Wolfram goessling boston

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. Using chemical and genetic modulation, we assess organ formation, repair and carcinogenesis by in vivo imaging, functional genomic methods, and histological analysis to define the principal molecular and cellular mechanisms essential for organ growth.

Websites Lab Website. Nature cell biology. It is unclear, however, how Hippo signalling provides the cellular building blocks required for rapid growth. Here, we demonstrate that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 also known as YAP develop enlarged livers and are prone to liver tumour formation.

Transcriptomic and metabolomic profiling identify that Yap1 reprograms glutamine metabolism. Yap1 directly enhances glutamine synthetase glul expression and activity, elevating steady-state levels of glutamine and enhancing the relative isotopic enrichment of nitrogen during de novo purine and pyrimidine biosynthesis.

Genetic or pharmacological inhibition of GLUL diminishes the isotopic enrichment of nitrogen into nucleotides, suppressing hepatomegaly and the growth of liver cancer cells. Consequently, Yap-driven liver growth is susceptible to nucleotide inhibition. Together, our findings demonstrate that Yap1 integrates the anabolic demands of tissue growth during development and tumorigenesis by reprogramming nitrogen metabolism to stimulate nucleotide biosynthesis.

Cell stem cell. Pubmed: DOI:S 16 Hematopoietic stem and progenitor cell HSPC specification is regulated by numerous defined factors acting locally within the hemogenic niche; however, it is unclear whether production can adapt to fluctuating systemic needs.

Inhibition of neuronal, but not peripheral, tryptophan hydroxlyase Tph persistently reduced HSPC number. Our data establish that embryonic HSC production responds to physiologic stress via CNS-derived serotonin synthesis and central feedback regulation to control HSC numbers. Cannabinoid receptor signaling regulates liver development and metabolism.

Development Cambridge, England. By contrast, potential roles in organ development and embryonic energy consumption remain unknown.

Here, we demonstrate that genetic or chemical inhibition of cannabinoid receptor Cnr activity disrupts liver development and metabolic function in zebrafish Danio rerio , impacting hepatic differentiation, but not endodermal specification: loss of cannabinoid receptor 1 cnr1 and cnr2 activity leads to smaller livers with fewer hepatocytes, reduced liver-specific gene expression and proliferation.

Functional assays reveal abnormal biliary anatomy and lipid handling. Adult cnr2 mutants are susceptible to hepatic steatosis. Gastrointestinal Medical Oncology. He also serves as the Robert H. He is trained in both oncology and gastroenterology, and maintains a clinical practice focused on the treatment of patients with chronic liver disease and liver cancer. He actively teaches medical students as Director of the Introduction to Clinical Medicine course, and graduate students in the Developmental and Regenerative Biology program at Harvard Medical School.

Goessling is a physician-scientist, and his laboratory investigates molecular signals that regulate liver growth and metabolism during liver development, regeneration, and liver cancer formation. We utilize high-resolution spinning disc confocal imaging, single cell RNA-sequencing and organoid techniques to define the pathway and cellular determinants of organ growth.

The work in our laboratory is directly relevant for developing new treatment options for patients with chronic liver disease and liver cancer. Goessling is the Robert H. Goessling pursued his postdoctoral research with Dr. Leonard Zon at Children's Hospital, using zebrafish to characterize regulators of liver development, regeneration and cancer. Skip to main content.

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