Monthly Archives: March 2019

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.
Seal Tissues, Antioxidants, and -80 Degree Freezers

Research Project

The Weddell Seal is able to hold its breath for 30 minutes at a time while diving in frigid Antarctic waters. To avoid running out of oxygen during this long dive, the seal collapses its lungs and restricts blood to only essential organs. In other mammals, the process of cutting off blood flow and the supply of oxygen to a tissue, only to reoxygenate those tissues at a later point (when the seal resurfaces) generates reactive oxygen species. The process causes oxidative stress, which damages the tissue. This summer I am studying some of the physiological adaptations that enable Weddell seals to avoid the detrimental effects of oxidative stress at a cellular level. At the moment I am focusing on catalase, an antioxidant enzyme that is good at breaking down hydrogen peroxide (a reactive oxygen species), to see if its activity is higher in seal tissues than in other mammals. The long-term goal of this research is to apply our understanding of how seals cope with oxidative stress to human organ transplants.

Realities of Research

This is my first time working in a lab so most everything has been entirely new to me, from the constant buzz of the -80 degree freezers to the techniques of growing cells to the precise technology. Besides learning many science skills, I’ve spent the last several weeks seeing how rare (and exciting!) it is for an experiment to work and yield significant results. Fingers crossed for the rest of my project!

Life of a Scientist

Besides working on my own research, I’ve been involved in numerous projects throughout the lab, so I’ve seen how research questions evolve and overlap and shift as researchers collaborate with one another. The aspect of collaboration within my lab has been one of the coolest things to witness this summer, especially since each researcher is doing distinct work. I’ve also loved getting to know my coworkers, and we’ve had cool conversations about new scientific discoveries and endless career options.

Throughout the summer, I’ve really appreciated being able to hold on to a big picture – of the real, live seals – even as I work at the microscopic, cellular level. I think this seal research is pretty darn cool.

 

Eliza Skoler is a senior Biology major and Neuroscience minor at Carleton College in Northfield, MN. She is a 2018 UGSRF fellow working in Dr. Allyson Hindle’s lab at Massachusetts General Hospital in Boston. She plans to pursue a career in public health.
Investigating the role of the androgen receptor in polycystic ovarian syndrome

Research Project

For the past summer, I have been working in laboratory of Dr. Sheng UW at the Johns Hopkins School of Medicine. In the Wu lab, we are investigating the etiology of polycystic ovarian syndrome or disease (PCOS/PCOD). One of the major clinical presentations of PCOS is high levels of androgens, a condition known as hyperandrogenism, and the Wu lab focuses on the androgen receptor (AR) which binds to androgen outside of cells and acts inside the cell to express certain genes. The mouse model that we use mimics hyperandrogenism by exposure to dihydrotestosterone (DHT), which is present in low amounts in women without PCOS. To investigate mechanisms of hyperandrogenism and the AR, knockout mice without the receptor are compared to control mice, enabling us to investigate the effects of differential levels of DHT and the role of the AR on fertility, gene expression, protein and RNA levels, adipose tissue, and ovarian morphology (Wu et al., 2014). Despite the prevalence of PCOS in women of reproductive age, and its association with metabolic dysfunction, infertility and hirsutism, the exact cause is not known and effective treatment options are not available. By elucidating the pathophysiology of PCOS, treatment can be designed to target the cause as opposed to only clinically managing the symptoms temporarily.

Realities of Research

Although the prospect of doing research in a lab might sound like it involves the use of expensive equipment and the newest technology (and in many cases this is very true), a large portion of research involves spending hours maintaining and genotyping new litters, waiting for assays and reactions to finish, and pipetting hundreds of samples. Experiments sometimes work, and at other times they fail and must be repeated. Small errors in pipetting or mindlessly forgetting to include a certain solution can cause time-consuming experiments to fail. But, the most critical learning experiences I have had thus far were assessing what went wrong and fixing it by. Results are also not immediate; it takes several weeks before the effects of DHT can be assessed. Confirming the genotypes of our mice is critical to make sure that we are investigating what we claim to be, and ensuring DHT surgeries are done at the correct time requires attention and organization. Preliminarily, the effects of DHT we have observed have been physiologically plausible, although much of the data collection of the study is still ongoing.

Life of a Scientist

Simultaneously, the best and worst parts about doing research in a lab are that the hours are flexible and I can plan my week. But, this also means spending evenings working due to long wait times for experiments that extend past the usual 9 to 5 working day, or because a protocol calls for a certain experiment to be done at a certain time. The independence is exciting, but can also be intimidating as I must be aware of what needs to be done and when. However, research is collaborative. As the youngest and most inexperienced person in my lab, I am always learning how to do new experiments and how to interpret and analyze data. Others are always offering me tips and tricks, supporting me when I fail, and helping me deal with my constant fear of getting bitten by mice. The most rewarding moments of the summer so far have been presenting data to my PI and co-PI, and teaching members of the lab how to complete a computerized tissue analysis that had not been done in our lab before. The most disappointing? Waking up early to complete a western blot protein analysis only for it to fail – not once, but multiple times!

References:

  1. Wu, S., Chen, Y., Fajobi, T., DiVall, S., Chang, C., Yeh, S. and Wolfe, A. (2014). Conditional Knockout of the Androgen Receptor in Gonadotropes Reveals Crucial Roles for Androgen in Gonadotropin Synthesis and Surge in Female Mice. Molecular Endocrinology, 28(10), pp.1670-1681.
Gopika Punchhi is a rising senior at Johns Hopkins University in Baltimore, MD, pursuing degrees in Molecular and Cellular Biology and Public Health Studies. Through the Undergraduate Summer Research Fellowship (UGSRF) program, she is spending the summer working under Sheng Wu, PhD, an associate professor in the department of Physiology at the Johns Hopkins School of Medicine. UGSRF is funded by the APS. Gopika plans on attending medical school to become and gynecologist or endocrinologist, while also continuing involvement in molecular and population-level research in these fields.