On Dec. 30, three UHN physicians – Dr. Susan George, Dr. Michael Jewett and Dr. Heather Ross – were named to the Order of Canada, one of the country's highest civilian honours. UHN News is sitting down with each of them. Today, it's Dr. George.
Dr. Susan George is a clinical endocrinologist at Toronto General Hospital (TGH), and a Professor of Medicine and Pharmacology &Toxicology in the Temerty Faculty of Medicine at University of Toronto (U of T).
In conversation with Dr. Susan George
Q: How did you hear the news?
A: I was at home in a virtual meeting with my laboratory group and my cell phone rang with an unidentified caller, from area code 613. I did not answer the phone, so the person rang again but did not leave a message. Soon after, the house phone rang, which my husband answered, and he came in and said: "there is someone on the line who has to speak to you right away."
It was someone from the Governor General's office who gave me the news of my appointment. It was exciting and unexpected. I was deeply honoured and very grateful to be named.
Q: In your career, what drove your interest to the fields of molecular pharmacology and neuroendocrinology?
A: I have always been fascinated by and very interested in understanding how molecules like hormones and neurotransmitters signal in the body, and in the brain through proteins called receptors. When I was an Endocrinology Fellow at TGH, my mentor was Dr. Gerry Burrow, then Head of the Endocrine Division. We treated three patients with large pituitary tumors and impaired visual fields with a drug called bromocriptine and which demonstrated dramatic improvements in vision and regression of their tumors. We were among the first in the world to report this effect of bromocriptine – my first publication! I had the opportunity to present these results at a scientific meeting and it generated a huge amount of interest, and I was hooked!
On completion of my clinical training, I moved into the research laboratory to study dopamine receptors and how they function at a molecular level. In order to do this, I worked with Dr. Philip Seeman, a pioneer in the field of dopamine receptors, and we were part of the group that cloned several of the dopamine receptors. Dopamine receptors are present not just in the pituitary gland, but have very important functions in the brain to mediate the feeling of reward, locomotion, memory, learning etc., which have been the focus of my research.
Q: What is the work that you are most proud of, and why?
A: We study G protein coupled receptors – a family of proteins that act as molecular switches inside the cells – through which hormones and neurotransmitters communicate their signals – and their precise molecular mechanisms. We have identified several novel receptors, with novel mechanisms of action and established roles for these receptors in many physiological processes.
We also pioneered identification of a novel mechanism by which receptors form complexes and work cooperatively to generate unique signals. I am particularly proud of having discovered a novel dopamine receptor complex in the brain that appears to limit the reward mediated by dopamine and promotes aversion. This system is impacted in depression, anxiety, addiction, and contributes to the increased vulnerability of females to certain mood disorders and of adolescents to drug and other addictions.
The significance of these findings is that, once such mechanisms are explained and a role in disease processes identified, then screening for compounds that target these receptors to turn them on or off, forms the basis for pharmacological manipulations and has potential to lead to drug discovery.
Q: What is next for researchers studying dopamine receptors and their impact on mental health?
A: For our laboratory group, we are excited to continue to analyze the novel dopamine receptor complex we have identified, continue to examine human brain samples to establish changes in this receptor complex, especially in individuals with major depression, drug addiction and schizophrenia. We will continue with efforts for drug discovery, to provide the basis for pharmacological manipulations in pre-clinical models for study and potentially for medication development as there are big unmet needs for many of the above mental health disorders.
Q: What keeps you motivated, even during such challenging times as 2020 was for all of us?
A: The very exciting potential of studying the completely uncharted territory of a novel dopamine receptor complex in the brain that could have major implications for understanding the pathophysiology of several highly prevalent mental health disorders and provide insight into the sex differences and adolescent vulnerability of these conditions. The potential for developing drugs targeting this complex is also highly motivating.
Very importantly, the enthusiasm and dedication of my post-doctoral fellows and graduate students for this work is also a great factor that has kept all of us in the laboratory motivated, in spite of the challenges with work interruptions we all faced in 2020.
