Date Completed: 1/14/09
Faculty Name: Trygve Tollefsbol
UAB Department: Biology
UAB School: Natural Sciences and Mathematics
Campus Address: CH 175
Campus Zip: 1170
Telephone: 934-4573
Email Address: trygve@uab.edu
Fax: 935-6097
Research Program Area: Cancer Chemoprevention
Project Title: Epigenetics of cancer prevention using green tea polyphenols
Project Status: Already up-and-running
Proposed Start Date: April 13
Proposed End Date: August 28
Number of Weeks of Internship: 16
Number of Interns: 1
Other faculty, staff, or graduate students who may help supervise intern: Tyson DeAngelis; Dr. Syed Meeran
Expected Number of Work Hours Per Week: 30 hours
Expected Work Schedule for Intern: Flexible, intern can largely set his or her own schedule
Number of Hours that you will personally supervise or work with the intern: 2
Category of Research: Laboratory Research
Cancer Research: Breast; Nutrition; Genetics
Project Description: Green tea is widely consumed as a popular beverage worldwide and has chemopreventive and anticancer properties. A major constituent of green tea is the polyphenol, epigallocatechin-3-gallate (EGCG), that is effective in the prevention of breast cancer, a leading cause of cancer-related deaths among females in the United States. Many studies have indicated that EGCG inhibits DNA methyltransferase 1 and telomerase activity which play critical roles in the progression of tumorgenesis. Telomerase inhibition by EGCG leads to apoptosis of cancer cells and oral administration of EGCG is effective especially in telomerase-expressing cancer cells. We discovered that EGCG down-regulates telomerase primarily through transcriptional control of the telomerase regulatory gene, hTERT, and other laboratories have now reported similar findings. Alterations of the hTERT gene by green tea polyphenols involve changes in histone acetylation, DNA methylation, and transcription factor binding although the roles of other epigenetic processes and the in vivo mechanisms are not fully understood. The main hypothesis is that green tea polyphenols prevent the epigenetic processes that lead to telomerase activation in breast cancer. A secondary hypothesis is that green tea modulates the availability of the histone deacetylases (HDACs), histone methyltransferases (HMTases), and/or DNA methyltransferases (DNMTs) as well as key transcription factors to the hTERT promoter leading to breast cancer prevention. Aim 1 will assess the role of green tea polyphenols in controlling histone methylation and acetylation at key residues known to be involved in hTERT regulation. Aim 2 will evaluate the interactions of te hTERT promoter with key epigenetic modulators such as the HDACs, HMTases, and DNMTs as well as major transcriptional regulators of hTERT. Aim 3 is to measure the in vivo effects of green tea polyphenols on epigenetic processes controlling the hTERT promoter using breast preclinical cancer prevention models. Since green tea has promise in reducing the incidence of breast cancer, the goal of this proposal is to determine the epigenetic mechanisms, both in vitro and in vivo, whereby this common dietary component decreases the incidence of breast cancer. It is intended that the outcome of these studies will facilitate more effective uses of green tea and/r polyphenols in cancer prevention and will help elucidate the mechanisms through which green tea imparts its chemopreventive properties.
Intern's Anticipated Duties:
Duty 1: Running gels
Duty 2: Preparing reagents
Duty 3: Analyzing data
Preceptor will provide intern with access to the following: office or desk space; computer and printer; laboratory work bench space; equipment needed to complete project; supplies needed to complete project
Likelihood of authoring publications: Possible
Background, education, experience, or expertise preferred: Biochemistry; Cell Biology; Basic Knowledge of Lab Skills; Nutrition Sciences; Molecular Biology
This faculty member has been a CaRES Preceptor for three or more summers.
Intern 1: OPEN