Research

Biology is amazingly complex, and yet only a minuscule fraction of possible cell states are found in nature. Our lab is investigating the full potential of cellular diversity and how it can be regulated.

At the heart of cell fate determination are transcription factors (TFs), the master regulators of gene expression. We are seeking to predict de novo TF activity in any cell, to perform intentional cell state transitions. This includes exploring uncharted regions in the landscape of cell states, e.g. transitions from diseased to healthy. Our research combines advanced mammalian cell culture models, genetic and epigenetic editing, single cell genomics, large-scale CRISPR screens, and various computational approaches to achieve this goal.

For more information, please visit our website: https://domcke.github.io/domcke-lab.html

TFs bind to specific DNA sequences, but only occupy a subset of potential sites in each cell type. We study the rules governing this cell type-specific binding and its effects.

We explore novel stable cell states that can be created with natural TFs. Mapping this opportunity landscape experimentally helps us train deep learning models to predict TF 'recipes' for intentional cell state transitions that do not occur in nature.

If we were able to predict cell state transitions in patients, this would unlock a new class of therapeutic strategies. To start bridging the gap between the dish and the clinic, we study transferability of our predictions from uni-cellular to multi-cellular systems, across environments and species.