphasis Panel NIH/NHLBI
2002-pres. Developmental Dynamics Editorial Board
2003 Program Project Grant Special Emphasis Panels (2) NIH/NHLBI
2003 Ad Hoc Peer Review: Cell Development and Function 5 (CDF-5) NIH
2003-pres. AHA Basic Research Council, Ohio/Virginia/Florida Affiliate
2004 Chair, American Heart Association, Basic-2 Peer Review Committee
2004-2005 Ad Hoc Peer Review: Cardiovascular Diff'n and Development (CDD) NIH
2005 AHA-National Science Classification Task Force
2005-pres. Stem Cells, Editorial Board
2005-pres. Weinstein Conference on Cardiovascular Development, Organizing Committee
2006-2010 Member, Program Project Review Parent Committee NIH/NHLBI
2007-presentDevelopmental Biology, Editorial Board
2008-present Fellow of the Graduate School, University of Cincinnati

Research

The focus of our studies is the molecular regulation of embryonic heart development. Experimental embryological, genetic and molecular approaches are used for mechanistic analyses of early cardiac lineage determination and heart morphogenesis. We use both chick and mouse embryonic systems to identify critical regulatory interactions responsible for these events and to manipulate these interactions in vivo. In addition, several in vitro culture systems have been developed in which to examine the molecular regulatory events that control cardiac lineage determination and early heart chamber morphogenesis. Together these strategies are employed to establish the relationships between signaling pathways and transcription factors that control the specification of the cardiomyogenic lineage and heart chamber formation. These studies have potential clinical implications in efforts to convert multipotential stem cells to the cardiac lineage and in the diagnosis and treatment of congenital heart disease.

Recent efforts in the lab have been directed towards identifying regulators of early heart lineage determination. These studies are designed to identify the molecular signals that specify some cells but not others as heart cells during embryonic development. One of the first genes expressed in the embryonic heart is the homeobox transcription factor nkx-2.5. We have identified early cardiac regulatory sequences of the nkx-2.5 gene and are studying the molecular regulatory interactions required for gene activation in the developing heart. Through these studies, specific tissue interactions and molecular signals required for cardiac development have been identified. In the long term, these studies may be extremely valuable in efforts to generate increased numbers of cardiac cells for tissue engineering or a variety of therapeutic applications.

An additional focus of the lab is the study of heart chamber formation. Defects in heart chamber development represent the largest classes of human congenital cardiac anomalies. An example of a developmentally regulated gene associated with these defects is the transcription factor TBX5. Based on its expression pattern during heart development, Tbx5 is a strong candidate for one of the important regulators of heart chamber formation. We are examining Tbx5 function during heart development in chicken and mouse embryos. A long term goal of these studies is the generation of transgenic mice born with congenital heart defects. These mice will then provide a unique tool for the examination of the origins and progression of congenital heart lesions observed in the human population.

Research Grants and Contracts

Current Support

Yutzey, K: The calcineurin/NFAT pathway in heart development Signaling Processes Underlying Cardiovascular Function/Project 2
National Institutes of Health (PO1 HL69779); 06/06/02 - 04/30/07
Total Direct Costs: $916,810

Yutzey, K: Regulation of valvuloseptal development by DSCR1 SCCoR in Pediatric Heart Development and Disease/Project 3
National Institutes of Health (P50 HL074728); 01/01/04 - 12/31/08
Total Direct Costs $1,135,000

Yutzey, K: Tbx20 regulation of heart valve development
National Institutes of Health (R01 HL082716); 07/01/06-06/30/10
Total Direct Costs $1,000,000

Yutzey, K: The Akt/FoxO pathway in heart development
National Institutes of Health (1P01 HL069779-06); 2002-2012
Total Direct Costs $1,053,839

Yutzey, K: Regulation of valvuloseptal development by DSCR1
National Institutes of Health (1P50 HL074728); 2004-08
Total Direct Costs $1,135,000.

Trainee Support

Member of training faculty for NIH training grants in Teratology, Cardiology, Pulmonary and Cardiovascular Biology, and Physiology at Children's Medical Center and The University of Cincinnati College of Medicine

2007-2008 American Heart Association-Great Rivers Affiliate, Pre-doctoral Fellowship
#0715360B The functions of Tbx20 and Twist1 in endocardial cushion development.
Elaine (Howells) Shelton, Fellow. K. Yutzey, Sponsor. Total direct costs $21,000.

2007-2009 American Heart Association-Great Rivers Affiliate, Pre-doctoral Fellowship
#0715107B NFATc1 regulation of extracellular matrix remodeling and cell proliferation in heart valve development.
Michelle Combs, Fellow. K. Yutzey, Sponsor. Total direct costs $42,000.

2007-2009 American Heart Association-Great Rivers Affiliate, Post-doctoral Fellowship
#0725321B Regulation of myocardial growth by FOXO transcription factors.
Heather Evans-Anderson, Fellow. K. Yutzey, Sponsor. Total direct costs $86,000.

2008-10 American Heart Association-Great Rivers Affiliate, Post-doctoral Fellowship
#0825627D Twist1 and Tbx20 function in heart valve development.
Santanu Chakraborty, Fellow. K. Yutzey, Sponsor. Total direct costs $88,000.

Presentations

"Pattern formation in early heart development" Department of Biology, Indiana-Purdue University at Indianapolis, Oct. 17, 1997.

"Patterning during early heart development" Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati, College of Medicine, Oct. 23, 1997.

"Anterior-Posterior Patterning" Councils on Basic Science and Cardiovascular Disease in the Young, American Heart Association National Meeting, Orlando, FL Nov. 8, 1997.

"Pattern formation in early heart development" Department of Anatomy, University of Wisconsin-Madison, April 28, 1998.

"Myogenesis" Discussion Leader, Weinstein Cardiovascular Development Conference, Nashville, Tenn., May 28-30, 1998.

"Embryology" Saturday Science Academy, Howard Hughes Medical Institute, Precollege Science Education Initiative for Biomedical Research Institutions, University of Cincinnati College of Medicine, Aug. 9, 1998.

"Molecular Regulation of Heart Patterning and Morphogenesis" Molecular Medicine Seminar
Children"s Hospital Research Foundation, Sept.17, 1998.