Chronic liver disease is a common cause of death in the United States, and liver cancer incidence is growing faster than that of any other cancer. The Goessling laboratory seeks to understand the mechanisms that cause organ injury and the signals that regulate regenerative and malignant growth. Our specific interests are to define the similarities in important signaling pathways between development, regeneration and carcinogenesis of the liver, an important organ for the organism’s metabolism and protein synthesis with remarkable regenerative capacities. We investigate zebrafish as the primary model to discover novel regulatory pathways of liver development and evaluate their importance for recovery after toxic and physical injury, complemented by mouse models and organoids derived from human cell samples. Using chemical and genetic screens and targeted genetic modulation, we assess organ formation, repair and carcinogenesis by high-resolution in vivo imaging, single-cell and functional genomic methods, and other phenotype analyses to define the principal molecular and cellular mechanisms regulating organ growth.
Our goal is to develop novel therapeutic approaches for patients with liver failure and cancer. To this end, we have a number of exciting projects ongoing in the lab exploring liver development, disease and regeneration, using zebrafish, mouse and human models:
- Arkadi Shwartz and Yujin Moon focus on studying the role of macrophages in liver development and regeneration, utilizing various cell ablation strategies, transgenic reporters of different liver cell types, and live imaging techniques to dynamically monitor the liver-macrophage interaction in health and diseases.
- Isaac Oderberg uses a combination of single-cell sequencing, in vivo lineage tracing, histology as well as pharmacological and genetic perturbations to study cell-fate transitions during liver regeneration in adult zebrafish.
- Lauren Snow is developing a model of alcoholic liver disease in adult zebrafish.
- Through the use of 3D in vitro models, Brian Pepe-Mooney and Colton Smith aim to further our understanding of the cellular interactions that occur in heterogeneous tissues and elucidate the mechanisms that drive liver cancers and other metabolic diseases.
- Marc Sherman and Carolyn Winston use single-cell sequencing, single-molecule FISH, and mouse models to study nonalcoholic fatty liver disease.
- Titus Butzlaff uses immunohistochemistry to discover early markers of NAFLD and NASH.
- Using the zebrafish model and clinic cohorts, Olivia Weeks interrogates the mechanisms underlying ethanol's teratogenicity and identifies the implications of prenatal alcohol exposure on adult metabolic health outcomes.
- Manjari Trivedi is exploring the role of leukocytes in liver regeneration and fibrosis.
- Scott Freeburg uses transgenesis, CRISPR, confocal microscopy, and RNA-sequencing to investigate the functions of Vitamin D Receptor in embryonic liver formation, adult liver metabolism, and liver disease.
- Bess Miller uses genetic and chemical tools to study the role of the proteasome on development.