Q&A with Fabian Jimenez-Contreras: Exploring the ACE2 gene connection to blood pressure

Thursday, June 23, 2016

Born in Costa Rica but now living in Georgia, Fabian Jimenez-Contreras, a Duke University junior, is a Program to Awaken Early Interest in Research (POWER) researcher this summer inside the labs of the Duke O’Brian Center for Kidney Research (DOCK). He is exploring his research interests in the lab of Susan Gurley, MD, PhD, associate professor of medicine (Nephrology).

From gathering preliminary data to understanding the connection of the angiotensin converting enzyme 2 (ACE2) gene and blood pressure regulation, Contreras’s research and lab time with Dr. Gurley has built his excitement to pursue new research projects throughout his undergraduate years at Duke. In one of his current research projects, Contreras is focusing on knocking out the ACE2 gene in cardiac tissue to see if it has an effect on heart function.

Q: How did you find/pick Dr. Gurley for research experience?
A: Over the summer, I was selected for the DOCK POWER program, which is a program that was created in order to allow students research opportunities in the area of cardiology and nephrology. I had already been in Dr. Gurley’s lab a year before I started working on my project there. Since the fall 2015, I’ve been working on my project so I was actually elected to continue over the summer.

Q: What’s your research project?
A: The whole lab, more or less, works on the renin-angiotensin system, which is a hormone system that has relevance to nephrology because it regulates blood pressure and renal output. My project specifically has been in the focus of an enzyme called ACE2, which is short for angiotensin converting enzyme 2, an enzyme with ability to degrade certain hormones important to cardiovascular disease.

Q: Can you explain the connection between the ACE2 gene and blood pressure regulation?
A: The whole renin-angiotensin system in certain states of trauma regulates blood pressure so certain drugs like ACE inhibitors have been put on the market to regulate blood pressure and heart function.There’s some evidence that ACE2 actually down-regulates blood pressure. So we’re hypothesizing that perhaps knocking out ACE2 would lead to an increase in blood pressure because it’s not converting that angiotensin II into less active forms.

Q: What's the relationship between cardiology and nephrology when it comes down to cardiovascular and kidney disease?
A: All the organ systems inside the body are linked. In my understanding, cardiology and nephrology are specifically linked through blood pressure regulation. The kidney has a lot to do with how we regulate blood pressure through that renin-angiotensin system and through how much sodium retention the kidney decides.

Q: What have you found in your research so far?
A: In my project specifically, I’m still doing a lot of background studies. I’m working to develop certain transgenic mice to confirm that I have knocked out ACE2 in cardiac tissue specifically. That’s very pertinent to my project. I’m using different techniques such as qPCR and this mouse called “MTMG mouse.” That is the “Tomato reporter mouse.” Basically, it will tell me if I was able to knock out ACE2 in the heart tissue specifically.

Q: What have been the challenges conducting research on this project(s)?
A: With every research, any long-time researcher can tell you that a lot of research is at least some trial and error because you might hypothesize something. You might run an experiment that takes a long amount of time and then your results come back negative, which is always frustrating. It’s a part of research. You can adjust your experiments or form new hypotheses that can lead you to outcomes that will let you publish a paper and contribute to the scientific knowledge out there. I think that’s the hardest part of research, sometimes just having the patience. It feels different than what the public thinks research is. They just think you’re in the lab and then you make a huge discovery. Research isn’t always like that but that doesn’t mean it isn’t as rewarding because it is when you discover one little thing. When you’re able to do that, I find that really, really rewarding.    

Q: What have you found interesting about your findings in your research?
A: Before I came into the lab, I didn’t have much knowledge about nephrology and the renin-angiotensin system in general. Learning a lot more about their physiology is really interesting to me. Learning about how certain enzymes, certain chemicals, and certain pathways regulate everyone’s internal measurements when it comes to blood pressure is something that I find really interesting.

Q: What kind of outcomes are you and Dr. Gurley hoping to see in your research this summer?
A: Most recently, I added another portion of nephrology to my project. We are looking at a paper that was recently published about fatty acid oxidation in proximal tubular leads to renal fibrosis. I’m really excited. I wouldn’t say it’s completely different, but in the scope of nephrology, it’s different from what I’ve been working with, which is ACE2. I’m really excited to pursue that new project, which seems really interesting and I want to know more about it, go more on in-depth.   

Q: Do you think you’ll continue in research after this year?
A: Yes, I will. My goal at the end of my undergraduate career is to have collected enough research to be able to put together some sort of thesis—an honors thesis—that I’ll be writing my senior year. Throughout undergrad, I’ve been engaged in research and I plan to continue doing research in something that I really enjoy.

Q: Tell me something that surprised you about this experience so far.
A: I think the most surprising thing about this experience so far is that I didn’t realize how much scientists and doctors can work together. Before I came to college, I didn’t know that much about either and I didn’t really think about how they can be connected or not related. My first year here, I thought they were very different spheres, like scientists are in the lab and doctors are in the clinic. In the Division of Nephrology, most of the PIs also have a clinical component, and I see how invaluable it is to bring that practical clinical experience into a lab. It really helps the understanding of what important questions can be asked so the research can be done a certain way.

Q: What are you looking forward to in the near future with this project(s)?
A: I really would like to continue to develop the project. Every time that there’s a new experiment done or a new batch of data comes in that I’m able to analyze, it’s hard to tell in the future what new experiments we’re going to do but I love knowing there’s always so much more to be done.