Developmental signaling pathways govern the formation and function of stem cells, thereby holding the key to unlocking the promise of adult tissue regeneration, and to inhibiting cancer development. In our laboratory, we use zebrafish as the primary model to study the liver and explore the regulation of endodermal progenitor cell specification, organ differentiation and growth. We then examine the conserved role of these signaling pathways in regulating tissue growth in surgical and chemical models of liver regeneration and genetic liver cancer models. We also use murine liver injury models to demonstrate evolutionary conservation and relevance for human disease. Our prior work has shown that we can translate our findings from the fish tank to the bedside, as the first clinical trial originating from our findings in the fish has begun to enroll patients.

We have found that the wnt pathway is an important regulator of liver development and regeneration. Recently, we showed that prostaglandin signaling interacts with wnt, offering a chance to therapeutically modify wnt-mediated stem and progenitor cell growth. In an effort to identify new pathways and genes important for liver development, we performed a genetic screen and characterized several mutants with disturbed liver formation. In addition, we are proceeding with a chemical genetic screen to characterize regulators of liver growth. We aim to use these findings and genomic analyses of clinical cohorts to better understand the interaction of regulatory signals that affect liver function and regeneration. The work in our laboratory is directly relevant for developing new treatment options for patients with liver failure and liver cancer.

Bio-Sketch

Dr. Goessling is an Assistant Professor of Medicine and of Health Sciences and Technology at Harvard Medical School. He received his MD and doctorate from the University of Witten/Herdecke in Germany. He trained in Internal Medicine at Brigham and Women's Hospital, served as Chief Medical Resident, and completed fellowship training in Hematology/Oncology at the combined Dana-Farber/Partners program and in Gastroenterology at Massachusetts General Hospital. Dr. Goessling pursued his postdoctoral research with Dr. Leonard Zon at Children’s Hospital, using zebrafish to characterize regulators of liver development, regeneration and cancer. He sees patients with liver disease and liver cancer at Dana-Farber Cancer Institute and Brigham and Women’s Hospital.

Website: http://fishing4stemcells.org

Selected Publications:

• Goessling W, North TE, Zon LI. New waves of discovery: modeling cancer in zebrafish. Journal of Clinical Oncology 25(17):2543-2549, 2007.
• Langenau D, Keefe M, Storer N, Guyon JR, Kutok JL, Le X, Goessling W, Neuberg D, Kunkel L, Zon LI. Effects of RAS on the genesis of embryonal rhabdomyosarcoma. Genes Dev. 21(11):1382-95, 2007
• North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, Weber GJ, Bowman TV, Jang I, Grosser T, FitzGerald GA, Daley GQ, Orkin SH, Zon LI. Prostaglandin E2 regulates vertebrate hematopoietic stem cell homeostasis. Nature 447:1007-11, 2007.
• Goessling W*, North TE*, Zon LI. Ultrasound biomicroscopy permits in vivo characterization of zebrafish liver tumors. Nature Methods 4:551-3, 2007.
• White RM, Sessa A, Burke C, Bowman T, LeBlanc J, Ceol C, Bourque C, Dovey M, Goessling W, Burns CE, Zon LI. Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell 2: 183–189, 2008.
• Goessling W, North TE, Ceol C, Lee S, Lord A, Weidinger G, Bourque C, Haramis AP, Puder M, Clevers H, Moon RT, Zon LI. APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development. Developmental Biology 320:161-174, 2008.
• Upadhyay G, Goessling W, North TE, Xavier R, Zon LI, Yajnik V. Molecular association between beta-catenin degradation complex and Rac guanine exchange factor DOCK4 is essential for Wnt/beta-catenin signaling. Oncogene 27(44):5845-55, 2008.
• Goessling W, Massaro JM, Vasan RS, D'Agostino RB, Ellison RC, Fox CS. Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease. Gastroenterology 135(6):1935-44, 2008
• Goessling W*, North TE*, Schmitt S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, Zon LI. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 136(6):1136-47, 2009.
• North TE*, Goessling W*, Peeters M, Li P, Ceol C, Lord AM, Weber GJ, Harris J, Cutting CC, Huang P, Dzierzak E, Zon LI. Hematopoietic stem cell development is dependent on blood flow. Cell 137(4):736-48, 2009.