Wolfram Goessling, MD, PhD
Office phone: 617-632-3474
Preferred contact method: office phone
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Area of ResearchGenetics causes of liver cancer and liver disease
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
- International Society for Stem Cell Research Travel Award, 2009
- William R. Hearst Young Investigator Award, Brigham and Womens Hospital, 2009
- Young Investigator Award: George Brecher Prize, International Society of Experimental Hematology, 2008
- New Investigator Award, Mount Desert Island, 2006-2007
- 29th Friends of Dana-Farber Cancer Institute Fellow, 2004-2005
- Noah T. Herndon and Irving Janock Fellowships in Gastrointestinal Cancer, 2003-2004
ResearchGenetics causes of liver cancer and liver disease
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.
- Goessling W: Deciphering hepatocellular carcinoma: from bench to bedside and back. Gastroenterology. 2009;137(3):786-8.
- Dovey M, Patton EE, BowmanT, North TE, Goessling W, Zhou Y, Zon LI. Topoisomerase II alpha is required for embryonic development and liver regeneration in zebrafish. Mol Cell Biol. 2009 Jul;29(13):3746-53.
- North TE*, Goessling W*, Peeters M, Li P, Ceol C, Lord AM, Harris J, Cutting CC, Huang P, Dzierzak E, Zon LI. Hematopoietic stem cell development is dependent on blood flow. Cell. 2009 May 15;137(4):736-48.
- 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 2009; 136(6):1136-47.
- 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. 2008; 135(6):1935-44
- 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. 2008; 27(44):5845-55.
- 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 2008; 320:161-174.
- 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 2008; 2: 183189.
- Goessling W, North TE, Zon LI. Ultrasound biomicroscopy permits in vivo characterization of zebrafish liver tumors. Nature Methods 2007; 4:551-3.