The Andersson lab aims to understand how a multicellular organism, such as a human, develops specialized organs (a nervous system, a circulatory system, etc) from a single fertilized egg. As developmental biologists, we use mouse models, 3D cell culture, CRISPR cell lines, single cell omics, and patient samples to address fundamental questions with relevance for human health. For example, how are cellular proliferation and differentiation during embryogenesis coordinated with morphogenesis to achieve organs with the right function and shape to accomplish their jobs?
The liver is a highly versatile organ, with a shifting identity and function during embryogenesis and after birth. In the adult state, it is our largest internal organ and is responsible for hundreds of functions, from production of coagulation factors, and detoxification, to production of bile so we can digest fats and absorb fat-soluble vitamins. During embryogenesis, the liver is transiently composed of cells that will become liver cells, as well as cells that will become red and white blood cells. The embryonic liver has a well-developed tree of blood vessels that acts as a scaffold for development of the future bile duct system and is innervated by nerves whose cell bodies reside outside the liver. Thus, the embryonic liver is a nexus of cell types and organ systems, whose interaction during embryogenesis has not yet been fully understood. Deciphering the interaction of cell types and understanding the programs that lead to acquisition of the right cell fate, or establishment of the bile duct system, may allow us to design therapies or devise cures for the large number of diseases that affect the liver.
Alagille syndrome is a genetic disease usually caused by mutations in the gene JAG1, which encodes a ligand in the Notch signaling pathway. Children with this disease are often diagnosed when they have persistent jaundice (are yellow) after birth, revealing liver dysfunction due to an absence of well-developed bile ducts. Alagille syndrome also causes several other problems from heart defects to spontaneous bleeds. Our lab studies the role of Notch signaling in liver development, to better understand how bile ducts develop and in order to ultimately devise therapies for Alagille syndrome, and other diseases affecting the biliary system. Using a variety of technical approaches, as well as developing new methods when existing technology is insufficient, we aim to understand the interactions of Notch components in the embryonic liver, and decipher the interactions of liver cells with vasculature, hematopoietic cells and the nervous system during embryogenesis.
By resolving developmental principles, our aim is to develop therapies for congenital disorders, including Alagille Syndrome and neurodevelopmental disorders. In parallel, we are focused on devising high throughput gene-manipulation techniques to reduce the number of animals used in science, while improving the versatility and speed of scientific inquiry.