Exploratory Biology

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.

To sustain a multifunctional tissue, gastrointestinal stem cells divide constantly to replenish a broad spectrum of cell types. Two of its component cell types play an essential role in whole-body nutrient homeostasis: The nutrient-absorbing enterocytes and numerous types of hormone-producing enteroendocrine cells (EECs). These hormones affect important physiological processes related to metabolism, including peristaltic bowel movement and satiety. Our group studies how stem cells generate these diverse cell types, and how the intestine exerts its key metabolic functions. We employ a combination of engineered organoid systems, high-content CRISPR-based functional screens and single-cell technologies to tackle these questions.

The research group explores and expands 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.