Photo of Amy J. Wagers,  PhD

Amy J. Wagers, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 732-2590
Fax: (617) 732-2593


amy.wagers@joslin.harvard.edu

Amy J. Wagers, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Professor, Stem Cell and Regenerative Biology, Harvard Medical School
  • Investigator, Section on Developmental and Stem Cell Biology, Joslin Diabetes Center

DF/HCC PROGRAM AFFILIATION

Research Abstract

The broad interests of our lab relate to the identification and characterization of tissue-specific stem cell populations in adult animals, with particular emphasis on bone marrow-derived and blood-forming (hematopoietic) stem cells and skeletal muscle progenitors. In the hematopoietic system, we are particularly interested in defining regulators of hematopoietic stem cell migration and self-renewal and are pursuing genetic, genomic, and cell biological approaches to identifying genes and gene products that control the homing, mobilization, expansion, differentiation and survival of blood-forming stem cells in normal animals and in transplant settings. In addition, we have investigated potential mechanisms and determinants of bone marrow (BM) and hematopoietic stem cell lineage plasticity, using both transplantation and parabiotic mouse models in which the origin of engrafted cells can be traced via constitutive expression of green fluorescent protein (GFP). However, while some recent data had suggested that hematopoietic stem cells (HSC) may be capable of transdifferentiation, and thereby serve as a source of regenerative cells for the repair of both blood and non-blood tissues, thus far, we have found no evidence to support a significant contribution from hematopoietic or bone marrow sources to the regeneration of non-blood tissues. Instead, we find that in the rare instances in which we can detect contributions from BM or HSC to non-hematopoietic tissues, these events generally require significant tissue injury and occur by cell fusion, not transdifferentiation. Therefore, we have initiated additional studies to identify tissue-resident stem cell populations that function robustly to regenerate damaged adult tissues, and have recently succeeded in prospectively isolating, by fluorescence activated cell sorting (FACS), a novel population of adult skeletal muscle precursor cells with robust myogenic activity. Future studies in this area will be aimed at further defining cell lineage relationships in the differentiation of muscle stem and progenitor cells, as well as at identifying signaling pathways and gene expression programs important for maintaining these muscle-resident cell populations. In addition, we will apply similar isolation strategies to other adult tissues, including cardiac muscle and pancreas, to test the hypothesis that the adult tissues harbor as yet uncharacterized, isolatable stem cell populations that may support the repair of these tissues.

Publications

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  • Kim MJ, Miller CM, Shadrach JL, Wagers AJ, Serwold T. Young, proliferative thymic epithelial cells engraft and function in aging thymuses. J Immunol 2015; 194:4784-95. PubMed
  • Hettmer S, Bronson RT, Wagers AJ. Distinct malignant behaviors of mouse myogenic tumors induced by different oncogenetic lesions. 2015; 5:50. PubMed
  • Hettmer S, Li Z, Billin AN, Barr FG, Cornelison DD, Ehrlich AR, Guttridge DC, Hayes-Jordan A, Helman LJ, Houghton PJ, Khan J, Langenau DM, Linardic CM, Pal R, Partridge TA, Pavlath GK, Rota R, Schäfer BW, Shipley J, Stillman B, Wexler LH, Wagers AJ, Keller C. Rhabdomyosarcoma: current challenges and their implications for developing therapies. Cold Spring Harb Perspect Med 2014; 4:a025650. PubMed
  • Saez B, Ferraro F, Yusuf RZ, Cook CM, Yu VW, Pardo-Saganta A, Sykes SM, Palchaudhuri R, Schajnovitz A, Lotinun S, Lymperi S, Mendez-Ferrer S, Del Toro R, Day R, Vasic R, Acharya SS, Baron R, Lin CP, Yamaguchi Y, Wagers AJ, Scadden DT. Inhibiting stromal cell heparan sulfate synthesis improves stem cell mobilization and enables engraftment without cytotoxic conditioning. Blood 2014. PubMed
  • Tremblay AM, Missiaglia E, Galli GG, Hettmer S, Urcia R, Carrara M, Judson RN, Thway K, Nadal G, Selfe JL, Murray G, Calogero RA, De Bari C, Zammit PS, Delorenzi M, Wagers AJ, Shipley J, Wackerhage H, Camargo FD. The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation. Cancer Cell 2014; 26:273-87. PubMed
  • Oh J, Lee YD, Wagers AJ. Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nat Med 2014; 20:870-80. PubMed
  • Abraham J, Nuñez-Álvarez Y, Hettmer S, Carrió E, Chen HI, Nishijo K, Huang ET, Prajapati SI, Walker RL, Davis S, Rebeles J, Wiebush H, McCleish AT, Hampton ST, Bjornson CR, Brack AS, Wagers AJ, Rando TA, Capecchi MR, Marini FC, Ehler BR, Zarzabal LA, Goros MW, Michalek JE, Meltzer PS, Langenau DM, LeGallo RD, Mansoor A, Chen Y, Suelves M, Rubin BP, Keller C. Lineage of origin in rhabdomyosarcoma informs pharmacological response. Genes Dev 2014; 28:1578-91. PubMed
  • Hung CM, Calejman CM, Sanchez-Gurmaches J, Li H, Clish CB, Hettmer S, Wagers AJ, Guertin DA. Rictor/mTORC2 loss in the Myf5 lineage reprograms brown fat metabolism and protects mice against obesity and metabolic disease. Cell Rep 2014; 8:256-71. PubMed
  • Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, Chen JW, Lee RT, Wagers AJ, Rubin LL. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 2014; 344:630-4. PubMed
  • Hettmer S, Archer NM, Somers GR, Novokmet A, Wagers AJ, Diller L, Rodriguez-Galindo C, Teot LA, Malkin D. Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers. Cancer 2014; 120:1068-75. PubMed
  • Hettmer S, Teot LA, Kozakewich H, Werger AM, Davies KJ, Fletcher CD, Grier HE, Rodriguez-Galindo C, Wagers AJ. Myogenic Tumors in Nevoid Basal Cell Carcinoma Syndrome. J. Pediatr. Hematol. Oncol. 2014. PubMed
  • Lee JH, Bhang DH, Beede A, Huang TL, Stripp BR, Bloch KD, Wagers AJ, Tseng YH, Ryeom S, Kim CF. Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell 2014; 156:440-55. PubMed
  • Castiglioni A, Hettmer S, Lynes MD, Rao TN, Tchessalova D, Sinha I, Lee BT, Tseng YH, Wagers AJ. Isolation of Progenitors that Exhibit Myogenic/Osteogenic Bipotency In Vitro by Fluorescence-Activated Cell Sorting from Human Fetal Muscle. Stem Cell Reports 2014; 2:92-106. PubMed
  • Kikuchi K, Hettmer S, Aslam MI, Michalek JE, Laub W, Wilky BA, Loeb DM, Rubin BP, Wagers AJ, Keller C. Cell-cycle dependent expression of a translocation-mediated fusion oncogene mediates checkpoint adaptation in rhabdomyosarcoma. PLoS Genet. 2014; 10:e1004107. PubMed
  • Teo AK, Wagers AJ, Kulkarni RN. New opportunities: harnessing induced pluripotency for discovery in diabetes and metabolism. Cell Metab 2013; 18:775-91. PubMed
  • Xu C, Tabebordbar M, Iovino S, Ciarlo C, Liu J, Castiglioni A, Price E, Liu M, Barton ER, Kahn CR, Wagers AJ, Zon LI. A zebrafish embryo culture system defines factors that promote vertebrate myogenesis across species. Cell 2013; 155:909-21. PubMed
  • Aslam MI, Hettmer S, Abraham J, Latocha D, Soundararajan A, Huang ET, Goros MW, Michalek JE, Wang S, Mansoor A, Druker BJ, Wagers AJ, Tyner JW, Keller C. Dynamic and nuclear expression of PDGFR留 and IGF-1R in alveolar Rhabdomyosarcoma. Mol Cancer Res 2013; 11:1303-13. PubMed
  • Schepers K, Pietras EM, Reynaud D, Flach J, Binnewies M, Garg T, Wagers AJ, Hsiao EC, Passegué E. Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche. Cell Stem Cell 2013; 13:285-99. PubMed
  • Hettmer S, Teot LA, van Hummelen P, MacConaill L, Bronson RT, Dall'Osso C, Mao J, McMahon AP, Gruber PJ, Grier HE, Rodriguez-Galindo C, Fletcher CD, Wagers AJ. Mutations in Hedgehog pathway genes in fetal rhabdomyomas. J Pathol 2013; 231:44-52. PubMed
  • Le X, Pugach EK, Hettmer S, Storer NY, Liu J, Wills AA, Dibiase A, Chen EY, Ignatius MS, Poss KD, Wagers AJ, Langenau DM, Zon LI. A novel chemical screening strategy in zebrafish identifies common pathways in embryogenesis and rhabdomyosarcoma development. Development 2013. PubMed
  • Nabors LK, Wang LD, Wagers AJ, Kansas GS. Overlapping roles for endothelial selectins in murine hematopoietic stem/progenitor cell homing to bone marrow. Exp Hematol 2013. PubMed
  • Gazit R, Garrison BS, Rao TN, Shay T, Costello J, Ericson J, Kim F, Collins JJ, Regev A, Wagers AJ, Rossi DJ, . Transcriptome analysis identifies regulators of hematopoietic stem and progenitor cells. Stem Cell Reports 2013; 1:266-80. PubMed
  • Liu J, Hettmer S, Milsom MD, Hofmann I, Hua F, Miller C, Bronson RT, Wagers AJ. Induction of histiocytic sarcoma in mouse skeletal muscle. PLoS ONE 2012; 7:e44044. PubMed
  • Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, Apostolou E, Stadtfeld M, Li Y, Shioda T, Natesan S, Wagers AJ, Melnick A, Evans T, Hochedlinger K. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 2010; 28:848-55. PubMed
  • Young AP, Wagers AJ. Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors. J Cell Sci 2010; 123:2632-9. PubMed
  • Taylor PL, Barker RA, Blume KG, Cattaneo E, Colman A, Deng H, Edgar H, Fox IJ, Gerstle C, Goldstein LS, High KA, Lyall A, Parkman R, Pitossi FJ, Prentice ED, Rooke HM, Sipp DA, Srivastava A, Stayn S, Steinberg GK, Wagers AJ, Weissman IL. Patients beware: commercialized stem cell treatments on the web. Cell Stem Cell 2010; 7:43-9. PubMed
  • Schemionek M, Elling C, Steidl U, Baumer N, Hamilton A, Spieker T, Gothert JR, Stehling M, Wagers A, Huettner CS, Tenen DG, Tickenbrock L, Berdel WE, Serve H, Holyoake TL, Muller-Tidow C, Koschmieder S. BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells. Blood 2010; 115:3185-95. PubMed
  • Hettmer S, Wagers AJ. Muscling in: Uncovering the origins of rhabdomyosarcoma. Nat Med 2010; 16:171-3. PubMed
  • Mayack SR, Shadrach JL, Kim FS, Wagers AJ. Systemic signals regulate ageing and rejuvenation of blood stem cell niches. Nature 2010; 463:495-500. PubMed
  • Forsberg EC, Passegué E, Prohaska SS, Wagers AJ, Koeva M, Stuart JM, Weissman IL. Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic stem cells. PLoS ONE 2010; 5:e8785. PubMed
  • Guibal FC, Alberich-Jorda M, Hirai H, Ebralidze A, Levantini E, Di Ruscio A, Zhang P, Santana-Lemos BA, Neuberg D, Wagers AJ, Rego EM, Tenen DG. Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia. Blood 2009; 114:5415-25. PubMed
  • Mayack SR, Wagers AJ. Osteolineage niche cells initiate hematopoietic stem cell mobilization. Blood 2008; 112:519-31. PubMed
  • Breault DT,Min IM,Carlone DL,Farilla LG,Ambruzs DM,Henderson DE,Algra S,Montgomery RK,Wagers AJ,Hole N. Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells. Proc Natl Acad Sci U S A 2008; 105:10420-5. PubMed
  • Min IM, Pietramaggiori G, Kim FS, Passegue E, Stevenson KE, Wagers AJ. The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. Cell Stem Cell 2008; 2:380-91. PubMed
  • Jakubzick C, Tacke F, Ginhoux F, Wagers AJ, van Rooijen N, Mack M, Merad M, Randolph GJ. Blood Monocyte Subsets Differentially Give Rise to CD103+ and CD103- Pulmonary Dendritic Cell Populations. J Immunol 2008; 180:3019-27. PubMed
  • Laird DJ, von Andrian UH, Wagers AJ. Stem cell trafficking in tissue development, growth, and disease. Cell 2008; 132:612-30. PubMed
  • Massberg S, Schaerli P, Knezevic-Maramica I, Kollnberger M, Tubo N, Moseman EA, Huff IV, Junt T, Wagers AJ, Mazo IB, von Andrian UH. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell 2007; 131:994-1008. PubMed
  • Eggan K, Jurga S, Gosden R, Min IM, Wagers AJ. Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature 2006; 441:1109-14. PubMed
  • Sherwood RI, Wagers AJ. Harnessing the potential of myogenic satellite cells. Trends Mol Med 2006; 12:189-92. PubMed
  • Passegu. Regulating quiescence: new insights into hematopoietic stem cell biology. Dev Cell 2006; 10:415-7. PubMed
  • Wagers AJ, Weissman IL. Differential expression of alpha2 integrin separates long-term and short-term reconstituting Lin-/loThy1.1(lo)c-kit+ Sca-1+ hematopoietic stem cells. Stem Cells 2005; 24:1087-94. PubMed
  • Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 2004; 428:668-73. PubMed
  • Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell 2004; 116:639-48. PubMed
  • Christensen JL, Wright DE, Wagers AJ, Weissman IL. Circulation and chemotaxis of fetal hematopoietic stem cells. PLoS Biol 2004; 2:E75. PubMed
  • Cao YA, Wagers AJ, Beilhack A, Dusich J, Bachmann MH, Negrin RS, Weissman IL, Contag CH. Shifting foci of hematopoiesis during reconstitution from single stem cells. Proc Natl Acad Sci U S A 2003; 101:221-6. PubMed
  • Sherwood RI, Christensen JL, Weissman IL, Wagers AJ. Determinants of skeletal muscle contributions from circulating cells, bone marrow cells, and hematopoietic stem cells. Stem Cells 2004; 22:1292-304. PubMed
  • Kondo M, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF, Shizuru JA, Weissman IL. Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol 2003; 21:759-806. PubMed
  • Merad M, Manz MG, Karsunky H, Wagers A, Peters W, Charo I, Weissman IL, Cyster JG, Engleman EG. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol 2002; 3:1135-41. PubMed
  • Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002; 297:2256-9. PubMed
  • Wright DE, Bowman EP, Wagers AJ, Butcher EC, Weissman IL. Hematopoietic stem cells are uniquely selective in their migratory response to chemokines. J Exp Med 2002; 195:1145-54. PubMed
  • Wagers AJ, Christensen JL, Weissman IL. Cell fate determination from stem cells. Gene Ther 2002; 9:606-12. PubMed
  • Wagers AJ, Allsopp RC, Weissman IL. Changes in integrin expression are associated with altered homing properties of Lin(-/lo)Thy1.1(lo)Sca-1(+)c-kit(+) hematopoietic stem cells following mobilization by cyclophosphamide/granulocyte colony-stimulating factor. Exp Hematol 2002; 30:176-85. PubMed
  • Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL. Physiological migration of hematopoietic stem and progenitor cells. Science 2001; 294:1933-6. PubMed
  • Wright DE, Cheshier SH, Wagers AJ, Randall TD, Christensen JL, Weissman IL. Cyclophosphamide/granulocyte colony-stimulating factor causes selective mobilization of bone marrow hematopoietic stem cells into the blood after M phase of the cell cycle. Blood 2001; 97:2278-85. PubMed
  • Wagers AJ, Kansas GS. Potent induction of alpha(1,3)-fucosyltransferase VII in activated CD4+ T cells by TGF-beta 1 through a p38 mitogen-activated protein kinase-dependent pathway. J Immunol 2000; 165:5011-6. PubMed
  • Lim YC, Henault L, Wagers AJ, Kansas GS, Luscinskas FW, Lichtman AH. Expression of functional selectin ligands on Th cells is differentially regulated by IL-12 and IL-4. J Immunol 1999; 162:3193-201. PubMed
  • Wagers AJ, Waters CM, Stoolman LM, Kansas GS. Interleukin 12 and interleukin 4 control T cell adhesion to endothelial selectins through opposite effects on alpha1, 3-fucosyltransferase VII gene expression. J Exp Med 1998; 188:2225-31. PubMed
  • Wagers AJ, Stoolman LM, Craig R, Knibbs RN, Kansas GS. An sLex-deficient variant of HL60 cells exhibits high levels of adhesion to vascular selectins: further evidence that HECA-452 and CSLEX1 monoclonal antibody epitopes are not essential for high avidity binding to vascular selectins. J Immunol 1998; 160:5122-9. PubMed
  • Wagers AJ, Stoolman LM, Kannagi R, Craig R, Kansas GS. Expression of leukocyte fucosyltransferases regulates binding to E-selectin: relationship to previously implicated carbohydrate epitopes. J Immunol 1997; 159:1917-29. PubMed
  • Snapp KR, Wagers AJ, Craig R, Stoolman LM, Kansas GS. P-selectin glycoprotein ligand-1 is essential for adhesion to P-selectin but not E-selectin in stably transfected hematopoietic cell lines. Blood 1997; 89:896-901. PubMed
  • Wagers AJ, Lowe JB, Kansas GS. An important role for the alpha 1,3 fucosyltransferase, FucT-VII, in leukocyte adhesion to E-selectin. Blood 1996; 88:2125-32. PubMed
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