James Amatruda, MD, PhD
James F. Amatruda, MD, PhD is the Chief of the Division of Pediatric Hematology-Oncology, Director of the Cancer and Blood Disease Institute (CBDI), and the Alfred E. Mann Family Foundation Chair in Cancer Research at Children’s Hospital Los Angeles (CHLA). He is also tenured Professor of Pediatrics and Medicine at the USC Keck School of Medicine and the Associate Director for Pediatric Oncology in the USC Norris Comprehensive Cancer Center. He received his Bachelor’s degree in Biochemical Sciences from Harvard University and his MD, PhD from Washington University School of Medicine. He did internship and residency training in Internal Medicine at the Brigham and Women’s Hospital in Boston, MA, followed by fellowship training in Medical Oncology at Dana-Farber/Partners Cancer Care in Boston, MA. He was a Postdoctoral Fellow in the laboratory of Dr. Leonard Zon at Boston Children’s Hospital, Harvard Medical School. From 2005-2019, Dr. Amatruda was on the faculty of UT Southwestern Medical Center in Dallas, TX.
Dr. Amatruda is a physician-scientist with a primary research and clinical focus on solid tumors of childhood including sarcomas, germ cell tumors and Wilms tumor. His lab has developed zebrafish models of genetic subtypes of pediatric solid tumors to better define their biology and to use that knowledge to identify and validate novel approaches for improved therapies. He has had long-standing leadership positions in the Children’s Oncology Group; serving as Chair for the Germ Cell Tumor Biology Committee and the Rare Tumors Biology Committee. Dr. Amatruda is an Editor of the journal Disease Models & Mechanisms. He also serves on the Scientific Advisory Boards of the William Guy Forbeck Foundation, the Sam Day Foundation, the Pablove Foundation, and Curing Kids Cancer.
Solid tumors of childhood including sarcomas, germ cell tumors and Wilms tumor
Education
Washington University School of Medicine, St. Louis, MO
PhD, Cell Biology, Washington University School of Medicine, St. Louis, MO
Internal Medicine, Brigham and Women’s Hospital, Boston, MA
Internal Medicine, Brigham and Women’s Hospital, Boston, MA
Visiting Fellow, Institute of Cell Biology, Consiglio Nazionale delle Ricerche, Rome, Italy
Fellow, Medical Oncology, Dana-Farber/Partners Cancer Care, Boston, MA
Postdoctoral Fellow, lab of Dr. Leonard Zon, Boston Children’s Hospital, Boston, MA
Accomplishments
Internal Medicine
Medical Oncology
American Society for Pediatric Hematology-Oncology
Children's Oncology Group
American Association for Cancer Research
Zebrafish Disease Models Society
Scholar Award, William Guy Forbeck Foundation
Horchow Endowed Scholar in Pediatrics, UT Southwestern Medical Center
Outstanding Pre-Clinical Teacher, 1st- year Medical School Class, UT Southwestern Medical Center
Keynote Speaker, MS1 Orientation Weekend, UT Southwestern Medical Center
Health Care Heroes Award, Academic Researcher, Dallas Business Journal
Regent's Outstanding Teaching Award, University of Texas System
Pediatric Residency Faculty Teaching Award, Children’s Hospital Los Angeles
Publications
Singla, N., Lafin, J.T., Ghandour, R.A., Kaffenberger, S., Amatruda, J.F., and Bagrodia, A. (2019). Genetics of testicular germ cell tumors. Curr Opin Urol 29, 344-349. Pubmed: 31045925
Sanchez, A., Xu, L., Pierce, J.L., Lafin, J.T., Abe, D., Bagrodia, A., Frazier, A.L., and Amatruda, J.F. (2019). Identification of testicular cancer driver genes by a cross-species comparative oncology approach. Andrology 7, 545-554. Pubmed: 31087453
O'Neill, A.F., Xia, C., Krailo, M.D., Shaikh, F., Pashankar, F.D., Billmire, D.F., Olson, T.A., Amatruda, J.F., Villaluna, D., Huang, L., et al. (2019). alpha-Fetoprotein as a predictor of outcome for children with germ cell tumors: A report from the Malignant Germ Cell International Consortium. Cancer. Pubmed: 31355926
Lafin, J.T., Bagrodia, A., Woldu, S., and Amatruda, J.F. (2019). New insights into germ cell tumor genomics. Andrology 7, 507-515. Pubmed: 30896089
Fonseca, A., Xia, C., Lorenzo, A.J., Krailo, M., Olson, T.A., Pashankar, F., Malogolowkin, M.H., Amatruda, J.F., Billmire, D.F., Rodriguez-Galindo, C., et al. (2019). Detection of Relapse by Tumor Markers Versus Imaging in Children and Adolescents With Nongerminomatous Malignant Germ Cell Tumors: A Report From the Children's Oncology Group. J Clin Oncol 37, 396-402. Pubmed: 30576269
Bhakta, M., Padanad, M.S., Harris, J.P., Lubczyk, C., Amatruda, J.F., and Munshi, N.V. (2019). pouC Regulates Expression of bmp4 During Atrioventricular Canal Formation in Zebrafish. Dev Dyn 248, 173-188. Pubmed: 30444277
Xu, L., Zheng, Y., Liu, J., Rakheja, D., Singleterry, S., Laetsch, T.W., Shern, J.F., Khan, J., Triche, T.J., Hawkins, D.S., et al. (2018). Integrative Bayesian Analysis Identifies Rhabdomyosarcoma Disease Genes. Cell Rep 24, 238-251. Pubmed: 29972784
Woldu, S.L., Moore, J.A., Ci, B., Freifeld, Y., Clinton, T.N., Aydin, A.M., Singla, N., Laura-Maria, K., Hutchinson, R.C., Amatruda, J.F., et al. (2018a). Practice Patterns and Impact of Postchemotherapy Retroperitoneal Lymph Node Dissection on Testicular Cancer Outcomes. Eur Urol Oncol 1, 242-251. Pubmed: 31058267
Woldu, S.L., Aydin, A.M., Rao, A.V., Hutchinson, R.C., Singla, N., Clinton, T.N., Krabbe, L.M., Passoni, N.M., Raj, G.V., Miller, D.S., et al. (2018b). Differences at Presentation and Treatment of Testicular Cancer in Hispanic Men: Institutional and National Hospital-based Analyses. Urology 112, 103-111. Pubmed: 29079210
Williams, L.A., Pankratz, N., Lane, J., Krailo, M., Roesler, M., Richardson, M., Frazier, A.L., Amatruda, J.F., and Poynter, J.N. (2018a). Klinefelter syndrome in males with germ cell tumors: A report from the Children's Oncology Group. Cancer 124, 3900-3908. Pubmed: 30291793
Williams, L.A., Mills, L., Hooten, A.J., Langer, E., Roesler, M., Frazier, A.L., Krailo, M., Nelson, H.H., Bestrashniy, J., Amatruda, J.F., et al. (2018b). Differences in DNA methylation profiles by histologic subtype of paediatric germ cell tumours: a report from the Children's Oncology Group. Br J Cancer 119, 864-872. Pubmed: 30287918
Stoneham, S.J., Hale, J.P., Rodriguez-Galindo, C., Dang, H., Olson, T., Murray, M., Amatruda, J.F., Thornton, C., Arul, G.S., Billmire, D., et al. (2018). Adolescents and Young Adults With a "Rare" Cancer: Getting Past Semantics to Optimal Care for Patients With Germ Cell Tumors. Oncologist 23, 272. Pubmed: 29449513
Shah, R., Xia, C., Krailo, M., Amatruda, J.F., Arul, S.G., Billmire, D.F., Brady, W.E., Covens, A., Gershenson, D.M., Hale, J.P., et al. (2018). Is carboplatin-based chemotherapy as effective as cisplatin-based chemotherapy in the treatment of advanced-stage dysgerminoma in children, adolescents and young adults? Gynecol Oncol 150, 253-260. Pubmed: 29884437
Poynter, J.N., Richardson, M., Roesler, M., Krailo, M., Amatruda, J.F., and Frazier, A.L. (2018). Family history of cancer in children and adolescents with germ cell tumours: a report from the Children's Oncology Group. Br J Cancer 118, 121-126. Pubmed: 29065103
Pierce, J.L., Frazier, A.L., and Amatruda, J.F. (2018). Pediatric Germ Cell Tumors: A Developmental Perspective. Adv Urol 2018, 9059382. Pubmed: 29515628
Kendall, G.C., Watson, S., Xu, L., LaVigne, C.A., Murchison, W., Rakheja, D., Skapek, S.X., Tirode, F., Delattre, O., and Amatruda, J.F. (2018). PAX3-FOXO1 transgenic zebrafish models identify HES3 as a mediator of rhabdomyosarcoma tumorigenesis. Elife 7. Pubmed: 29869612
Frazier, A.L., Stoneham, S., Rodriguez-Galindo, C., Dang, H., Xia, C., Olson, T.A., Murray, M.J., Amatruda, J.F., Shaikh, F., Pashankar, F., et al. (2018). Comparison of carboplatin versus cisplatin in the treatment of paediatric extracranial malignant germ cell tumours: A report of the Malignant Germ Cell International Consortium. Eur J Cancer 98, 30-37. Pubmed: 29859339
Dicken, B.J., Billmire, D.F., Krailo, M., Xia, C., Shaikh, F., Cullen, J.W., Olson, T.A., Pashankar, F., Malogolowkin, M.H., Amatruda, J.F., et al. (2018). Gonadal dysgenesis is associated with worse outcomes in patients with ovarian nondysgerminomatous tumors: A report of the Children's Oncology Group AGCT 0132 study. Pediatr Blood Cancer 65. Pubmed: 29286555
Chen, K.S., Stroup, E.K., Budhipramono, A., Rakheja, D., Nichols-Vinueza, D., Xu, L., Stuart, S.H., Shukla, A.A., Fraire, C., Mendell, J.T., et al. (2018a). Mutations in microRNA processing genes in Wilms tumors derepress the IGF2 regulator PLAG1. Genes Dev 32, 996-1007. Pubmed: 30026293
Chen, K.S., Fustino, N.J., Shukla, A.A., Stroup, E.K., Budhipramono, A., Ateek, C., Stuart, S.H., Yamaguchi, K., Kapur, P., Frazier, A.L., et al. (2018b). EGF Receptor and mTORC1 Are Novel Therapeutic Targets in Nonseminomatous Germ Cell Tumors. Mol Cancer Ther 17, 1079-1089. Pubmed: 29483210
Woldu, S.L., Amatruda, J.F., and Bagrodia, A. (2017). Testicular germ cell tumor genomics. Curr Opin Urol 27, 41-47. Pubmed: 27584029
Tiwari, B., Kurtz, P., Jones, A.E., Wylie, A., Amatruda, J.F., Boggupalli, D.P., Gonsalvez, G.B., and Abrams, J.M. (2017). Retrotransposons Mimic Germ Plasm Determinants to Promote Transgenerational Inheritance. Curr Biol 27, 3010-3016 e3013. Pubmed: 28966088
Shaikh, F., Cullen, J.W., Olson, T.A., Pashankar, F., Malogolowkin, M.H., Amatruda, J.F., Villaluna, D., Krailo, M., Billmire, D.F., Rescorla, F.J., et al. (2017). Reduced and Compressed Cisplatin-Based Chemotherapy in Children and Adolescents With Intermediate-Risk Extracranial Malignant Germ Cell Tumors: A Report From the Children's Oncology Group. J Clin Oncol 35, 1203-1210. Pubmed: 28240974
Rakheja, D., Chen, K.S., Liu, Y., Shukla, A.A., Schmid, V., Chang, T.C., Khokhar, S., Wickiser, J.E., Karandikar, N.J., Malter, J.S., et al. (2017). Erratum: Publisher Correction: Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours. Nat Commun 8, 16177. Pubmed: 31305780
Moon, J., Zhou, H., Zhang, L.S., Tan, W., Liu, Y., Zhang, S., Morlock, L.K., Bao, X., Palecek, S.P., Feng, J.Q., et al. (2017). Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist. Proc Natl Acad Sci U S A 114, 1649-1654. Pubmed: 28143939
Marcotte, E.L., Pankratz, N., Amatruda, J.F., Frazier, A.L., Krailo, M., Davies, S., Starr, J.R., Lau, C.C., Roesler, M., Langer, E., et al. (2017). Variants in BAK1, SPRY4, and GAB2 are associated with pediatric germ cell tumors: A report from the children's oncology group. Genes Chromosomes Cancer 56, 548-558. Pubmed: 28295819
Lu, Z., Xie, J., Wu, G., Shen, J., Collins, R., Chen, W., Kang, X., Luo, M., Zou, Y., Huang, L.J., et al. (2017). Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation. Nat Med 23, 79-90. Pubmed: 27941793
Liao, Z., Rodrigues, M.C., Poynter, J.N., Amatruda, J.F., Rodriguez-Galindo, C., and Frazier, A.L. (2017). Risk of second malignant neoplasms in women and girls with germ cell tumors. Ann Oncol 28, 329-332. Pubmed: 27864217
Gardiner, J.D., Abegglen, L.M., Huang, X., Carter, B.E., Schackmann, E.A., Stucki, M., Paxton, C.N., Lor Randall, R., Amatruda, J.F., Putnam, A.R., et al. (2017). C/EBPbeta-1 promotes transformation and chemoresistance in Ewing sarcoma cells. Oncotarget 8, 26013-26026. Pubmed: 28148901
Wylie, A., Jones, A.E., D'Brot, A., Lu, W.J., Kurtz, P., Moran, J.V., Rakheja, D., Chen, K.S., Hammer, R.E., Comerford, S.A., et al. (2016). p53 genes function to restrain mobile elements. Genes Dev 30, 64-77. Pubmed: 26701264
Shaikh, F., Murray, M.J., Amatruda, J.F., Coleman, N., Nicholson, J.C., Hale, J.P., Pashankar, F., Stoneham, S.J., Poynter, J.N., Olson, T.A., et al. (2016). Paediatric extracranial germ-cell tumours. Lancet Oncol 17, e149-e162. Pubmed: 27300675
Sanchez, A., and Amatruda, J.F. (2016). Zebrafish Germ Cell Tumors. Adv Exp Med Biol 916, 479-494. Pubmed: 27165367
Pashankar, F., Hale, J.P., Dang, H., Krailo, M., Brady, W.E., Rodriguez-Galindo, C., Nicholson, J.C., Murray, M.J., Bilmire, D.F., Stoneham, S., et al. (2016). Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative. Cancer 122, 230-237. Pubmed: 26485622
Moon, J., and Amatruda, J.F. (2016). Biochemical Analysis of Tankyrase Activity in Zebrafish In Vitro and In Vivo. Methods Mol Biol 1481, 95-100. Pubmed: 27590155
Liao, Z.W., Rodrigues, M.C., Poynter, J.N., Amatruda, J.F., Rodriguez-Galindo, C., and Frazier, A.L. (2016). Risk of second gonadal cancers in women and children with germ cell tumors. Cancer 122, 2076-2082. Pubmed: 27152727
Lee, E., Wei, Y., Zou, Z., Tucker, K., Rakheja, D., Levine, B., and Amatruda, J.F. (2016). Genetic inhibition of autophagy promotes p53 loss-of-heterozygosity and tumorigenesis. Oncotarget 7, 67919-67933. Pubmed: 27655644
Kendall, G.C., and Amatruda, J.F. (2016). Zebrafish as a Model for the Study of Solid Malignancies. Methods Mol Biol 1451, 121-142. Pubmed: 27464805
Dranow, D.B., Hu, K., Bird, A.M., Lawry, S.T., Adams, M.T., Sanchez, A., Amatruda, J.F., and Draper, B.W. (2016). Bmp15 Is an Oocyte-Produced Signal Required for Maintenance of the Adult Female Sexual Phenotype in Zebrafish. PLoS Genet 12, e1006323. Pubmed: 27642754
Roy, A., Kumar, V., Zorman, B., Fang, E., Haines, K.M., Doddapaneni, H., Hampton, O.A., White, S., Bavle, A.A., Patel, N.R., et al. (2015). Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun 6, 8891. Pubmed: 26573325
Rescorla, F.J., Ross, J.H., Billmire, D.F., Dicken, B.J., Villaluna, D., Davis, M.M., Krailo, M., Cullen, J.W., Olson, T.A., Egler, R.A., et al. (2015). Surveillance after initial surgery for Stage I pediatric and adolescent boys with malignant testicular germ cell tumors: Report from the Children's Oncology Group. J Pediatr Surg 50, 1000-1003. Pubmed: 25812445
Olson, T.A., Murray, M.J., Rodriguez-Galindo, C., Nicholson, J.C., Billmire, D.F., Krailo, M.D., Dang, H.M., Amatruda, J.F., Thornton, C.M., Arul, G.S., et al. (2015). Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to Collaboration. J Clin Oncol 33, 3018-3028. Pubmed: 26304902
Frazier, A.L., Hale, J.P., Rodriguez-Galindo, C., Dang, H., Olson, T., Murray, M.J., Amatruda, J.F., Thornton, C., Arul, G.S., Billmire, D., et al. (2015). Revised risk classification for pediatric extracranial germ cell tumors based on 25 years of clinical trial data from the United Kingdom and United States. J Clin Oncol 33, 195-201. Pubmed: 25452439
Stoneham, S.J., Hale, J.P., Rodriguez-Galindo, C., Dang, H., Olson, T., Murray, M., Amatruda, J.F., Thornton, C., Arul, G.S., Billmire, D., et al. (2014). Adolescents and young adults with a "rare" cancer: getting past semantics to optimal care for patients with germ cell tumors. Oncologist 19, 689-692. Pubmed: 24899644
Rakheja, D., Chen, K.S., Liu, Y., Shukla, A.A., Schmid, V., Chang, T.C., Khokhar, S., Wickiser, J.E., Karandikar, N.J., Malter, J.S., et al. (2014). Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours. Nat Commun 2, 4802. Pubmed: 25190313
Puente, B.N., Kimura, W., Muralidhar, S.A., Moon, J., Amatruda, J.F., Phelps, K.L., Grinsfelder, D., Rothermel, B.A., Chen, R., Garcia, J.A., et al. (2014). The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell 157, 565-579. Pubmed: 24766806
Patton, E.E., Dhillon, P., Amatruda, J.F., and Ramakrishnan, L. (2014). Spotlight on zebrafish: translational impact. Dis Model Mech 7, 731-733. Pubmed: 24973741
Lee, E., Koo, Y., Ng, A., Wei, Y., Luby-Phelps, K., Juraszek, A., Xavier, R.J., Cleaver, O., Levine, B., and Amatruda, J.F. (2014). Autophagy is essential for cardiac morphogenesis during vertebrate development. Autophagy 10, 572-587. Pubmed: 24441423
Aloisio, G.M., Nakada, Y., Saatcioglu, H.D., Pena, C.G., Baker, M.D., Tarnawa, E.D., Mukherjee, J., Manjunath, H., Bugde, A., Sengupta, A.L., et al. (2014). PAX7 expression defines germline stem cells in the adult testis. J Clin Invest 124, 3929-3944. Pubmed: 25133429
Wang, X., Moon, J., Dodge, M.E., Pan, X., Zhang, L., Hanson, J.M., Tuladhar, R., Ma, Z., Shi, H., Williams, N.S., et al. (2013). The development of highly potent inhibitors for porcupine. J Med Chem 56, 2700-2704. Pubmed: 23477365
Chen, K.S., and Amatruda, J.F. (2013). A big catch for germ cell tumour research. PLoS Genet 9, e1003481. Pubmed: 23593043
Amatruda, J.F., Ross, J.A., Christensen, B., Fustino, N.J., Chen, K.S., Hooten, A.J., Nelson, H., Kuriger, J.K., Rakheja, D., Frazier, A.L., et al. (2013). DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors. BMC Cancer 13, 313. Pubmed: 23806198
Verduzco, D., Dovey, J.S., Shukla, A.A., Kodym, E., Skaug, B.A., and Amatruda, J.F. (2012). Multiple isoforms of CDC25 oppose ATM activity to maintain cell proliferation during vertebrate development. Mol Cancer Res 10, 1451-1461. Pubmed: 22986406
Moro, E., Ozhan-Kizil, G., Mongera, A., Beis, D., Wierzbicki, C., Young, R.M., Bournele, D., Domenichini, A., Valdivia, L.E., Lum, L., et al. (2012). In vivo Wnt signaling tracing through a transgenic biosensor fish reveals novel activity domains. Dev Biol 366, 327-340. Pubmed: 22546689
Leacock, S.W., Basse, A.N., Chandler, G.L., Kirk, A.M., Rakheja, D., and Amatruda, J.F. (2012). A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis. Dis Model Mech 5, 95-106. Pubmed: 21979944
Huang, G.N., Thatcher, J.E., McAnally, J., Kong, Y., Qi, X., Tan, W., DiMaio, J.M., Amatruda, J.F., Gerard, R.D., Hill, J.A., et al. (2012). C/EBP transcription factors mediate epicardial activation during heart development and injury. Science 338, 1599-1603. Pubmed: 23160954
Hajeri, V.A., and Amatruda, J.F. (2012). Studying synthetic lethal interactions in the zebrafish system: insight into disease genes and mechanisms. Dis Model Mech 5, 33-37. Pubmed: 22107871
Dodge, M.E., Moon, J., Tuladhar, R., Lu, J., Jacob, L.S., Zhang, L.S., Shi, H., Wang, X., Moro, E., Mongera, A., et al. (2012). Diverse chemical scaffolds support direct inhibition of the membrane-bound O-acyltransferase porcupine. J Biol Chem 287, 23246-23254. Pubmed: 22593577
Verduzco, D., and Amatruda, J.F. (2011). Analysis of cell proliferation, senescence, and cell death in zebrafish embryos. Methods Cell Biol 101, 19-38. Pubmed: 21550438
Paulson, V., Chandler, G., Rakheja, D., Galindo, R.L., Wilson, K., Amatruda, J.F., and Cameron, S. (2011). High-resolution array CGH identifies common mechanisms that drive embryonal rhabdomyosarcoma pathogenesis. Genes Chromosomes Cancer 50, 397-408. Pubmed: 21412928
Neumann, J.C., Lillard, K., Damoulis, V., and Amatruda, J.F. (2011a). Zebrafish models of germ cell tumor. Methods Cell Biol 105, 3-24. Pubmed: 21951524
Neumann, J.C., Chandler, G.L., Damoulis, V.A., Fustino, N.J., Lillard, K., Looijenga, L., Margraf, L., Rakheja, D., and Amatruda, J.F. (2011b). Mutation in the type IB bone morphogenetic protein receptor Alk6b impairs germ-cell differentiation and causes germ-cell tumors in zebrafish. Proc Natl Acad Sci U S A 108, 13153-13158. Pubmed: 21775673
Jacob, L.S., Wu, X., Dodge, M.E., Fan, C.W., Kulak, O., Chen, B., Tang, W., Wang, B., Amatruda, J.F., and Lum, L. (2011). Genome-wide RNAi screen reveals disease-associated genes that are common to Hedgehog and Wnt signaling. Sci Signal 4, ra4. Pubmed: 21266715
Fustino, N., Rakheja, D., Ateek, C.S., Neumann, J.C., and Amatruda, J.F. (2011). Bone morphogenetic protein signalling activity distinguishes histological subsets of paediatric germ cell tumours. Int J Androl 34, e218-233. Pubmed: 21696393
Poynter, J.N., Amatruda, J.F., and Ross, J.A. (2010). Trends in incidence and survival of pediatric and adolescent patients with germ cell tumors in the United States, 1975 to 2006. Cancer 116, 4882-4891. Pubmed: 20597129
Pon, L., and Amatruda, J.F. (2010). Breast cancer between faith and medicine: the Peres Maldonado ex-voto. Med Humanit 36, 112-114. Pubmed: 21393294
Research
Pediatric sarcomas driven by fusion oncogenes
Germ cell tumors of the ovary and testis
DICER1-related cancers including Wilms tumor of the kidney
Visit the Amatruda Laboratory.
