Lab
Scott Laboratory
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Statement of Research Interest
RESEARCH INTERESTS:
- specification and development of cardiovascular progenitor cells
- conserved cis-regulatory elements involved in cardiac development and disease
- early heart development
- Apelin receptor signaling
RESEARCH ACTIVITIES:
Congenital heart disease affects close to 1% of live births, and can have a severe impact on the health and mortality of children. Despite many years of research, little is known about the stem cells that go on to form the different types of cells found in the heart. These cells are called cardiac progenitors. As they are the “building blocks” of the heart, cardiac progenitors are an ideal vehicle to fix the damaged heart. We study this in zebrafish embryos, which allow live and direct visualization of all stages of heart development. Further, the adult zebrafish heart can fully regenerate, a process we seek to understand via the lens of cardiac progenitor biology in order to allow human cardiac repair. Using the advantages of the zebrafish embryo, we employ genetic, genomic, embryological, live imaging and biochemical approaches to study in real time the earliest events of cardiovascular development.
Current research in the lab is focused on understanding the earliest events of cardiac development, and how dysfunction in the gene regulatory networks that govern heart development causes congenital heart disease. In close collaboration with the lab of Dr. Michael Wilson, we use a comparative genomics approach to identify cis-regulatory elements conserved from zebrafish to human and active during heart development. We have identified conserved enhancers responsive to the activity of key cardiogenic factors such as Gata5 and Aplnr. A number of these first become accessible during gastrulation, as cardiac fate is first established, suggesting that these elements may build the initial "foundation" upon which later cardiac development operates. We continue characterization of a large number of these elements to define an "enhancer grammar" that controls cardiac-specific gene expression patterns. Further, in collaboration with the Cardiac Genome Clinic at SickKids we have identified ultrarare variants in these elements that occur in congenital heart disease patients, and continue to characterize the contribution of these variants to congenital heart disease.
It is hoped that by combining genetic, genomic, embryological and imaging approaches we will gain a deeper understanding of the developmental processes that regulate heart development. In the future, we hope to apply this knowledge to therapeutic approaches for congenital and adult-onset cardiovascular disease.
- specification and development of cardiovascular progenitor cells
- conserved cis-regulatory elements involved in cardiac development and disease
- early heart development
- Apelin receptor signaling
RESEARCH ACTIVITIES:
Congenital heart disease affects close to 1% of live births, and can have a severe impact on the health and mortality of children. Despite many years of research, little is known about the stem cells that go on to form the different types of cells found in the heart. These cells are called cardiac progenitors. As they are the “building blocks” of the heart, cardiac progenitors are an ideal vehicle to fix the damaged heart. We study this in zebrafish embryos, which allow live and direct visualization of all stages of heart development. Further, the adult zebrafish heart can fully regenerate, a process we seek to understand via the lens of cardiac progenitor biology in order to allow human cardiac repair. Using the advantages of the zebrafish embryo, we employ genetic, genomic, embryological, live imaging and biochemical approaches to study in real time the earliest events of cardiovascular development.
Current research in the lab is focused on understanding the earliest events of cardiac development, and how dysfunction in the gene regulatory networks that govern heart development causes congenital heart disease. In close collaboration with the lab of Dr. Michael Wilson, we use a comparative genomics approach to identify cis-regulatory elements conserved from zebrafish to human and active during heart development. We have identified conserved enhancers responsive to the activity of key cardiogenic factors such as Gata5 and Aplnr. A number of these first become accessible during gastrulation, as cardiac fate is first established, suggesting that these elements may build the initial "foundation" upon which later cardiac development operates. We continue characterization of a large number of these elements to define an "enhancer grammar" that controls cardiac-specific gene expression patterns. Further, in collaboration with the Cardiac Genome Clinic at SickKids we have identified ultrarare variants in these elements that occur in congenital heart disease patients, and continue to characterize the contribution of these variants to congenital heart disease.
It is hoped that by combining genetic, genomic, embryological and imaging approaches we will gain a deeper understanding of the developmental processes that regulate heart development. In the future, we hope to apply this knowledge to therapeutic approaches for congenital and adult-onset cardiovascular disease.
Lab Members
| Carlisle, Casey Graduate Student | Erkut, Esra Graduate Student | Fahim, Maria Graduate Student |
| Liu, Cherry Graduate Student | McLeod, Gwynneth Graduate Student | Rosenthal, Shimon Graduate Student |
| Saba Echezarreta, Victoria Graduate Student | Stutt, Nathan Graduate Student | McDonald, Laura Research Staff |