Blobel Laboratory Research Overview

The Blobel lab studies fundamental mechanisms of gene regulation and epigenetics. Critical questions and topics that the team investigates include:

• How are genes and their regulatory elements spatially organized within the nucleus, and how does the 3D organization of the genome impact gene transcription and vice versa?
• How is the genome organized in terms of compartmentalization, domains, and regulatory loops? What are the factors that sculpt the spatial genome? What happens to the complex genome architecture every time a cell divides, or when a cell differentiates?
• How are gene expression programs epigenetically transmitted through cell division to maintain lineage identity, and how is the intricate genome organization faithfully rebuilt in daughter cell nuclei after every cell division?
• Which strategies will help us better understand the mechanisms of developmental control of the globin genes and how they relate to diseases affecting the globin genes such as sickle cell disease, the first known monogenic disease, and thalassemia?
  • For example, with our wonderful collaborators in Junwei Shi's group, we carry out extensive CRISPR-Cas9 and CRISPR-Cas12 screens to identify novel regulators of globin gene regulation that could serve as targets for pharmacological intervention for these diseases. Mechanistic studies aim to elucidate the mechanisms of action of these targets, and we study preclinical animal models to assess target relevance in vivo.
• How can transcription factors that are cancer dependencies mis-wire enhancers and promoters in T cells to cause malignancy?