Maya Bozzo-Rey (pictured left) is in her first year of McMaster University’s Master of Medical Sciences program after completing her undergraduate degree in Biology. During the 2024 Learning Pillar Week at St. Joseph’s Healthcare Hamilton, she won second place in the annual Research & Education Poster Competition. Maya’s research poster was titled “Exploring the Role of KDM6A as a Regulator of Proximal Tubular Epithelial Cell Dysmetabolism in Diabetic Kidney Disease.”
Maya’s research supervisor is Dr. Sergi Clotet-Freixas (pictured right), a basic scientist who has been at the Hamilton Centre for Kidney Research at St. Joe’s since 2023. He is also an assistant professor in the department of medicine at McMaster University and an affiliate scientist at The Research Institute of St. Joe’s Hamilton.
Dr. Clotet-Freixas led a study titled “Sex differences in kidney metabolism may reflect sex-dependent outcomes in human diabetic kidney disease,” which was published in Science Translational Medicine in 2024—Maya's research poster was based off results that were found in this study.
Diabetic Kidney Disease & Cellular Metabolism
Diabetic kidney disease (DKD) is a complication of diabetes that is characterized by a buildup of fibrotic tissue, or scarring, on the kidneys. This typically occurs when there is too much glucose in the bloodstream, such as in the case of diabetes. As DKD is the leading cause of kidney failure in North America, it can have life-threatening consequences.
Through studying DKD, Maya aims to help the scientific community better understand the complexities of diabetes as it has become more prevalent in recent years. By narrowing her scope of research to this single complication of diabetes, she hopes to make a significant difference in the lives of those experiencing it.
In Maya’s research poster, she demonstrated how rates of kidney cell metabolism are altered when the cells are challenged by high concentrations of glucose (to mimic diabetes). When kidney cells go through these metabolic alterations, the byproducts of this process can lead to fibrosis.
“Your mitochondria are a part of your cells that, when healthy, bring your cellular metabolism back to normal levels when they change,” said Maya. “However, in conditions like DKD, the mitochondria are constantly experiencing a certain level of stress, so they may not be able to restore the cell’s metabolism. This can result in permanent cell damage, or even cell death, which then leads to more fibrotic tissue on the kidneys.”
There are several epigenetic regulators in your body that work to change the amounts of certain enzymes, genes, and other factors within your kidney cells. By either inhibiting or activating these epigenetic regulators, certain treatments can manually adjust the levels of their related factors, potentially bringing cellular metabolism back to normal even in stressful conditions like DKD. One epigenetic regulator that is implicated in DKD is known as KDM6A.
KDM6A’s Role in Kidney Function
Studies have shown that inhibiting KDM6A in mice with high blood sugar (mimicking diabetes) is correlated with lower levels of damage to their kidneys’ glomeruli. The glomeruli are a vital part of the kidneys, as they function as tiny filtering units for waste and fluid.
Part of Maya’s research in Dr. Clotet-Freixas' lab is to investigate whether inhibiting KDM6A will also lead to more highly regulated metabolic rates in cells of another crucial kidney compartment, the proximal tubule; if so, this may provide an explanation for how the inhibition of KDM6A can help prevent or ameliorate proximal tubule damage and associated fibrosis in DKD. By further understanding the role of KDM6A in the kidneys, Maya and other DKD researchers aim to develop novel treatments that target its expression and help regulate cellular metabolism.
The next step in Maya’s research is to transition from growing kidney cells in a typical 2D cell culture to growing them in a 3D blood culture model. This part of Maya’s research will be conducted in collaboration with the team of Dr. Boyang Zhang (Chemical Engineering, McMaster University). Such a novel approach will allow her to view the cells in more detail and collect additional data that 2D models don’t show. For example, she will be able to look at the transport of glucose and other molecules coming in and out of the cells, and examine how these rates change with the inhibition of KDM6A.
Maya’s project has been recently funded externally by Diabetes Canada (January 2025-December 2027), and this support will enable Maya to continue addressing her important research questions in both 2D and 3D models of kidney cells.
Sex Differences in Cellular Metabolism
The KDM6A gene, which is responsible for levels of KDM6A proteins in the body, is encoded on the X chromosome (on the other hand, KDM6C is encoded on the Y chromosome). As such, levels of KDM6A proteins tend to be higher in females than males. Dr. Clotet-Freixas' lab is one of the first to examine the differences in these metabolic effects between males and females.
“The male metabolic profile has been studied for much longer than the female one,” said Maya. “Almost all relevant studies have been done on males. Through my research, I want to add a more diverse point of view.”
Through investigating these sex differences, Dr. Clotet-Freixas' lab aims to better understand how the development of DKD differs between males and females, which may lead to more effective treatments.
Mackensey Bacon (Manager, Innovation & Partnerships; left) presents the 2nd place award to Maya Bozzo-Rey (right) during our Celebrate Research 2024 ceremony.
St. Joe’s Commitment to Research Collaboration
At St. Joe’s, Maya has not only found valuable research opportunities, but also a supportive community that is ready to lend a hand whenever needed.
“Everyone here is so willing to collaborate and work in teams,” said Maya. “In other labs, the rooms can be very closed off from each other and you’re usually working on your own. That’s not the case at St. Joe’s so it’s very easy to collaborate. It’s amazing because if I ever have a question, there’s always someone who’s there to help.”
Although this is Maya’s first year as a researcher trainee at St. Joe’s, she has already accomplished a great deal in Dr. Clotet-Freixas' lab.
“We could not be more delighted with Maya’s team spirit, commitment, and work ethic,” said Dr. Clotet-Freixas. “In just a few months, she has immersed herself into a very complex project, and professionally presented new findings with a magnificent poster that gave her a very well-deserved second place.”