Paul D. Goetsch

Biography

In multicellular organisms, how do multiple cell types originate from one cell and one genome? A critical early cell fate decision is whether to develop as germline (reproductive) or soma (non-reproductive). My research focuses on assessing how the highly conserved DREAM transcriptional repressor complex maintains the germ vs. soma cell fate decision during embryogenesis. After a flurry of cell divisions from the starting “germ cell” (i.e. united egg and sperm), somatic cells begin to exit the cell cycle as the DREAM complex suppresses the proliferative germ cell program. This process is commonly reverted in cancer cells (i.e. a soma-to-germline transition) and is intentionally reversed when mammalian somatic cells are reprogrammed into induced Pluripotent Stem Cells. DREAM’s involvement in protecting somatic cell differentiation suggests that transcriptional suppression of both “germness” and the cell cycle governs the establishment of cellular identity during development. A major challenge is identifying the transcription factors whose activities are unlocked following loss of DREAM function. To address this challenge, I have developed a functional genomics pipeline that integrates new CRISPR/Cas9 genome editing tools, high-throughput sequencing analysis, genetics, biochemistry, and cell biology in the Caenorhabditis elegans model system. Using this pipeline, my ongoing projects aim to elucidate how the DREAM complex forms and functions on chromatin, what transcription factors drive the soma-to-germline transition when DREAM function is lost, and how cellular quiescence is established. We will also apply our discoveries in C. elegans to help address how soma-to-germline transitions occur in cancer cells. Each project lays the groundwork for future work addressing how transcriptional events during development establish cellular identity.