Exploratory Research

We use single-cell genomic, imaging, and stem cell bioengineering technologies to explore human development and disease. Broadly, we like to think about how cell fates and states are established during organ formation, how diverse cells organise themselves in complex microenvironments, and how disrupted cell ecosystems lead to disease. We use and develop high-information content measurements and computational methods to explore these topics. Currently we work primarily on development and disorders of the central nervous system and gastrointestinal tract. We are also interested in how human organs are different from other species, and how human evolution has led to disease susceptibilities.

We focus on adipose tissue biology, in particular how adipose tissue communicates with the central nervous system (CNS) and other tissues to mediate energy homeostasis. Findings may provide mechanistic insight on the pathophysiology of diabetes.

The development of CRISPR-mediated gene engineering has greatly expanded the scope and ease of generating accurate disease models. Yet, implementation of these tools in adult stem cell-derived organoids has proven to be technically challenging. The Organoid Gene Editing group develops new strategies to overcome existing technological bottlenecks and automate workflows. We employ next-generation CRISPR tools to generate complex isogenic disease models and confer synthetic features to organoids. These engineered organoids enable us to study cell fate specification in different epithelial tissues, as well as to explore the biology of rare intestinal cell types such as enteroendocrine cells.

The newly established research group will explore and expand upon Hans’ foundational work on growth conditions for organoids derived from adult epithelial stem cells. The main focus of the group will be on disease mechanisms that affect the human lung, liver and pancreas.