Dr. James B. Kirkland
Associate Professor
Email: jkirklan@uoguelph.ca
Office: ANNU 335
Ext: 56693
Lab: ANNU 325
Ext: 56693
Profile | Education | Research | Publications | Teaching | Grad Students | Lab Members | Links |
Profile
I did my PhD work here at the University of Guelph with Dr. Tammy Bray, who inspired me in the vast interface of nutrition and toxicology. My project involved a rumen tryptophan metabolite that was bioactivated by cytochrome P 450 enzymes in the lung, leading to a fatal respiratory disease. My interests in toxicology evolved through my postdoctoral experiences at the University of British Columbia and Universite Laval, eventually focusing on DNA damage and poly(ADP-ribose) metabolism. The mentorship of Dr. Guy Poirier at Laval was a major factor in my development, and he has been very supportive over the years in ongoing collaborations. My nutrition interests were a great fit with this project, as dietary niacin is required to make cellular NAD, which is the substrate for poly(ADP-ribose) synthesis. It has been my research goal over the past 15 years to identify the metabolic basis of pellagra, the human condition caused by dietary niacin deficiency. I have enjoyed working with many excellent students on these experiments. More recently, I have become more interested in food-borne carcinogens, especially those found in cooked meats, and how they interact with phytochemicals from vegetables. We are starting some research projects in this area, and I think there is a great potential to improve public health through improvements in meat processing. In my spare time, I enjoy kayaking, fishing, cycling and golf.
Education
B.Sc. - University of Guelph
Ph.D. - University of Guelph
Research
Niacin is a B vitamin that is involved in energy metabolism, but it also plays key roles in DNA repair and in signal transduction. Poly(ADP-ribose) is synthesized on proteins in response to DNA damage, using nicotinamide adenine dinucleotide (NAD) as substrate. Poly(ADP-ribose) synthesis is important in DNA repair and we are testing the effect of niacin deficiency on poly(ADP-ribose) synthesis, DNA repair rates, apoptosis and the progression of leukemia in response to carcinogen exposure. NAD and nicotinic acid are also used to make cyclic ADP-ribose and NAADP, two molecules that control the release of calcium from intracellular stores. Calcium release controls many aspects of cell signalling, and we are intersted in the processes of long term depression and potentiation that occur in brain neurons during the development of memory and learning. We are testing the effect of niacin deficiency and pharmacological supplementation on maze learning and brain metabolism.
Selected Publications
Tang, K., Sham, H., Hui, E. and Kirkland, J.B. Niacin deficiency causes oxidative stress in rat bone marrow cells, but not through decreased NADPH or glutathione status. J. Nutritional Biochemistry, in press.
Bartleman, A.P., Jacobs, R. and Kirkland, J.B. Niacin supplementation decreases the incidence of alkylation-induced non-lymphocytic leukemia in Long-Evans rats. Nutrition and Cancer, in press.
Kostecki, L.M., Thomas, M., Linford, G., Lizotte, M., Toxopeus, L., Bartleman, A.P. and Kirkland, J.B. Niacin deficiency delays DNA excision repair and increases spontaneous and nitrosourea-induced chromosomal instability in rat bone marrow. Mutation Research, in press.
Kirkland, J.B. Niacin status and genomic instability in bone marrow cells. Mechanisms favoring the progression of leukemogenesis. In; Water Soluble Vitamins (O. Stanger, ed.), Springer Verlag, in press.
Kirkland, J.B. Niacin. In: Handbook of Vitamins. Rucker RB, Zempleni J, Suttie JW, McCormick DB (eds), 4th edition. Taylor and Francis, Inc., Boca Raton, FL, pp 191-232 (2007).
Kirkland J.B., Zempleni J., Buckles L.K., Christman J.K. Vitamin-dependent modifications of chromatin: epigenetic events and genomic stability. In: Handbook of Vitamins. Rucker RB, Zempleni J, Suttie JW, McCormick DB (eds), 4th edition. Taylor and Francis, Inc., Boca Raton, FL, pp 521-544 (2007).
Kirkland, J.B. (2007) Phytochemicals, xenobiotic metabolism and carcinogenesis. In: Nutrient Drug Interactions (K.A. Meckling, Ed.), Taylor and Francis, Inc., Boca Raton, FL.
Thorn, S.L., Young, G.S. and Kirkland, J.B. (2007) The guinea pig is a poor animal model for studies of niacin deficiency and presents challenges in any study using purified diets. British J. Nutr., 98:78-85.
Spronck, J.C., Nickerson, J. and Kirkland, J.B. (2007) Niacin deficiency alters p53 expression and impairs etoposide-induced cell cycle arrest and apoptosis in rat bone marrow cells. Nutrition and Cancer, 57:88-99.
Young, G.S., Jacobson, E.L. and Kirkland, J.B. (2007) Water maze performance in young male Long-Evans rats is inversely affected by dietary intakes of niacin and may be linked to levels of the niacin metabolite cADPR. J. Nutr., 137:1050-1057.
Young, G.S. and Kirkland, J.B. (2007) Rat models of caloric intake and activity: relationships to animal physiology and human health. Applied Physiology, Nutrition and Metabolism, 32:161-176.
Young, G.S. and Kirkland, J.B. (2006) Modifications to increase the efficiency of the fluorimetric cycling assay for cyclic ADP-ribose. Combinat. Chem. & High Throughput Screening, 9:633-637.
Young, G.S., Choleris, E. and Kirkland, J.B. (2006) Use of salient and non-salient visiospatial cues by rats in the Morris Water Maze. Physiol. Behav. 87:794-799.
Young, G.S., Choleris, E., Lund, F. and Kirkland, J.B. (2006) Decreased cADPR and increased NAD+ in the Cd38-/- mouse. Biochem. Biophys. Res. Comm. 346:188-192.
Shah, G.M. , Shah, R.G., Veillette, H., Kirkland, J.B., Pasieka, J.L. and Warner, R.P. (2005) Biochemical assessment of niacin deficiency among carcinoid cancer patients. Amer. J Gastroenterol., 100:2307-2314.
Teaching
NUTR*4510 Toxicology, Nutriiton and Food
Grad Students
L. Delisle (MSc student)
L. Ip (PhD student)