Dr. Alan Underhill is currently appointed as Associate Professor in the Division of Experimental Oncology in the Faculty of Medicine and Dentistry.
The Underhill laboratory is interested in deciphering how master regulators of melanocyte development contribute to melanoma pathogenesis. In addition, we are also examining how histone modifications regulate the balance between cell proliferation and differentiation, and how this is overridden in cancer.Project 1: Melanocyte transcription factors in melanoma
Malignant melanoma is one of the few cancers that continue to show an increase in incidence. The Underhill laboratory’s research focuses on the transcription factor PAX3, which is co-opted in malignant melanoma where it contributes to tumor
proliferation and survival. This same factor is required during embryonic development to specify and expand the melanocyte lineage and people with only one functional copy of PAX3 are characterized by pigmentary deficiencies. As a transcription factor, PAX3 regulates the expression of other genes and this is an essential facet of its role in melanoma. Nevertheless, the identity of these genes is largely unknown. A key goal of our research program is the identification of PAX3 target genes in melanoma, which will provide a molecular picture of a key gene network in melanoma pathogenesis.Project 2: Epigenetic control in cell differentiation and cancer
An essential component in the management and functional output of eukaryotic genomes is that their DNA is assembled into chromatin via the formation of nucleosomes, which comprise 147 bp of DNA wrapped nearly twice around an octamer of the core histone proteins H2A, H2B, H3, and H4 in equal stoichiometry. In addition to providing a means to compact the genome so that it fits within the nuclear confines, chromatin serves diverse roles in facilitating expression, repression and long-term silencing, replication, recombination, repair of damaged DNA, and mitosis. Over and above the regulatory information embedded in the genome, these different processes require a broad range of epigenetic controls that include chemical modification of DNA and histones, histone variants, linker histones and other chromatin architectural proteins, as well as the RNAi machinery. Within this scheme, our laboratory is examining how the methylation of lysine 20 on histone H4 modulates cell differentiation and how this process becomes aberrant in cancer.
We currently make extensive use of biochemical, genetic, molecular, cell-imaging, and computational approaches towards these ends. Research in the Underhill laboratory is supported by grants from the CIHR and ACRI, and Dr.
Underhill holds the Mary Johnston Chair in Melanoma Research.
Birth defects, pediatric cancer, gene regulation, Breast cancer, epigenetics, Melanoma, genetics, epigenetic, gene regulation, t