The applicant for this training fellowship has strong aspirations of becoming an academic investigator and educator and hopes to perform biomedical research in the areas of diet, nutrition and health. This fellowship application details the mentored training plan and the research project that are key components of the pre-doctoral training program to best prepare for such a career. The general scientific focus of the project is on the ability of, and mechanisms by which, a food product and their bioactive components may prevent cancer. Epidemiologic evidence suggests that consumption of a diet rich in cruciferous vegetables, particularly broccoli, is associated with a lower bladder cancer risk. Transitional cell carcinoma of the urinary bladder is the fifth most common neoplasm and the twelfth leading cause of cancer death in the United States. In addition, bladder cancer is estimated to be one of the most expensive cancers to treat with expenditures of over $3.7 billion annually. Cruciferous vegetables are phytochemical rich, and particularly have high concentrations of glucosinolates (GLUs) that are enzymatically hydrolyzed to bioactive isothiocyanates (ITCs) by myrosinase. There is growing evidence that isothiocyanates have anti-cancer activity. The central hypothesis of this application is that cruciferous vegetables, particularly broccoli, contain a phytochemical pattern that can inhibit bladder carcinogenesis.
We aim to test this hypothesis in precisely controlled in vitro and in vivo experimental model systems and to define biomarkers of activity and mechanism(s) of action. Our research plans are directed towards the following specific aims.
Specific Aim 1 : To test the hypothesis that broccoli and broccoli sprout diets can be efficiently absorbed, metabolized and distributed in an in vivo mouse model.
Specific Aim 2 : To test the hypothesis that broccoli and broccoli sprout diets can inhibit the progression of papillary bladder cancer in a transgenic mouse model.
Specific Aim 3 : To test the hypothesis that broccoli is able to inhibit papillary bladder cancer by inducing histone deacetylase inhibition and thereby modulating the Ha-ras signaling pathway. Bladder cancer's global burden is significant and necessitates the development of new strategies to prevent this disease. Ultimately, the goal of this application is to aid in the development of potent and novel functional foods for future use in human clinical trials, or alternatively dietary recommendations for cancer prevention in high risk individuals. In addition, through this work, the applicant will develop expertise in the fields of nutrition, cancer biology, experimental animal models, as well as acquire state-of- the-art technical skills in HPLC, molecular cell biology, animal modeling and histopathology. The mentoring program will instill critical thinking, expertise in experimental design and analysis, develop presentation and publication skills, and prepare the applicant for productive post-doctoral training and a bright future as an academic scientist.
Epidemiological studies demonstrate that consumption of a diet rich in cruciferous vegetables, particularly broccoli, is associated with a lower risk of bladder cancer. We propose to evaluate the absorption, metabolism and action of broccoli phytochemicals in pre-clinical models followed by studies of dietary prevention of bladder cancer in novel laboratory models. This research project is a component of the proposed pre-doctoral training program to develop the applicant for a future academic research career in the fields of diet, nutrition, and health.
|Abbaoui, Besma; Telu, Kelly H; Lucas, Christopher R et al. (2017) The impact of cruciferous vegetable isothiocyanates on histone acetylation and histone phosphorylation in bladder cancer. J Proteomics 156:94-103|
|Telu, Kelly H; Abbaoui, Besma; Thomas-Ahner, Jennifer M et al. (2013) Alterations of histone H1 phosphorylation during bladder carcinogenesis. J Proteome Res 12:3317-26|
|Abbaoui, Besma; Riedl, Kenneth M; Ralston, Robin A et al. (2012) Inhibition of bladder cancer by broccoli isothiocyanates sulforaphane and erucin: characterization, metabolism, and interconversion. Mol Nutr Food Res 56:1675-87|