Richard L. Carpenter, PhD

Metastasis, or the spread of tumors to other organs, plays a highly significant role in cancer biology considering that more than 90% of cancer deaths are attributable to metastasis. Metastasis is a complex, step-wise process whereby cells at a primary tumor site, such as the breast, gain the ability to leave the primary tumor and travel in the circulation to colonize in a new host organ, such as the brain. In order for cells to gain the ability to leave the primary tumor, the cell is reprogrammed by the resulting signaling pathways and activated transcription factors. Therefore, transcription factors sit at the nexus of cellular signaling pathways and genomic programs that alter the phenotype of the cell. We study the molecular mechanisms in cancer cells that regulate transcription factors and the subsequent genomic programs written by these transcription factors that lead to an altered phenotype. In particular, we are interested in the transcriptional programs that promote tumor progression and metastasis. In our lab, we utilize a wide breadth of techniques ranging from cell signaling with proteomics, to protein-DNA interactions, to RNA expression, and bioinformatic approaches to assess genomic programs by transcription factors. We also utilize multiple in vitro and in vivo models to assesss cell migration and invasion, tumor angiogenesis, tumor growth, and metastasis.

Heat shock factor 1 (HSF1) is one transcription factor we have discovered that plays a role in epithelial-to-mesenchymal transition (EMT) of breast cancer cells. EMT is a genetic program that alters the cells to a more mobile and invasive phenotype and is widely considered an early step in the process of metastasis. Our current work is investigating the mechanisms by which HSF1 promotes metastasis via EMT and cancer stem cell phenotypes, whether this pathway can be targeted to suppress metastasis, and identifying the gene signatures that occur when HSF1 is activated.

Truncated GLI1 (tGLI1) was discovered in 2009 and is an alternative splice variant of the GLI1 gene, the terminal transcription factor of the Sonic Hedgehog (Shh) signaling pathway. Truncated GLI1 has been shown to be exclusively expressed in cancer tissue but not healthy tissue, drives an aggressive cancer cell phenotype, and is a potent inducer of tumor angiogenesis. Our current work is investigating the mechanisms driving tGLI1-exclusive expression in tumor cells, the mechanisms by which tGLI1 promotes an invasive phenotype, and the gene programs induced by tGLI1 expression.