Dr.
Krystal, Gerald
BSc, MSc, PhD (McGill)
Academic Ranks(s):
Professor, UBC, Distinguished Scientist
Affiliations(s):
Our lab is interested in both the effects of various diets on cancer (CA) incidence and in determining who is at risk of developing CA so we can prevent it by adopting life style changes. In regard to the first goal, since tumour cells are more dependent on blood glucose than normal cells for their growth, we have been testing low carbohydrate (CHO) diets on mice and found they reduce the incidence, growth rate and metastasis of primary tumours. Related to this, we have been studying ways to alter the properties of the immune cells within tumours to enhance their ability to kill the CA cells. Because many tumours secrete factors that subvert the ability of tumour-infiltrating immune cells to kill CA cells, we have been examining the effects of different immune modulating agents and found that low levels of non-steroidal anti-inflammatory drugs like Celebrex, in conjunction with our low CHO diets, dramatically reduce the growth rate of tumours.
In regard to the second goal, there is growing evidence that low levels of chronic inflammation (CI), i.e., below those manifesting in obvious disease, coupled with a poor immune response to viral infections increase the incidence of many human CAs. Thus the identification of individuals with low but detectable levels of CI and a poor anti-viral response would be of great value in indentifying high-risk people. As well, recent research has shown that what we eat determines the type of bacteria that reside in our gut (i.e., our gut microbiome) and these bacteria likely play an important role in determining our levels of CI. Lastly, macrophages (MФs), which are key immune cells in all our tissues, vary from person to person in their properties, from being skewed to very pro-inflammatory (M1 or killer MФs) in some people to very anti-inflammatory (M2 or healer MФs) in others, with most people being somewhere in between. Since MФs secrete many immune modulators, where on this spectrum a person’s MФs exist profoundly influences his/her level of CI and ability to fight off infections.
To explore all these areas further we have devised a series of simple tests in which very small amounts of whole human blood are both tested for markers of CI and incubated for 7 hours in the presence and absence of live bacteria and viruses to assess an individual’s immune response. As well, small fecal samples are analyzed to determine the bacterial makeup of our gut in order to relate the presence of specific bacteria with levels of CI to gain insight into which bacteria may be beneficial and which may be harmful. Ultimately, we hope to identify specific immune markers that can be used to predict an individual’s susceptibility to developing CA.
We are also interested in searching for nature-derived compounds that may be used to modulate our immune responses to prevent or treat CA and, lastly, since we have recently elucidated the factors in mouse blood that dramatically influence the skewing of MФs we would now like to determine if the same factors play a role in skewing human MФs. Identifying them would enable treatments to reduce CI and fight off infections and CA cells more effectively.
- Professor, Pathology & Laboratory Medicine, University of British Columbia (UBC)
- Member, Experimental Medicine, University of British Columbia (UBC)
- Member, Genetics, University of British Columbia (UBC)
Academic Background
- PhD, Biochemistry Dept. McGill University, Protein Chemistry. 1975
- MSc, Cancer Unit, McGill University, Enzymology. 1971
- BSc, McGill University, Biological Sciences. 1966
Awards and Recognition
Publications
Research Interest
- Blood research
- Immunology
- Inflammation
- Effect of diet on cancer
Our lab is interested in both the effects of various diets on cancer (CA) incidence and in determining who is at risk of developing CA so we can prevent it by adopting life style changes. In regard to the first goal, since tumour cells are more dependent on blood glucose than normal cells for their growth, we have been testing low carbohydrate (CHO) diets on mice and found they reduce the incidence, growth rate and metastasis of primary tumours. Related to this, we have been studying ways to alter the properties of the immune cells within tumours to enhance their ability to kill the CA cells. Because many tumours secrete factors that subvert the ability of tumour-infiltrating immune cells to kill CA cells, we have been examining the effects of different immune modulating agents and found that low levels of non-steroidal anti-inflammatory drugs like Celebrex, in conjunction with our low CHO diets, dramatically reduce the growth rate of tumours.
In regard to the second goal, there is growing evidence that low levels of chronic inflammation (CI), i.e., below those manifesting in obvious disease, coupled with a poor immune response to viral infections increase the incidence of many human CAs. Thus the identification of individuals with low but detectable levels of CI and a poor anti-viral response would be of great value in indentifying high-risk people. As well, recent research has shown that what we eat determines the type of bacteria that reside in our gut (i.e., our gut microbiome) and these bacteria likely play an important role in determining our levels of CI. Lastly, macrophages (MФs), which are key immune cells in all our tissues, vary from person to person in their properties, from being skewed to very pro-inflammatory (M1 or killer MФs) in some people to very anti-inflammatory (M2 or healer MФs) in others, with most people being somewhere in between. Since MФs secrete many immune modulators, where on this spectrum a person’s MФs exist profoundly influences his/her level of CI and ability to fight off infections.
To explore all these areas further we have devised a series of simple tests in which very small amounts of whole human blood are both tested for markers of CI and incubated for 7 hours in the presence and absence of live bacteria and viruses to assess an individual’s immune response. As well, small fecal samples are analyzed to determine the bacterial makeup of our gut in order to relate the presence of specific bacteria with levels of CI to gain insight into which bacteria may be beneficial and which may be harmful. Ultimately, we hope to identify specific immune markers that can be used to predict an individual’s susceptibility to developing CA.
We are also interested in searching for nature-derived compounds that may be used to modulate our immune responses to prevent or treat CA and, lastly, since we have recently elucidated the factors in mouse blood that dramatically influence the skewing of MФs we would now like to determine if the same factors play a role in skewing human MФs. Identifying them would enable treatments to reduce CI and fight off infections and CA cells more effectively.