Key Personnel:
Ramana V. Davuluri (PI)
Hematopoiesis is the process of the normal formation and development of blood cells, abnormalities in this developmental program lead to blood diseases including leukemia. These cancers account for nearly 10.3 percent of all deaths from cancer in recent years (Leukemia and Lymphoma Society). Despite the best attempts we only have cures for a small subset of these diverse hematologic cancers. From analysis of mice deficient in transcription factor (TF) genes and from the characterizations of chromosome breakpoints in human leukemias, it has become evident that altered transcriptional regulation is a major contributor to the neoplastic characteristics of most tumor cells. New technologies, such as DNA microarrays, are facilitating large-scale comparisons of gene expression in normal versus cancer cells. However, there are still many unanswered questions concerning the TFs that are altered in hematologic cancers, their target genes, and the mechanisms by which transcriptional regulation is achieved.
Consequently, the long-term goal of this project is to contribute to the understanding of the mechanisms in which hematopoietic-specific TFs and their combinatorial relationships regulate their target genes, resulting in either normal blood cell development or malignancy.
We have established an information resource of transcriptional regulation in hematopoiesis entitled HemoPDB: The Hematopoiesis Promoter Database, which may be accessed, in addition to further details, at http://bioinformatics.wistar.upenn.edu/HemoPDB. We are currently developing data mining tools to identify previously uncharacterized genes, and implementing statistical and pattern recognition models to infer the combinatorial relationship of these particular TFs. The information and tools resulting from this project will, hopefully, contribute to the elucidation of hematopoietic regulation on the genome level and identify the abnormalities, which disrupt this delicate balance.