Researchers in the making:
The liver and the immune system
McLeod Scholarship winner Braedon McDonald studies how white blood cells infiltrate organs to cause tissue damage.
Story by Laura Ly/Photos by Trudie Lee, Laughing Dog, and Martin Dee
White blood cells are the body's first line of defense against bacteria, viruses, and other foreign material. In disorders like sepsis, the cells go into overdrive and mount an attack against the body's own organs and tissues. Braedon McDonald, one of three winners of this year's Dr. Lionel E. McLeod Health Research Scholarship, studies the mechanisms of the immune system to determine why this occurs.
Sepsis is a life-threatening blood infection that is caused by the immune system's hyperactive and indiscriminate response to a bacterial infection. It is one of the top 10 causes of death in Alberta. "Sepsis is an interesting disease because it doesn't matter where the infection starts—whether it's in your abdomen from appendicitis or in your skin from a bacterial skin infection—the immune system attacks other parts of the body," explains McDonald. The disease causes a drop in blood pressure and can result in major organ failure. "That's a major focus of my research: to understand how and why the immune system is inappropriately activated during sepsis and why white blood cells infiltrate tissue like the liver to cause organ failure."
McDonald is particularly focused on how the liver is damaged during sepsis. "When immune cells accumulate in the liver, they begin to attack the liver, causing organ damage and potentially organ failure," explains McDonald. "Many liver diseases are caused when the immune system inappropriately attacks the body. As a result, my research can be applied to many different diseases that have an immunological component, such as hepatitis, or other types of infection."
He studies cell adhesion molecules—important molecules that allow white blood cells to accumulate in organs and tissue. "Adhesion molecules are substances that act as glue which help circulating immune cells stick to blood vessels and leave blood vessels to enter sites of infection," notes McDonald. "Our work has revealed that a cell adhesion molecule called CD44 plays an important role in allowing certain types of immune cells to interact and stick to the blood vessels in the liver."
McDonald's discovery could lead to new methods and drugs for treating liver disorders and immunological diseases like sepsis. "We found that, if you use different strategies to interrupt the binding of CD44 on immune cells, you can actually reduce the amount of white blood cells that get into the liver. This could have therapeutic benefits in limiting liver damage during sepsis," says McDonald.
McDonald's interest in research started in high school when he participated in the Heritage Youth Researcher Summer (HYRS) program run by the former Alberta Heritage Foundation for Medical Research (AHFMR)*. The HYRS program gives grade 11 students the opportunity to spend a summer in a university research lab in Alberta. "My HYRS experience planted the research seed for me. I spent a few summers working in Dr. Paul Kubes's lab as an undergraduate because I knew I enjoyed research. I then entered into the clinician scientist training program at the University of Calgary because I realized I wanted to conduct research as part of my career. Now I'm completing some of the research that I started in the Kubes lab."
*AHFMR is now Alberta Innovates – Health Solutions.
The McLeod scholarship
The Dr. Lionel E. McLeod Health Research Scholarship was established in memory of Dr. Lionel E. McLeod, founding president of AHFMR from 1981 to 1990. Dr. McLeod was also a former dean of Medicine at the University of Calgary, head of endocrinology at the University of Alberta, and the president and chief executive officer of the University Hospital in Vancouver. The McLeod scholarship has been awarded annually to an outstanding student at the University of Alberta, University of Calgary, or University of British Columbia for research related to human health. Along with Braedon McDonald, Patrick Stemkowski at the University of Alberta and Heidi Boyda at the University of British Columbia also received awards this year.
Patrick Stemkowski is currently pursuing a Ph.D. under the supervision of Dr. Peter Smith in the Department of Pharmacology, Faculty of Medicine and Dentistry at the University of Alberta. His research focuses on neuropathic pain resulting from injury to the nervous system. His work will provide new insight into the cause of this pain as well as a basis for the development of new treatments.
Heidi Boyda is currently pursuing a Ph.D. in the Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine at the University of British Columbia. Her research focuses on the metabolic side effects of antipsychotic drugs. More knowledge in this area could help provide better treatments for psychosis.