Sheila Teves

Our long-term goal is to understand the mechanisms governing transcriptional memory over multiple time scales. By focusing on the underlying mechanisms, we hope to generate models for how cells maintain self-identity over time, how cells change their identity over time, and how the next generation of the organism is borne from the old. These important questions touch on the cornerstone of multi-cellularity and propagation. From this goal, we have several ongoing research themes:

1. Mechanisms of Transcription Initiation

Our research explores how transcription initiation is regulated across different RNA polymerases. We focus on the TATA-box binding protein (TBP) and its role in transcription initiation for RNA Polymerases I, II, and III. We are particularly interested in understanding TBP-independent mechanisms that have emerged in multicellular organisms and how these alternative pathways influence gene regulation during development and stress responses.

2. Mechanisms of Transcriptional Memory

We investigate how cells "remember" their transcriptional state through multiple cell divisions. Our research examines the role of transcription factors in maintaining gene expression patterns. In particular, we are interested in the role of TFs like Sox2 as mitotic bookmarks and how this contributes to transcriptional memory in mammalian embryonic stem cells.

3. Evolutionary Forces Driving Conservation vs. Diversification in Transcription

Our work explores the evolutionary pressures that shape transcriptional machinery. We examine the divergence of Transcription factors across species and how these changes have influenced transcriptional regulation. By combining evolutionary genomics with functional assays, we aim to uncover how conserved and divergent mechanisms contribute to gene regulation in complex organisms.

4. Disease-Relevant Mutations in Transcription and Chromatin Proteins

Our research investigates how mutations in key transcription factors and chromatin regulators contribute to human disease. We focus on conditions such as neurodevelopment disorders, SOXopathies, atrial fibrillation, and hypertrophic cardiomyopathy. Through stem cell models and functional genomics, we aim to understand how these mutations disrupt normal gene regulation and identify potential therapeutic targets.

Mechanisms of Transcription Initiation

Our research explores how transcription initiation is regulated across different RNA polymerases. We focus on the TATA-box binding protein (TBP) and its role in transcription initiation for RNA Polymerases I, II, and III. We are particularly interested in understanding TBP-independent mechanisms that have emerged in multicellular organisms and how these alternative pathways influence gene regulation during development and stress responses.

Mechanisms of Transcriptional Memory

We investigate how cells "remember" their transcriptional state through multiple cell divisions. Our research examines the role of transcription factors in maintaining gene expression patterns. In particular, we are interested in the role of TFs like Sox2 as mitotic bookmarks and how this contributes to transcriptional memory in mammalian embryonic stem cells.

Evolutionary Forces Driving Conservation vs. Diversification in Transcription

Our work explores the evolutionary pressures that shape transcriptional machinery. We examine the divergence of Transcription factors across species and how these changes have influenced transcriptional regulation. By combining evolutionary genomics with functional assays, we aim to uncover how conserved and divergent mechanisms contribute to gene regulation in complex organisms.

Disease-Relevant Mutations in Transcription and Chromatin Proteins

Our research investigates how mutations in key transcription factors and chromatin regulators contribute to human disease. We focus on conditions such as neurodevelopment disorders, SOXopathies, atrial fibrillation, and hypertrophic cardiomyopathy. Through stem cell models and functional genomics, we aim to understand how these mutations disrupt normal gene regulation and identify potential therapeutic targets.