Description:

Kristy Stengel, PhD - Assistant Professor, Department of Cell Biology, Albert Einstein College of Medicine

Abstract

Sequence-specific transcription factors are critical mediators of cellular response to both extracellular and intracellular cues. Rapidly changing transcriptional programs facilitate everything from cell fate decisions to stress responses, and the disruption of transcription factor function and/or expression is associated with disease states including cancer. While it is clear that the appropriate regulation of gene expression is critical for normal cellular function, historically, our ability to understand how sequence-specific transcription factors rapidly and specifically alter transcriptional programs has been limited by a toolbox of very slow genetic and knockdown strategies that take days to weeks before transcription factor activity can be assayed. Therefore, while direct transcriptional effects occur within minutes to hours, these models take days to establish, resulting in the detection of secondary and/or compensatory transcriptional changes that often mask the direct/immediate effects of transcription factor disruption. In order to overcome these technical limitations, we use CRISPR-mediated genome editing to introduce degron tags into endogenous transcription factor loci. This chemical-genetic approach results in rapid transcription factor degradation (minutes to hours) following PROTAC treatment, and effectively collapses the timeframe for assaying transcriptional changes, chromatin states, and genome-wide transcription factor occupancy from days to hours. Using this approach, we defined the mechanism of action of the RUNX1 transcription factor on gene regulation and enhancer function. We explore how this critical transcription factor sets the stage for appropriate myeloid development, and how disruption of RUNX1 function contributes to pathologic gene expression programs in myeloid leukemia.

About Kristy Stengel

Kristy Stengel completed her Ph.D. studies in Cell and Molecular Biology at the University of Cincinnati and Cincinnati Children’s Medical Center. After obtaining her Ph.D., Kristy pursued postdoctoral studies with Scott Hiebert at Vanderbilt University, where she was promoted to research assistant professor in 2017. In 2021, Kristy joined the faculty in the Department of Cell Biology at Albert Einstein College of Medicine as an assistant professor, where she continues her work using cutting edge technologies to define the mechanism of action of oncogenic transcription factors.

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