BBB seminar: Jane E. Johnson
Transcriptional control of neural development and cancer
Jane E. Johnson
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA
My laboratory uses the basic helix-loop-helix (bHLH) family of transcription factors to probe molecular mechanisms controlling the balance of neural progenitor cell maintenance and differentiation, and the generation of neuronal diversity. We have demonstrated that alterations in function and expression of the neural bHLH factors result in disturbances of neuronal connectivity, imbalances in excitatory and inhibitory neuron formation and loss of control of neural cell number. Much of our focus has been in the development of the dorsal spinal cord that is critical for somatosensory processing. Exploiting sequencing technologies and CRISPR, we continue to gain a deeper understanding of how transcription factors function by identifying direct transcriptional targets genome wide and connecting DNA binding factors to chromatin modifying events that modulate cell fate and plasticity. In addition, given neural bHLH factors, such as ASCL1, sit at critical choice points progenitor maintenance versus differentiation, it is not too surprising that some of these factors have functions in neural cancers. In particular, ASCL1 is present in multiple cancers including glioblastoma and neuroendocrine tumors in lung and prostate. Using leveraging reagents and mouse models generated from developmental studies, we are also addressing questions in cancer biology including cell of origin, tumor heterogeneity, and the requirement for developmental transcriptional regulators. Understanding how transcription factors regulate neuronal differentiation and diversity has direct implications for stem cell biology and cancer.
Chairperson: Nils Halberg, Department of Biomedicine