Thomas Bartman, MD, PhD
Appointment
Assistant Professor of Pediatrics, University of Cincinnati College of Medicine
Email
thomas.bartman@cchmc.org
Phone
513-636-9902
Fax
513-636-7868
Bio
Approximately 1% of newborns have structural malformations of the heart, making congenital heart disease (CHD) a leading cause of neonatal morbidity and mortality. While some infants with CHD have defined genetic syndromes, such as DiGeorge syndrome or Holt-Oram syndrome, the majority of cases are non-syndromic. Because the risk of CHD in siblings of patients with CHD is increased 2-3 fold above the population risk, there is clearly a genetic component to the development of CHD even in the absence of a clearly defined syndrome. However, very little is known about the genetics of CHD and we have identified very few genes as being predisposing to or causative of CHD.
Our lab uses the zebrafish to attempt to identify genes which are critical for the proper morphogenesis of the heart. The zebrafish is ideal for such studies because the embryos are externally fertilized and transparent, which allows for the direct visualization of the heart during organogenesis, and because of the ability to do forward-genetic studies in the zebrafish. The later feature allows for random introduction of mutations into the genome to assay for developmental perturbations that result from the introduced mutations. In this way, all of the genes involved in a developmental process can be identified in an un-biased fashion.
Our previous work has focused on the zebrafish line cardiofunk, in which endocardial cushions do not form. cfk encodes a novel actin expressed in the heart during organogenesis, and the cfk-s11 allele contains a dominant negative mutation which interferes with myocardial function. This led to the discovery that myocardial function is required for the development of endocardial cushions, as verified in studies with silent heart embryos and embryos treated with inhibitors of myofibrillar ATPase. What has not been answered is the exact mechanism by which contractility affects cushion development. One possibility is that alterations in blood flow affect shear stresses on the endocardial cells, which is well known to be important in affecting the gene expression profiles of endothelial cells. Another possibility is that altered myocardial function affects the expression or secretion of molecules that are required to signal to the endocardium to initiate cushion development. The main focus of the lab is to address this very issue through the study of cardiofunk, as well as other mutants with poor early heart function.
The other main focus of the lab is to study the role of proteoglycans in early heart function and form. We are working with the jekyll mutant, as well as s434 (an unidentified gene which interacts with jekyll), to determine the cellular and functional defects that arise when proteoglycans are absent from the developing heart. Our focus is on understanding specifically the roles of chondroitin-dermatan sulfate proteoglycans, since these molecules have been studied relatively little for their role in early development.
Credentials
Baccalaureate: Massachusetts Institute of Technology, Life Sciences, 1989
MD/PhD: Molecular Biology and Genetics, Temple University, Philadelphia, PA, 1996.
Residency: Pediatrics, University of California, San Francisco, 1996-1999.
Fellowship: Neonatology, University of California, San Francisco, 1999-2003.
Postdoctoral Research: Cardiovascular Research Institute (Didier Stainier), UCSF, 2000-2003.
Certification: Pediatrics, 1999. Neonatology, 2003.
Position History
Assistant Professor, Divisions of Developmental Biology, Pulmonary Biology and Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2003 - present
Awards and Honors
- Melvin Grumbach Award for Postdoctoral Research, UCSF Department of Pediatrics, 2003
- Weinstein Cardiovascular Development Conference, Outstanding Presentation, 2002
- Mary DeLeo Award for Outstanding Research in Oncology, Temple University, 1996
Research
Cardiovascular development in zebrafish, especially endocardial cushion and heart valve development.
Congenital heart disease in newborns; genetic factors influencing heart malformations in the fetus and newborn.
Visit the Bartman Lab web site.
Research Grants and Contracts
Howard Hughes Medical Institute 9/2000-7/2003, Postdoctoral Research Fellowship for Physicians.
NIH K12HD28827 9/2003-8/2005
American Heart Association Scientist Development Grant 1/2006-12/2009, Analysis of NFATc1 as the Mechanism by which Early Heart Function Regulates Endocardial Cushion and Valve Morphogenesis
March of Dimes 6/2006-5/2009, Role of Chondroitin and Dermatan Sulfatation in Endocardial Cushion Morphogenesis
Publications, Most Recent
Thomas Bartman's publications as listed by PubMed
Maeda Y, Suzuki T, Pan X, Chen G, Pan S, Bartman T, Whitsett JA. (2008) CUL2 is required for the activity of hypoxia-inducible factor and vasculogenesis. J Biol Chem. 283:6084-92.
Beis D, Bartman T, Jin SW, Scott IC, D'Amico LA, Ober EA, Verkade H, Frantsve J, Field HA, Wehman A, Baier H, Tallafuss A, Bally-Cuif L, Chen JN, Stainier DY, Jungblut B. (2005)
Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development. Development 132:4193-204.
Stainier DYR, Beis D, Jungblut B, Bartman T. (2002) Endocardial Cushion Formation in Zebrafish. In: Stillman, Bruce (ed), 67th Cold Spring Harbor Symposium on Quantitative Biology. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Professional Organization Memberships
- Society for Pediatric Research
Invited Research Presentations
Bartman, T.; Walsh, E.; Wen, K.; McKane, M.; Ren, J.; Alexander, J.; Rubenstein, P.A.; Stainier, D.Y.R.: Altered Cardiac Contractility Disrupts Proper Cushion Morphogenesis. Weinstein Cardiovascular Development Conference, May 15-17, 2003; Boston, MA.
Bartman, T.; Walsh, E.; Stainier, D.Y.R.: A Mutation in a Novel Actin Disrupts Endocardial Cushion Formation in Zebrafish. Weinstein Cardiovascular Development Conference, May 16-18, 2002; Salt Lake City, UT.
Related Areas
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