Frank J Slack
Professor of Molecular, Cellular, and Developmental Biology
microRNA; aging; cancer biology; development; RNA; c. elegans
Development is a four-dimensional process, explicitly controlled by genes, that begins with fertilization and ends with death. We are using the advantages of the model organism C. elegans to find important genes and mechanisms that control developmental timing. A pathway of timing genes has been described by the identification of mutants where cells terminally differentiate at the wrong time relative to in wild-type animals. The temporal patterning pathway that is emerging includes key temporally expressed transcription factors and small, regulatory RNAs called microRNAs, with many of these genes related to human cancer genes. We are using molecular, genetic, and genomic approaches to understand the roles of the lin-4 and let-7 microRNAs, the LIN-14, LIN-42 and HBL-1 transcription factors, and the LIN-41 RING finger protein in the control of developmental timing and aging. An emerging theme is of universal patterning mechanisms acting throughout the animal kingdom. We are extrapolating our work to provide an understanding of how organs are specified at the correct time during development of higher animals. Our work should also lead to a better understanding of human cancer since cancer is often caused by the inappropriate adult redeployment of developmental pathways utilized previously in the embryo.
Extensive Research Description
Development, cancer and aging are intricately linked. Our lab focuses on using the advantages of C. elegans to find important genes and molecules that control aging and development of a stem cell pathway and testing if these genes are involved in aging, development and cancer in more complex organisms. A pathway of developmental timing genes, known as heterochronic genes has been identified through the genetic identification of C. elegans mutants that express stem cell fates either too early or too late relative to wild-type animals. This pathway controls the temporal progression of C. elegans development by regulating the abundance or activities of a succession of heterochronic genes over time, including key microRNAs. Since many of the C. elegans heterochronic genes and microRNAs control timing of cell differentiation and are related to human cancer genes, we are examining the role of their human homologues in cancer. We are also extrapolating our work in C. elegans to provide an understanding of how these genes and microRNAs regulate tissue differentiation and cell fate in mouse models. We are also developing microRNAs as cancer therapeutics. Lastly, since aging is the greatest risk factor for cancer, we are examining the roles of microRNAs in aging and longevity.