BBS Faculty Member - Caroline Burns

Caroline Burns

Department of Medicine

Massachusetts General Hospital-East
149 13th Street, CVRC, 4th Floor, 4138E
Charlestown, MA 02129
Tel: 617-643-4552
Fax: 617-726-5806
Email: cburns6@partners.org
Visit my lab page here.



Ischemic heart disease (IHD) is the most prevalent cause of death in the US, resulting from the human heart's failure to repair damaged myocardium following injury. Instead, scar tissue is deposited that diminishes heart function and/or causes sudden cardiac death. Recent findings, however, have fueled speculation that partial or full myocardial regeneration following ischemic injury might be achievable with novel therapeutic interventions. First, multi-potent progenitor cells capable of forming all of the differentiated cardiac lineages have been discovered in the mammalian heart. Secondly, adult zebrafish were found to regenerate myocardium following surgical resection of the ventricle apex. These data suggest that the capacity to regenerate heart muscle is a primitive trait that has been attenuated over time and, therefore, it is possible that endogenous cardiac progenitor cells (CPCs) could be activated in mammals to stimulate new myocardial production instead of scarring. To that end, our long-term goal is to exploit the genetic and cardiac regenerative attributes of zebrafish to characterize CPC properties in vivo and to identify the critical molecular programs driving myocardial regeneration.

Our goal is to identify the normal mechanisms by which CPCs are specified, expanded, and differentiated during embryonic development to ultimately augment the activity of either endogenous or transplanted CPCs for clinical use. The zebrafish is an excellent model system to study fate determination and stem cell biology as there are distinct genetic and transplantation advantages. As the developmental genetics of organ formation are highly conserved between fish and mammals, the pathways affecting fate decisions in zebrafish can be directly compared to that of humans. We are identifying master CPC pools within the developing teleost and dissecting their initial induction using both genetic and chemical-based screening strategies. Moreover, we have built new genetic tools that allow us to prospectively isolate these progenitor populations based on fluorescent marker gene expression. These tools will allow us to compare CPCs found in the embryo to those found in the adult during regeneration. The discovery that a relatively dormant adult CPC population can be activated upon injury by specific developmental programs to migrate, proliferate, and differentiate into new myocardium in zebrafish would have profound implications for regenerative medicine.



Last Update: 8/21/2013



Publications

For a complete listing of publications click here.

 


 

Burns CE, DeBlasio T, Zhou Y, Zhang J, Zon L, Nimer SD. Isolation and characterization of runxa and runxb, zebrafish members of the runt family of transcriptional regulators. Exp. Hematol. 2002; 30: 1381-9.

Burns CE, Traver D, Mayhall E, Shepard JL, Zon LI. Hematopoietic stem cell fate is established by the Notch-Runx pathway. Genes Dev. 2005; 19: 2331-2342.

Peng CY, YajimaH, Burns CE, Zon LI, Sisodia SS, Pfaff SL, Sharma K. Notch and MAML regulate Scl dependent interneuron cell fate. Neuron 2007; 53: 813-827.

White RM, Sessa A, Burke C, Bowman T, LeBlanc J, Ceol C, Bourque C, Dovey M, Goessling W, Burns CE, Zon LI. Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell. 2008; 2: 183-9.



© 2013 by the President and Fellows of Harvard College