Photo of Wolfram Goessling,  MD, PhD

Wolfram Goessling, MD, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-4704
Fax: (617) 525-4751


wgoessling@partners.org

Wolfram Goessling, MD, PhD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Health Sciences and Technology, Harvard Medical School
  • Associate Professor, Medicine, Harvard Medical School
  • Associate Physician, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute
  • Associate Physician, Medicine, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Developmental signaling pathways govern the formation and function of stem cells, thereby holding the key to unlocking the promise of adult tissue regeneration, and inhibiting cancer development. In our laboratory, we use zebrafish as the primary model to study organogenesis, regeneration and carcinogenesis. Our work focuses on the liver, where we explore the regulation of endodermal progenitor cell specification, organ differentiation and growth. We also examine the role of these pathways in zebrafish models of liver regeneration following both surgical and chemical injury, as well as in carcinogenesis. We are using mouse models to demonstrate evolutionary conservation and relevance for human biology.

Recently, we have shown that the wnt signaling pathway is an important regulator of liver development and liver regeneration. We found that prostaglandin positively interacts with and is required for wnt activity to exert its effect in these processes, offering a chance to therapeutically modify wnt-mediated stem and progenitor cell growth. In an effort to identify new regulatory pathways and genes important for liver development, we have initiated a genetic screen; to date we have identified several mutants with disturbed liver formation. In addition, we are proceeding with a chemical genetic screen, using a library of known biologics, to characterize signaling pathways relevant to liver growth. Among the initial set of compounds identified, one pathway has shown potential for regulating hepatic regeneration after injury and cancer progression. Prior work has shown us that we can translate our findings in the zebrafish to the bedside; we are currently planning the first clinical trial that originated from findings in the fish.

Publications

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  • Esain V, Kwan W, Carroll KJ, Cortes M, Liu SY, Frechette GM, Sheward LM, Nissim S, Goessling W, North TE. Cannabinoid Receptor-2 Regulates Embryonic Hematopoietic Stem Cell Development via Prostaglandin E2 and P-Selectin Activity. Stem Cells 2015; 33:2596-612. PubMed
  • Cox AG, Goessling W. The lure of zebrafish in liver research: regulation of hepatic growth in development and regeneration. Curr Opin Genet Dev 2015; 32:153-161. PubMed
  • McMahon GM, Olden M, Garnaas M, Yang Q, Liu X, Hwang SJ, Larson MG, , Goessling W, Fox CS. Sequencing of LRP2 Reveals Multiple Rare Variants Associated with Urinary Trefoil Factor-3. J Am Soc Nephrol 2014. PubMed
  • Carroll KJ, Esain V, Garnaas MK, Cortes M, Dovey MC, Nissim S, Frechette GM, Liu SY, Kwan W, Cutting CC, Harris JM, Gorelick DA, Halpern ME, Lawson ND, Goessling W, North TE. Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche. Dev Cell 2014; 29:437-53. PubMed
  • Nissim S, Sherwood RI, Wucherpfennig J, Saunders D, Harris JM, Esain V, Carroll KJ, Frechette GM, Kim AJ, Hwang KL, Cutting CC, Elledge S, North TE, Goessling W. Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth. Dev Cell 2014; 28:423-37. PubMed
  • Cutler C, Multani P, Robbins D, Kim HT, Le T, Hoggatt J, Pelus LM, Desponts C, Chen YB, Rezner B, Armand P, Koreth J, Glotzbecker B, Ho VT, Alyea E, Isom M, Kao G, Armant M, Silberstein L, Hu P, Soiffer RJ, Scadden DT, Ritz J, Goessling W, North TE, Mendlein J, Ballen K, Zon LI, Antin JH, Shoemaker DD. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 2013; 122:3074-81. PubMed
  • Liu LY, Fox CS, North TE, Goessling W. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development. Dis Model Mech 2013; 6:1271-8. PubMed
  • Shan J, Schwartz RE, Ross NT, Logan DJ, Thomas D, Duncan SA, North TE, Goessling W, Carpenter AE, Bhatia SN. Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat Chem Biol 2013; 9:514-20. PubMed
  • Wolpin BM, Ng K, Zhu AX, Abrams T, Enzinger PC, McCleary NJ, Schrag D, Kwak EL, Allen JN, Bhargava P, Chan JA, Goessling W, Blaszkowsky LS, Supko JG, Elliot M, Sato K, Regan E, Meyerhardt JA, Fuchs CS. Multicenter Phase II Study of Tivozanib (AV-951) and Everolimus (RAD001) for Patients With Refractory, Metastatic Colorectal Cancer. Oncologist 2013. PubMed
  • Harris JM, Esain V, Frechette GM, Harris LJ, Cox AG, Cortes M, Garnaas MK, Carroll KJ, Cutting CC, Khan T, Elks PM, Renshaw SA, Dickinson BC, Chang CJ, Murphy MP, Paw BH, Vander Heiden MG, Goessling W, North TE. Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo. Blood 2013; 121:2483-93. PubMed
  • Rosenbluh J, Nijhawan D, Cox AG, Li X, Neal JT, Schafer EJ, Zack TI, Wang X, Tsherniak A, Schinzel AC, Shao DD, Schumacher SE, Weir BA, Vazquez F, Cowley GS, Root DE, Mesirov JP, Beroukhim R, Kuo CJ, Goessling W, Hahn WC. 硫-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis. Cell 2012; 151:1457-73. PubMed
  • Garnaas MK, Cutting CC, Meyers A, Kelsey PB, Harris JM, North TE, Goessling W. Rargb regulates organ laterality in a zebrafish model of right atrial isomerism. Dev Biol 2012; 372:178-89. PubMed
  • Goessling W. Hepatic stellate cells and cirrhosis: Fishing for cures. Hepatology 2012; 56:1596-8. PubMed
  • Leshchiner I, Alexa K, Kelsey P, Adzhubei I, Austin-Tse CA, Cooney JD, Anderson H, King MJ, Stottmann RW, Garnaas MK, Ha S, Drummond IA, Paw BH, North TE, Beier DR, Goessling W, Sunyaev SR. Mutation mapping and identification by whole-genome sequencing. Genome Res 2012; 22:1541-8. PubMed
  • Shaik S, Nucera C, Inuzuka H, Gao D, Garnaas M, Frechette G, Harris L, Wan L, Fukushima H, Husain A, Nose V, Fadda G, Sadow PM, Goessling W, North T, Lawler J, Wei W. SCF(硫-TRCP) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2. J Exp Med 2012; 209:1289-307. PubMed
  • Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, Holm H, Sanna S, Kavousi M, Baumeister SE, Coin LJ, Deng G, Gieger C, Heard-Costa NL, Hottenga JJ, Kühnel B, Kumar V, Lagou V, Liang L, Luan J, Vidal PM, Leach IM, O'Reilly PF, Peden JF, Rahmioglu N, Soininen P, Speliotes EK, Yuan X, Thorleifsson G, Alizadeh BZ, Atwood LD, Borecki IB, Brown MJ, Charoen P, Cucca F, Das D, de Geus EJ, Dixon AL, Döring A, Ehret G, Eyjolfsson GI, Farrall M, Forouhi NG, Friedrich N, Goessling W, Gudbjartsson DF, Harris TB, Hartikainen AL, Heath S, Hirschfield GM, Hofman A, Homuth G, Hyppönen E, Janssen HL, Johnson T, Kangas AJ, Kema IP, Kühn JP, Lai S, Lathrop M, Lerch MM, Li Y, Liang TJ, Lin JP, Loos RJ, Martin NG, Moffatt MF, Montgomery GW, Munroe PB, Musunuru K, Nakamura Y, O'Donnell CJ, Olafsson I, Penninx BW, Pouta A, Prins BP, Prokopenko I, Puls R, Ruokonen A, Savolainen MJ, Schlessinger D, Schouten JN, Seedorf U, Sen-Chowdhry S, Siminovitch KA, Smit JH, Spector TD, Tan W, Teslovich TM, Tukiainen T, Uitterlinden AG, Van der Klauw MM, Vasan RS, Wallace C, Wallaschofski H, Wichmann HE, Willemsen G, Würtz P, Xu C, Yerges-Armstrong LM, , , , , , , , Abecasis GR, Ahmadi KR, Boomsma DI, Caulfield M, Cookson WO, van Duijn CM, Froguel P, Matsuda K, McCarthy MI, Meisinger C, Mooser V, Pietiläinen KH, Schumann G, Snieder H, Sternberg MJ, Stolk RP, Thomas HC, Thorsteinsdottir U, Uda M, Waeber G, Wareham NJ, Waterworth DM, Watkins H, Whitfield JB, Witteman JC, Wolffenbuttel BH, Fox CS, Ala-Korpela M, Stefansson K, Vollenweider P, Völzke H, Schadt EE, Scott J, Järvelin MR, Elliott P, Kooner JS. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet 2011. PubMed
  • Liu CT, Garnaas MK, Tin A, Kottgen A, Franceschini N, Peralta CA, de Boer IH, Lu X, Atkinson E, Ding J, Nalls M, Shriner D, Coresh J, Kutlar A, Bibbins-Domingo K, Siscovick D, Akylbekova E, Wyatt S, Astor B, Mychaleckjy J, Li M, Reilly MP, Townsend RR, Adeyemo A, Zonderman AB, de Andrade M, Turner ST, Mosley TH, Harris TB, , Rotimi CN, Liu Y, Kardia SL, Evans MK, Shlipak MG, Kramer H, Flessner MF, Dreisbach AW, Goessling W, Cupples LA, Kao WL, Fox CS. Genetic Association for Renal Traits among Participants of African Ancestry Reveals New Loci for Renal Function. PLoS Genet. 2011; 7:e1002264. PubMed
  • Saadi I, Alkuraya FS, Gisselbrecht SS, Goessling W, Cavallesco R, Turbe-Doan A, Petrin AL, Harris J, Siddiqui U, Grix AW, Hove HD, Leboulch P, Glover TW, Morton CC, Richieri-Costa A, Murray JC, Erickson RP, Maas RL. Deficiency of the cytoskeletal protein SPECC1L leads to oblique facial clefting. Am J Hum Genet 2011; 89:44-55. PubMed
  • Goessling W, Allen RS, Guan X, Jin P, Uchida N, Dovey M, Harris JM, Metzger ME, Bonifacino AC, Stroncek D, Stegner J, Armant M, Schlaeger T, Tisdale JF, Zon LI, Donahue RE, North TE. Prostaglandin e2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell 2011; 8:445-58. PubMed
  • North TE, Goessling W. Endoderm specification, liver development, and regeneration. Methods Cell Biol. 2011; 101:205-23. PubMed
  • Goessling W, North TE. Hematopoietic stem cell development: using the zebrafish to identify the signaling networks and physical forces regulating hematopoiesis. Methods Cell Biol. 2011; 105:117-36. PubMed
  • North TE, Babu IR, Vedder LM, Lord AM, Wishnok JS, Tannenbaum SR, Zon LI, Goessling W. PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury. Proc Natl Acad Sci U S A 2010; 107:17315-20. PubMed
  • Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, Zon LI, Armstrong SA. The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science 2010; 327:1650-3. PubMed
  • North TE, Goessling W. Previews. NOTCHing an arrow at cord blood: translating stem cell knowledge into clinical practice. Cell Stem Cell 2010; 6:186-7. PubMed
  • Baba Y, Nosho K, Shima K, Goessling W, Chan AT, Ng K, Chan JA, Giovannucci EL, Fuchs CS, Ogino S. PTGER2 overexpression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype. Cancer Epidemiol Biomarkers Prev 2010; 19:822-31. PubMed
  • Goessling W. Deciphering hepatocellular carcinoma: from bench to bedside and back. Gastroenterology 2009; 137:786-8. PubMed
  • Dovey M,Patton EE,Bowman T,North T,Goessling W,Zhou Y,Zon LI. Topoisomerase II alpha is required for embryonic development and liver regeneration in zebrafish. Mol Cell Biol 2009; 29:3746-53. PubMed
  • 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 2009; 137:736-48. PubMed
  • Goessling W,North TE,Loewer 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; 136:1136-47. PubMed
  • 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; 135:1935-44, 1944.e1. PubMed
  • 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; 27:5845-55. PubMed
  • Goessling W, North TE, Lord AM, Ceol C, Lee S, Weidinger G, Bourque C, Strijbosch R, Haramis AP, Puder M, Clevers H, Moon RT, Zon LI. APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development. Dev Biol 2008; 320:161-74. PubMed
  • 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; 2:183-9. PubMed
  • Goessling W, North TE, Zon LI. Ultrasound biomicroscopy permits in vivo characterization of zebrafish liver tumors. Nat Methods 2007; 4:551-3. PubMed
  • North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, Weber GJ, Bowman TV, Jang IH, Grosser T, Fitzgerald GA, Daley GQ, Orkin SH, Zon LI. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 2007; 447:1007-11. PubMed
  • Goessling W, North TE, Zon LI. New waves of discovery: modeling cancer in zebrafish. J Clin Oncol 2007; 25:2473-9. PubMed
  • Langenau DM, Keefe MD, Storer NY, Guyon JR, Kutok JL, Le X, Goessling W, Neuberg DS, Kunkel LM, Zon LI. Effects of RAS on the genesis of embryonal rhabdomyosarcoma. Genes Dev 2007; 21:1382-1395. PubMed
  • Goessling W, Mayer RJ. Systemic treatment of patients who have colorectal cancer and inflammatory bowel disease. Gastroenterol Clin North Am 2006; 35:713-27. PubMed
  • Goessling W, Friedman LS. Increased liver chemistry in an asymptomatic patient. Clin Gastroenterol Hepatol 2005; 3:852-8. PubMed
  • Goessling W, Chung RT. Amebic Liver Abscess. Curr Treat Options Gastroenterol 2002; 5:443-449. PubMed
  • Goessling W, McKee PH, Mayer RJ. Merkel cell carcinoma. J Clin Oncol 2002; 20:588-98. PubMed
  • Zucker SD, Goessling W, Bootle EJ, Sterritt C. Localization of bilirubin in phospholipid bilayers by parallax analysis of fluorescence quenching. J Lipid Res 2001; 42:1377-88. PubMed
  • Goessling W, Zucker SD. Role of apolipoprotein D in the transport of bilirubin in plasma. Am J Physiol Gastrointest Liver Physiol 2000; 279:G356-65. PubMed
  • Zucker SD, Goessling W. Mechanism of hepatocellular uptake of albumin-bound bilirubin. Biochim Biophys Acta 2000; 1463:197-208. PubMed
  • Zucker SD, Goessling W, Hoppin AG. Unconjugated bilirubin exhibits spontaneous diffusion through model lipid bilayers and native hepatocyte membranes. J Biol Chem 1999; 274:10852-62. PubMed
  • Zucker SD, Goessling W, Gollan JL. Intracellular transport of small hydrophobic compounds by the hepatocyte. Semin Liver Dis 1996; 16:159-67. PubMed
  • Zucker SD, Goessling W, Ransil BJ, Gollan JL. Influence of glutathione S-transferase B (ligandin) on the intermembrane transfer of bilirubin. Implications for the intracellular transport of nonsubstrate ligands in hepatocytes. J Clin Invest 1995; 96:1927-35. PubMed
  • Zucker SD, Goessling W, Gollan JL. Kinetics of bilirubin transfer between serum albumin and membrane vesicles. Insight into the mechanism of organic anion delivery to the hepatocyte plasma membrane. J Biol Chem 1995; 270:1074-81. PubMed
  • Zucker SD, Goessling W, Zeidel ML, Gollan JL. Membrane lipid composition and vesicle size modulate bilirubin intermembrane transfer. Evidence for membrane-directed trafficking of bilirubin in the hepatocyte. J Biol Chem 1994; 269:19262-70. PubMed
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