Supervisor: Gavin Oudit
Project: The role of an enzyme in understanding sex differences in diabetic cardiovascular disease
Bachelor of Science with Honors in Physiology
Why did you choose the degree program you are in?
I chose physiology because of its focus on research applications and its appreciation for the body as an intricate and interconnected system. The physiology program has given me the tools, support, background knowledge to contribute to various research projects at the university.
What did you get to work on throughout your studentship?
I've had the opportunity to collect data from enzyme-linked immunosorbent assays (ELISA)—used to detect and quantify substances, including antibodies, antigens, proteins, glycoproteins, and hormones—using urine samples from COVID-19 patients. I am also analyzing my data in order to correlate my results to clinical characteristics.
What's been the best part of your experience so far?
The best part of my experience has been learning new skills and collecting results that I am passionate about. I enjoy conducting my own experiments, collecting the data, and reflecting on what my results mean in the context of the project.
What impact do you hope this project makes once completed? How will this contribute to improving the health of women?
Once completed, I believe that this project will be the first of its kind in helping to elucidate the link between angiotensin-converting enzyme 2 (ACE2), kidney damage and how this may play into sex differences in COVID-19. Beyond the COVID-19 pandemic, understanding sex differences in ACE2 will have widespread implications for pathologies such as heart failure, where ACE2 is known to be protective.
What interested you in the WCHRI Summer Studentship Program?
I have always been passionate about women's health and was excited by the opportunity to contribute to this field on the research front. The WCHRI Summer Studentship Program allowed me to actively participate in a project that is important to me, and that I believe will have important impacts on our understanding of women's health.
What has the support from WCHRI and the Alberta Women’s Health Foundation meant to you?
The support from WCHRI and the Alberta Women's Health Foundation has meant that I am able to pursue this project and contribute to a field that is not well understood, despite the important implications it has for women's health. This support has not only furthered my own professional development but has allowed me to have a meaningful impact on a project I am passionate about.
Angiotensin-converting enzyme 2 (ACE2) is an enzyme that is widely expressed on cell surfaces throughout the human body, most notably in the kidneys, intestines, liver, heart and lungs. ACE2 is an important negative regulator of the renin-angiotensin system (RAS), which controls blood pressure and has been shown to be implicated in the development of cardiovascular disease. ACE2 is also the receptor for the cellular entry of SARS-CoV-2, the virus that causes COVID-19 infection. Following viral binding to ACE2, the complex is internalized into the cell and the expression of ACE2 is reduced via shedding from the membrane, possibly through the actions of the protease ADAM-17 (an enzyme that breaks down proteins and peptides).
The ACE2 gene is located on the X chromosome and escapes X-linked inactivation, meaning that females may harbour two active copies of the gene as opposed to males. It is possible that this plays a role in several sex differences noted between males and females in COVID-19 infection. Specifically, females exhibit lower mortality rates and are less likely to have severe disease resulting from COVID-19 infection. Interestingly, acute injury to the kidney is common in COVID-19 infection and is associated with a high mortality rate. Furthermore, there is evidence to suggest SARS-CoV-2 can directly infect kidney cells. Since ACE2 is highly expressed in kidney tissue, it is possible that renal damage in COVID-19 patients may manifest differently in male and female patients.
We hypothesize that sex differences in the renal effects of COVID-19 infection are critically dependent on differences in ACE2 mediated tissue protection. This project will evaluate kidney injury using MRI imaging, tissue pathology and characterization of ACE2 shedding from renal tissue in hospitalized and non-hospitalized patients of male and female sex. This work will be critical in determining the sex-specific effects of ACE2 expression in the context of COVID-19 renal injury. Overall, this project may contribute to our understanding of the mechanisms underlying sex differences by elucidating the effects of differential ACE2 expression.