Welcome to the Kirby lab!
Hello everyone! I’m glad I have this opportunity to lock in the Howard Hughes experience. First of all, it feels GREAT to be back at Duke. You know that warm, fuzzy feeling you get when you arrive home? I got THAT feeling. Nevertheless, I love home back in icy Ann Arbor, Michigan. In fact, that’s where this summer research experience really started. 
Living in a college town is AWESOME. Not only do you get to hang out on a great campus and see academia/city life merge, but you also have endless opportunities. To complement the research I would be doing on a congenital heart defect in the Kirby lab, I shadowed some of the top doctors and surgeons in the field at the University of Michigan Congenital Heart Center. It was there that I got to see the phenotype.
I was so impressed by Dr. Jennifer Hirsch, a pediatric cardiac surgeon at the center. What amazed me most was that she’d have Eminem or Fergie playing in the background as she inserted a piece of gore-tex to repair an ASD or VSD (septal defects). Now that’s talent.
It was with Dr. Caren Goldberg when I got to see patients with….*drumroll* HYPOPLASTIC LEFT HEART SYNDROME, the defect I am studying in the Kirby lab, a cell and developmental biology lab with a focus on the early stages of heart development. 
So what exactly IS hypoplastic left heart syndrome? It is the most lethal congenital heart defect, resulting in severe underdevelopment in structures of the left side of the heart (in diagram), namely the left ventricle which pumps blood to the entire body via the aorta. With reduced action of the left ventricle, there is mixing of blood and more strain on the right side of the heart to complete the important activities of the left side. Without intervention, babies will die within hours or days. Even after early intervention, patients must undergo further surgeries to reduce the strain on the right side of the heart. For example, i saw a few patients who were about to undergo the Fontan procedure in which the SVC and IVC (vena cavas) are connected to the pulmonary artery so that blood can just directly go to the lungs without passing through the right ventricle. This heart condition can be detected even at the fetal stage by an echocardiogram (notice the tiny left ventricle compared to the normal-sized right ventricle) :
What makes our research on hypoplastic left heart unique is that we’re studying it in an epidemiological context. A long-term study showed that PCB spills in the Baltimore area led to increased rates of hypoplastic left heart. We are studying how the PCB toxin interacts with different cell cycle proteins to inhibit cell proliferation in the ventricle, leading to its underdevelopment. Some of these cell cycle proteins we’re targeting may sound familiar, especially to those of you who took Bio 118…our current list includes p53, Rb, E2F, cyclin D1, cyclin E, and cyclin B. Most importantly, the zebrafish is being used to model hypoplastic left heart and has proven to be very effective. 
control fish (blue-stained heart) 
PCB-exposed fish (notice the “stringy” heart and swelling of the pericardium, the sac around the heart). Working on this project has been a lot of fun so far…take a look!! Pictures courtesy of the wonderful Alaina Pleatman.
Looking up which antibodies would best recognize zebrafish cell cycle proteins…rnrn
Martha, Laura, me
with Dr. Kirby
with the chick eggs, some lab members do microsurgery to extract the embryos
rnrn
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I’m glad I finally found an area of research I’m really interested in. Don’t get me wrong, I do like finding out about new genes and obscure proteins but sometimes it’s refreshing to just look at the BIG picture, as well. What I love most is that my project encompasses many of my interests such as epidemiology, pediatric cardiology, environmental science, and cell biology. Next post, I will introduce Dr. Margaret Kirby, my PI and Professor of Pediatrics and Cell Biology. Until then, take care!
June 5th, 2007 at 1:14 pm
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June 11th, 2007 at 2:26 pm
Wow Trisha, your post was very much more informative than mine, you really know what you’re doing. How do you induce the stringy-heart in the fish? Do you just dump the toxin in their tanks?
June 11th, 2007 at 2:59 pm
hey Monica! To expose them to PCB, we just put embryos in little vials full of it…it’s actually not sad because they don’t have any senses until 5 days so it’s ethical.
July 25th, 2007 at 12:45 pm
Dear Students,
I don’t wish to spoil your fun, because humor and passion are what drive all scientific advances and I do so want you to find a cure for HLHS. My baby, Jack was diagnosed with un-treatable HLHS at Children’s M in Chicago. We had to terminate, or carry to term an watch him die. (Norwood, and other procedures would not have saved him.) I see that you’ve possibly found evidence of environmental factors contributing to HLHS. I’ve had no exposure to PCB that I’m aware of, but will offer any help that I can. I wish you and your team all the success in the world. You can do it!