Heather Hook of the Siggers Lab is a recipient of the inaugural Kilachand Doctoral Fellowship. This fellowship is funded by the Multicellular Design Program (MDP), which combines research in Synthetic Biology, Microbial Engineering, Tissue Engineering, Data Science, and Biophysics to understand the design principles of multicellular systems.
Heather’s research is focused on developing a new high-throughput technique, termed CASCADE (Comprehensive Assessment of Complex Assembly at DNA Elements), to precisely profile the effects of single nucleotide variants on the indirect recruitment of transcriptional cofactors to DNA across different cell types and stimulus conditions. Using macrophage nuclear extracts, CASCADE has been used to map the determinants of constitutive and stimulus-dependent recruitment of cofactors to various enhancers and promoters of immune response genes. Furthermore, CASCADE has been used to characterize defective cofactor recruitment at known stimulus dependent GWAS single nucleotide variants (SNPs) implicated in immune diseases.
CASCADE will be used for Heather’s collaborative research project with the Mostoslavsksy lab of the Center of the Regenerative Medicine for her MDP fellowship. The goal of the project is to use CASCADE to identify transcriptional regulators controlling cell fate. Heather plans on following the development of induced pluripotent stem cells (iPSCs) to specific immune cells to identify transcriptional regulatory complexes governing developmental decisions. This work will help establish a new approach to understand and manipulate cellular fates that can be then be applied to more complex cellular differentiation systems.