Amanda Poholek, PhD
- Assistant Professor, Department of Pediatrics
- Director, Health Sciences Sequencing Core
- Scholar, Richard King Mellon Foundation Institute for Pediatric Research
Education & Training
- Postdoctoral Fellow, National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, 2012-2015
- Postdoctoral Fellow, National Institutes of Health/National Institute of Allergy and Infectious Diseases, 2009-2011
- PhD in Cell Biology, Yale University, 2009
- BS in Biological Sciences, Fordham University, 2002
New technologies in genomic sequencing (NextGen technologies) have greatly increased our ability to study complex traits and assess how genetics and epigenetics contribute to health and disease. One application of genomic sequencing has been to understand cellular differentiation and identity, and how transcription factor networks control chromatin organization as well as transcriptomes. While some transcription factors function to directly activate genes, many also primarily function to change the accessibility of the chromatin, and create epigenetic changes that alter gene expression. My lab explores how the transcriptional repressors Bcl6 and Blimp-1 mediate changes in epigenetics that contribute to cellular differentiation of CD4 T cells, and how inappropriate epigenetic modifications may contribute to disease.
Blimp-1 and Bcl6 are expressed in a variety of cell types, most notably B cells, where they direct the differentiation of B cells into plasma cell or germinal center lineages, respectively. Both proteins function by binding to DNA and recruiting co-repressor complexes to mediate epigenetic changes that repress specific targets. Interestingly, Bcl6 and Blimp-1 can repress each other, indicating a carefully controlled transcriptional network exists wherein these two factors can shape cell fates in opposing ways. Projects in our lab work to understand what drives expression of Blimp-1 and Bcl6 in T cells, and how they modulate CD4 T cell function and identity. In addition, we are interested in understanding how these factors behave differently in different cell types.
- Exploring factors that contribute to Blimp-1 and Bcl6 expression in T cells
- Role of Blimp-1 and Bcl6 in altering the epigenetic landscape of CD4 T cells during differentiation
- Exploring the super enhancer structure of the Blimp-1 and Bcl6 locus.
- Exploring human SNPs in the Blimp-1 locus associated with disease via GWAS
- Understanding enhancer regions of the Blimp-1 and Bcl6 locus and how they control cell-type specific expression