Kristen L. Kroll, Ph.D., Associate Professor
Developmental Biology Program, Molecular Cell Biology Program
We are interested in understanding how embryonic and embryonic stem (ES) cells regulate self-renewal, lineage commitment, and differentiation and are studying these questions in the context of vertebrate neural development. Stepwise transcriptional cascades convert pluripotent embryonic cells into neurons: multipotent neural precursors form, commit to neuronal lineages, and then undergo cell cycle withdrawal and neuronal differentiation. We use ES, neural stem cell, and mouse models to study these processes.
A major focus of our work is on chromatin regulatory proteins, including the SWI-SNF and Polycomb complexes and the small nucleoprotein Geminin. These complexes critically regulate transcription to control self-renewal and differentiation in multiple cell contexts. They also regulate cell cycle progression and maintain genome integrity and their dysregulation is a pivotal aspect of multiple human malignancies.
Our current efforts include:
- Transcriptional regulatory networks controlling neural development. We are using genome-wide approaches to identify direct targets and regulated gene programs controlled by a group of transcription factors with major roles in neural precursor formation and neural tube patterning during early development.
- For a subset of these transcription factors, we are defining how loss of their activities disrupts neural development in mouse models and are assessing alterations in the neural transcriptional regulatory networks.
- We are also characterizing roles of several epigenetic regulators in controlling neural stem cell formation, maintenance, and differentiation, are using cell-based screening to define new epigenetic activities controlling these processes, and we are assessing contributions of altered epigenetic regulation to malignancy in medulloblastoma and glioblastoma.