Key Personnel:
Ramana V. Davuluri (PI)
Tim Huang (Co-I)
Hao Sun, Research Scientist
Sandya Liyanarachichi, Statistics Specialist
Complementary to the NIH R01 (sponsored by NHGRI) research investigation is the role of alternative promoters in cancer progression. There is growing evidence linking aberrant use of multiple promoters and cancer formation: several oncogenes and tumor-suppressor genes (e.g., MYC, CYP19, BRCA1, P73, MID1, Cathespin B, SRC, kallikrien 6 and TGF- 3) have multiple promoters, and moreover, the aberrant preference of one promoter over another in some of these genes is directly linked to cancerous cell growth. We rationalize that the regional epigenetic modifications in alternative promoters are tissue-specific and that disruptions to these processes occur during cancer initiation and progression. These abnormal events may lead to the eventual silencing or activation of critical promoters of cancer genes. We hypothesize that regional epigenetic deregulation of one promoter over another alters the transcriptional profile of the target gene, resulting in the initiation and promotion of neoplastic outgrowth of cancer cells. We use a combination of computational, statistical and high-throughput experimental (ChIP-chip) approaches to study and model the use of alternative promoters of human genes in cancer cells. This new paradigm will lead to improved biomarkers and drug discovery for cancer treatment. This research is supported by a four year research scholar grant (RSG-06-268-01) awarded by American Cancer Society.
In order to integrate the immense amount of available data, we have developed
an efficient data-mining pipeline that integrates important details about
several gene promoters and the expression pattern of corresponding genes
with the genome sequences. We have deposited all this information in a database
composed of a genome-wide map of mammalian promoters and first exons, entitled
MPromDb: The Mammalian Promoter Database. Additional information and access
to the user-friendly web interface may be accessed from:
http://bioinformatics.wistar.upenn.edu/MPromDb.
Sponsored by: American Cancer Society