Studying zebrafish to understand cardiac disease

This article is part of our Summer Sojourns 2013 series highlighting summer adventures of FIU students. Chavely Valdes Sanchez, a senior majoring in biology, was one of 44 undergraduate students around the country accepted into the 2013 Harvard Stem Cell Institute Internship Program, which provides participants with a challenging summer research experience in a cutting-edge stem cell science laboratory.

This year, I was selected to be a 2013 Howard Hughes Medical Institute EXROP recipient – which meant that I would have the chance to conduct research with highly recognized scientists in their respective fields. Since at FIU I am part of Irina Agoulnik’s cancer research lab (in the Department of Cellular Biology and Pharmacology at the Herbert Wertheim College of Medicine), I wanted to spend my summer conducting research in a different field. Thus, I chose stem cell research specific to cardiac development at the Harvard Stem Cell Institute which is affiliated with Harvard Medical School.

I spent my summer in Caroline and Geoffrey Burns’s lab (in the Massachusetts General Hospital) studying cardiovascular diseases and cardiac development. We used the zebrafish as our study model which made this experience much more fascinating. The zebrafish is a fantastic organism to use for cardiac development because it is transparent during early developmental stages and can also live without a heart for up to three days. This means that we can literally see through the fish and watch its heart pump blood to the entire body. Also, we can induce cardiac defects to the zebrafish embryo and still be able to obtain results since the embryo can live with no circulating blood for three days.

My research project focused on the outflow tract (OFT) of the zebrafish heart. The OFT is composed of elastin and smooth muscle and it is an extension of the ventricle in the zebrafish heart. Since the OFT is essential for pumping blood to the body and lungs any defect to this region will reduce blood circulation. Furthermore, there is a condition in humans known as Supravalvular Aortic Stenosis (SVAS) which results from a point mutation in the elastin gene. This mutation decreases elastin levels in the OFT region of the human heart. Along with a decrease in elastin levels there is an increase in smooth muscle proliferation which simply means that the OFT becomes more narrow and blood flow is reduced. This interaction between elastin and smooth muscle in not completely understood and so I tried to address this issue through my research.

Once the program ended, Valdes-Sanchez presented her work at a symposium.

My project targeted the nitric oxide- guanylyl cyclase pathway since it is involved with smooth muscle and elastin regulation. My experiments consisted of treating zebrafish embryos with chemicals that inhibit key players in this pathway. Through inhibition of certain molecules we were able to mimic aspects of SVAS in humans. Finally, we proved that inhibition to the nitric oxide- guanylyl cyclase pathway reduces OFT differentiation during cardiac development. This indicates that in order to understand SVAS we need to set a greater focus on this pathway.

Through my research experience I gained an insight into a different field of science which added to my growth as a scientist.  I was given the opportunity to work in a Harvard lab which means that resources are abundant and creativity is the main focus. My training was based mostly on critical thinking which greatly enhanced my education. Opportunities that universities such as Harvard offer are unimaginable and with this in mind I learned that as students we should not limit ourselves. We should not be afraid to engage in new challenges and always strive to leave our comfort zone. Spending my summer at Harvard was more than I could have asked for and I am truly grateful for this opportunity.

– Chavely Valdes Sanchez