Young-In J. Kim, M.D., F.R.C.P.(C)

Professor Departments of Medicine & Nutritional Sciences Staff Gastroenterologist, Division of Gastroenterology, Department of Medicine, St. Michael's Hospital Keenan Research Centre Room 038, 16th floor Cardinal Carter Wing St. Michael’s Hospital 30 Bond Street Toronto, ON M5B 1W8 Tel: (416) 864 5848 Fax: (416) 978 8765 Email: youngin.kim@utoronto.ca

My research focuses on several aspects of nutrition and cancer including prevention, early detection and screening, molecular genetics and treatment using animal models, cell culture systems and human subjects.

Prevention

My laboratory is investigating how nutritional/dietary factors and potential chemopreventive agents can modulate the development of colon, breast, prostate and pancreatic cancers using animal models and human subjects. Using animal models and cell culture systems, my laboratory is investigating fundamental cellular and molecular mechanisms by which nutritional and dietary factors can modify the risk of cancer. A comprehensive mechanistic understanding of the preventive effect of nutritional and dietary factors is crucial in designing and implementing rational, effective and safe strategies for cancer prevention using these factors. Another area of cancer prevention research in my laboratory is the development of appropriate animal models of colon cancer by genetic engineering.

Early detection and screening

My group has been developing and validating potential cellular, molecular, epigenetic and biochemical markers of colon cancer that can be used as an endpoint of human prevention trials and as a predictor of colon cancer risk in humans. Eventually these potential biomarkers can be utilized as a screening tool to identify individuals at high risk of developing colon cancer for early diagnosis and aggressive preventive strategies. My group has also been evaluating special diagnostic technologies for identifying individuals harboring premalignant changes in the colon and those at high risk of developing colon cancer.

Molecular genetics

My laboratory has been investigating how subtle genetic variants called single nucleotide polymorphims in several key genes involved in the absorption, metabolism and excretion of nutrients and dietary factors modify colon cancer risk in animal and cell culture models. A comprehensive understanding of these molecular variants is essential in identifying individuals at risk of developing colon cancer for aggressive screening and preventive strategies. My group has also been examining how these molecular variants interact with nutrients and dietary factors in modifying colon cancer risk. The nutrient-gene interactions in the development and prevention of colon cancer is one of the most exciting and important emerging areas of colon cancer and nutrition research.

Treatment

My research also focuses on identifying and characterizing molecular and cellular markers (genetic variants in nutritional metabolic pathway) that can predict the response of colon cancer cells to chemotherapy using the state-of-the-art molecular biologic techniques in cell culture and animal models. This area of research is called "pharmacogenetics" and is important in providing safe and effective customized chemotherapy to patients with colon cancer by considering genetic variations in the metabolism of chemotherapeutic agents.

Nutrigenomics/Nutrigenetics

My research also focuses on clarifying differential expression patterns of genes that are involved in nutrition-mediated cancer development and treatment as well as on identifying novel gene(s) that are mechanistically related to these processes using gene expression profiling.

Relevant recent publications

1. Sohn KJ, Croxford R, Yates Z, Lucock M, Kim YI. Effect of the methylenetetrahydrofolate reductase C677T polymorphism on chemosensitivity of colon and breast cancer cells to 5-fluorouracil and methotrexate. The Journal of the National Cancer Institute 96: 134-144, 2004.
   
2. Sohn KJ, Smirnakis F, Moskovitz DN, Novakovic P, Yates Z, Lucock M, Croxford R, Kim YI. Effects of folylpolyglutamyl synthetase modulation on chemosensitity of colon cancer cells to 5-fluorouracil and methotrexate. Gut 2004 53: 1825-1831, 2004.
   
3. Stempak JM, Sohn KJ, Chiang EP, Shane B, Kim YI. Cell and stage of transformation specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model. Carcinogenesis 26, 981-990, 2005.
   
4. Kotsopoulos J, Medline A, Renlund R, Sohn KJ, Martin R, Hwang S, Lu S, Archer MC, Kim YI. Effects of dietary folate on the development and progression of mammary tumors in rats. Carcinogenesis 26: 1603-1612, 2005.
   
5. Bruce WR, Cirocco M, Giacca A, Kim YI, Marcon N, Minkin S. A pilot randomized controlled trial to reduce biomarkers associated with colorectal cancer risk - B vitamin deficiency, insulin resistance and colonic inflammation. British Journal of Cancer 93: 639-646, 2005.
   
6. Novakovic P, Stempak JM, Sohn KJ, Kim YI. Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis 27: 916-924, 2006.
   
7. Hayashi I, Sohn KJ, Stempak JM, Croxford R, Kim YI. Folate deficiency induces cell-specific changes in the steady-state transcript levels of genes involved in folate metabolism and one-carbon transfer reactions in human colonic epithelial cells. Journal of Nutrition 137: 607-613, 2007.
   
8. Kim YI. Will mandatory folic acid fortification prevent or promote cancer? American Journal of Clinical Nutrition 80: 1123-1128, 2004.
   
9. Kim YI. MTHFR polymorphisms and pharmacogenetics - A new role of single nucleotide polymorphisms in the folate metabolic pathway in human health and disease. Nutrition Reviews 63: 398-407, 2005.
   
10. Kim YI. Nutritional epigenetics: Impact of folate deficiency on DNA methylation and colon cancer susceptibility. Journal of Nutrition 135: 2703-2709; 2005.
    
11. Kim YI. Folate and colorectal cancer: An evidence-based critical review. Molecular Nutrition and Food Research 51: 267-292, 2007.