Tag Archives: kidney

2018 Summer of Science – High blood pressure and your kidneys: A look at how we can limit hypertensive kidney injury

Research Project

It is estimated by the American Heart Association that over 103 million American’s have hypertension, more commonly known as high blood pressure, which can have many adverse effects on the health of an individual. The kidneys are the filtering system of our bodies and work to remove waste and excess products every single day. When an individual has high blood pressure the vessels carrying blood within the kidney can become damaged and cause an inflammatory response that can lead to impaired kidney function and injury. My project looks at how we can block inflammation caused by high blood pressure and preserve kidney function. We do this by administering an antibody, a protein that can bind to specific targets to block their function, thereby reducing the inflammatory signals in rats that are hypertensive. Over a two-week period, we monitor blood pressure, food intake, water intake, body weight, and urinary output to provide an index of kidney function. At the end of the two-week period, we harvest the kidneys and utilize microscopy and video imaging to directly determine kidney blood vessel function.  Using this approach, we can determine if the antibody treatment is protecting the kidney from hypertensive injury.  This information allows us to understand how inflammatory signals influence organ function and develop new targets for medications for individuals with high blood pressure.

Realities of Research

My experience in my research lab this summer has been pretty different from my past research experiences. My research in the past has focused mainly on cell culture and use of a mouse model for my work. This summer I utilized a rat model and equipment I was not accustomed to working with, such as, machines that measure rat blood pressures. With my experience, there was a bit of learning curve and presenting my project progress weekly at lab meetings was very intimidating at the beginning.  Shifting my focus to physiological research this summer also posed some challenges. When utilizing an animal model in physiological research there are many variables you have to account for. Most of these variables are out of your control so variation between experiments was common. Overall, this experience has helped shape who I am as a scientist and taught me how to successfully overcome obstacles. My project has produced promising data that suggests that inhibiting inflammation in kidneys that have been exposed to high blood pressure helps to preserve kidney function.

Life of a Scientist

A good day in lab usually consists of me coming into lab around 8AM and leaving around 5PM, but most days I find myself coming in early or leaving much later. I usually will take some work home with me but I always make sure I designate at least an hour every night to myself where I relax, catch up with friends, or catch up on my favorite shows. Although I tend to always be stressed about school work or a deadline, it’s made easier by the fact that I enjoy my work and what I study. I think the most rewarding part of any research undertaking is when you finish a project or find some promising data that help contribute to new scientific discoveries. Having an amazing lab team working alongside me also helps. I received some excellent guidance from many of the mentors in lab and especially from my PI who taught me the importance of oral and written scientific skills. I think it’s great having a close-knit group of individuals in lab that are always willing to help you succeed and help you troubleshoot an experiment when it does not work.

 

Brian Freeman is a senior at the University of California, Merced majoring in Biology with an emphasis in Microbiology and Immunology. He is a 2018 Short-Term Research Education Program to Increase Diversity in Health-Related Research (STRIDE) Fellow working with Dr. Edward Inscho at the University of Alabama at Birmingham. His fellowship is funded by the APS and a grant from the National Heart, Lung and Blood Institution (Grant #1 R25 HL115473-01). Upon graduating, Brian plans to enter a Biomedical PhD program and pursue a career in academia.
My Summer of Scientific Research

Over the summer I have been working at Emory University with Dr. Tansey and other lab members looking for potential causes of Parkinson’s disease (PD). Parkinson’s disease is an illness that damages important parts of the brain and nervous system. This can cause a loss in efficient body movement. We believe that a specific protein, something that the body naturally makes, called LRRK2 may play a role in this disease because there is an increased amount found in PD patients compared to healthy controls. Therefore, we have studied this protein by trying to pin point its location in the body and learning how it causes other PD symptoms such as inflammation. This research will not only provide answers for PD, but can be used to learn more about other neurodegenerative diseases. The goal is to one day cure such debilitating illnesses for everyone who is unfortunate to develop them.

Realities of Research

One of the biggest things I have learned about working in a lab is that your plan of action can suddenly change, while the goal stays the same. However, there are many times where you must go back to the “drawing board” and erase or insert something new. To me, going back and finding out that you have to try something new is a good thing. You are improving on your research and hopefully it will bring you closer to significant results. I also had other learning opportunities such as improving on specific lab techniques. During my BCA assay (Bicinchoninic Acid assay), which is a protocol used to standardize amounts of proteins in a sample, I had to perfect my pipetting skills for the assay to work. I practiced for hours to get the exact amount of solution every time I withdrew from a tube before I actually ran the real assay. This summer, my project started off bumpy because of an experiment not going as planned. I was taking tissue sections of kidney to stain and investigate for the colocalization of LRRK2 with the primary regulator NFAT (Nuclear Factor of Activated T-cells) and pNFAT (NFAT promoter) status in the nucleus. We were looking at these specific cells because they are involved with the immune system which LRRK2 seems to help regulate. However, after my staining protocol, the kidney cells would essentially combust. After many days of trial and error, we decided that there was not enough knowledge of kidney staining in our lab, and instead of spending time and resources to figure it out we moved on and started looking at a new location. There were plenty of times where we had to re-evaluate our plan, and as I said before I only see them as learning opportunities. Sometimes research is not always going to be straight forward where you make a hypothesis, go through an experiment, and at the end collect an answer. It can take a lot of time and creative thinking to get where you need to go.

Damaged kidney cells.

Life of a Scientist

Being a part of a lab is great for many reasons. One reason is that I prefer the type of work style that it offers. Those aspects include being able to have flexibility within your schedule and not having to be constantly micromanaged. Yet, I am still offered enough guidance to steer me on the right track. I love that every day is another day pushing towards a goal that you most likely had a hand in setting. I am also surrounded by people who all want to see each other succeed. Although everyone in the lab may be working on their own personal agendas, people are constantly helping others with their projects whether it’s by lending their skills for a certain assay or giving an extra hand to make timely experiments go by faster. I would go on to say that the entire science community within your field begins to feel more familiar as your work progresses, as well. I value this idea of a connected community within my workspace. Overall, my experiences in my lab this summer were positive and resourceful. Of course, I have witnessed complications occurring in the lab such as assays not going as planned or having to re-due them because of minor mistakes. Human error constantly occurs and I have learned that you can only work with it and make sure to try as hard as possible to get accurate, significant results. Knowing that I could make a career into doing what I love, conducting science and answering important questions that benefit humanity, gives me the motivation of becoming a neurologist in the future.

Chayla Vazquez is a rising junior at Emory University in Atlanta, GA where she is majoring in Neuroscience and Behavioral Biology, with a minor in Ethics. She is working at Emory over the summer with Dr. Malu Tansey as an Undergraduate Summer Research Fellow (UGSRF) funded by the American Physiological Society. Chayla strives to become a biomedical scientist and utilize her skills in research to help people who struggle with cognitive defects.
The Life of a Summer Student Researcher

Childhood obesity has become a major health issue in the United States recently. Research studies show that childhood obesity is associated with an increased risk of declined renal function, which is defined as renal injury. Since renal hyperfiltration, which is when the kidneys are working more to than needed, this leads to excessive amounts of protein to be produced in the urine (proteinuria). This condition is typically associated with obesity. The current study will determine if we prevent the renal hyperfiltration, can we decrease proteinuria and/or renal injury?

Working on ground breaking research and being in an environment that is focused and effective was eye-opening for me. I enjoyed being around scientists that had similar mindsets and were able to help me develop a scientific mind of my own. It surprised me that everyone was so open and welcoming to a new unexperienced college student. But it made me more comfortable, especially when some of my experiment’s failed, but they were very helpful and encouraging throughout the entire process. During my time in the lab the initial study I worked on was not successful, so I was give the study I have now and the results that were collected were what my research host expected and it was a successful study that will be continued.

Being a scientists is like riding a roller coaster every day that you enter into the lab. Some days you are so busy with experiments that you forget to eat lunch. But then other days are very slow, because you are waiting on data or results. It is a great environment to learn not only about science but about yourself, how you manage time, how you interact with people, and how well you work alone. I think the best part about being a scientist is that every day is a new challenge because every day you are working on something that could possibly change the world. I think that worst part is that even if you do everything correctly the data can still not turn out how you want it. But overall I really enjoyed the team aspect of working in a lab. Everyone in the lab helps everyone on their projects and vice versa, because everyone wants to see the lab/experiments succeed because it could have a positive impact on the world.

Alyssa Pennington is a senior majoring in Chemistry at Jackson State University. Alyssa is working in Dr. Jan Michael Williams lab at the University of Mississippi Medical Center in Jackson, MS. Alyssa is a second year Short-Term Education Program for Underrepresented Persons (STRIDE) Fellow which is funded by the APS and a grant from the National Heart, Lung and Blood Institute (Grant # 1 R25 Hl115473-01). After graduation Alyssa plans to pursue a career in medicine and research.
Football-Like Kidneys and Galaxy-Like Cells

The effects of Polycystic Kidney Disease (PKD) are astounding. Kidneys, normally the length of a baseball, can grow to be the size of a football with fluid filled cysts covering the entire organ. Oftentimes, the disease can cause heart failure. This summer in Dr. Thomas Weimbs’ lab at the University of California, Santa Barbara, I researched one of the pathways that this disease affects. Specifically, a process called macroautophagy is necessary for kidneys to function properly. In macroautophagy, cells designate and target specific organelles or molecules to be broken down, send a structure to surround them, and then subsequently degrade the organelle or macromolecule (Johansen & Lamark, 2011). Yet in PKD, this process does not occur as it normally would in a healthy individual (Zhu, Sieben, Xu, Harris, & Lin, 2017). This dysfunctional pathway, among others resulting from the disease, results in kidneys that cannot function normally to remove waste from the blood and body. I am looking into what could regulate this decrease in autophagy. Is it the overexpression of a specific protein? And if so, what treatments mitigate this effect? Though this may seem to be a small part of the disease as a whole, it is important to understand the individual mechanisms and pathways within the disease to find new and effective therapies.

Realities of Research

Beginning this project was daunting. There is an incredible wealth of knowledge and research concerning Polycystic Kidney Disease that I had never been exposed to; I needed to look into these topics and understand background information so I could critically think about my project. Initially, reading scientific papers on this topic was very time consuming – I looked into every pathway, gene, and protein that I didn’t recognize in the literature. But slowly, this process became easier, and the topics became more familiar. Now, 10 weeks later, I am more confident in my ability to read and understand the scientific literature that is closely related to this topic.

I am also more comfortable with the hands-on lab techniques that I explored and focused on during my research internship. Specifically, I dedicated many weeks to microscopy, a technique that I had not ever been extensively exposed to. I find it incredible to look at the cells that I cultured and treated with different drugs, plasmids or antibodies up close. And though I didn’t expect it, I actually find the photos that result from my immunofluorescence experiments quite beautiful – I think they look like multi-colored galaxies.

These past 10 weeks have been both enlightening and frustrating at the same time – but mostly they have been rewarding. Though it was disappointing to have experiments that I spent over a week preparing yield no results, it was even more exciting when I did see results for the first time. I’ve learned the value of patience in the lab and careful, meticulous work. I’ve learned how important it is to put in outside work to reap the benefits of the environment you are in. And lastly, I’ve learned to not give up if something does not work. Instead, I analyze why it happened, and try again.

This summer has exposed me to a new and exciting realm of biology. I am incredibly grateful for the opportunity to have been connected with new peers and mentors, and to make a little dent in a very big and profound research topic.

References

  1. Johansen, T., & Lamark, T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 7(3), 279–296, 2011.
  2. Zhu, P., Sieben, C. J., Xu, X., Harris, P. C., & Lin, X. Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model. Human Molecular Genetics 26(1), 158–172, 2017.
Madeline Matthys is a senior at Duke University in Durham, NC . She is majoring in Biology and minoring in Chemistry. With the generous help of the American Physiological Society through the Undergraduate Summer Research Fellowship program, Madeline worked in Dr. Thomas Weimbs’ lab at the University of California, Santa Barbara in Santa Barbara, CA. Madeline plans to continue biological research and after she receives her Bachelors of Science, she hopes to attend medical school.