Discover novel treatments in relapsed pediatric cancer by defining tumor heterogeneity and its effect on self-renewal and metastasis.
The Ignatius laboratory is interested in understanding the effects of tumor heterogeneity on relapse and resistance to therapies in Rhabdomyosarcoma and other sarcomas. Relapse is a major problem in the clinic where less that 40% of patients with relapse will survive their disease. Rhabdomyosarcoma is a pediatric malignancy of the muscle that is also the most common soft tissue sarcoma in children. Specifically, the Ignatius laboratory will study tumorigenic cell populations that self-renew and metastasize using a combination of zebrafish, murine xenograft and human cell culture systems.
In addition to research on rhabdomyosarcoma, the Ignatius laboratory has also generated new syngeneic zebrafish models of aggressive Malignant Nerve Sheath Tumors and hemangiosarcomas for which there are no effective treatments. Our research will uncover important molecular pathways that modulate Tumor propagating cell number and the plasticity of the cancer stem cell state. A unique and innovative aspect of our research is the ability to visualize in live animals the evolution of tumors and to model the effects of patient specific changes on tumor dynamics. Research in the laboratory will combine sequencing platforms with zebrafish tumor models to identify new genes or pathways that drive relapse with the goal of identifying nodes to target with personalized medicines in children with relapsed cancer.
Myron Ignatius, Ph.D., joined Greehey Children’s Cancer Research Institute as a Principal Investigator in the Fall of 2016 with major responsibilities in Molecular Oncogenesis and Cancer Genetics. Dr. Ignatius also holds the position of Assistant Professor in the Department of Molecular Medicine at the University of Texas Health Sciences Center in San Antonio. His area of interest is exploring the effects of tumor heterogeneity on relapse and resistance to therapies in sarcomas. Relapse is a major clinical challenge with children with pediatric cancer including sarcomas. Dr. Ignatius received his doctoral degree from The Ohio State University and he did his Post-doctoral training at Harvard Medical School and Massachusetts General Hospital.
Zebrafish Cancer Models and genetics
Embryonal Rhabdomyosarcoma research
Stem Cell Biology
Funding Agency K99/R00 National Institutes of Health (NCI)
Title A role for Notch in self-renewal in Embryonal Rhabdomyosarcoma.
Status Active Active
Role Principal Investigator
Grant Detail The major goal of this project is to determine the effects of misregulation of Notch signaling pathway on relapse or tumor propagating cell self-renewal in Embryonal Rhabdomyosarcoma. Building on earlier experiments, this proposal will identify Notch regulated targets that drive tumor relapse and differentiation. Understanding Notch signaling effects in this pediatric solid tumor can potentially lead to new avenues of treatment.
Funding Agency CPRIT- First Time Tenure Track Award
Title Understanding Functional Heterogeneity in Sarcomas
Status Active Active
Role Principal Investigator
Grant Detail Relapse is the major problem in the clinic and understanding how tumors change or evolve at relapse is the focus of this grant. We will use the power of modeling tumors in zebrafish in combination with patient derived cell lines and tumors and murine xenograft models to define tumor heterogeneity. Zebrafish tumor models provide a unique discovery platform for in vivo drug screens, imaging and genetics. From these studies we hope to identify new pathways to target in rhabdomyosarcoma and new sarcoma models we have generated and our currently characterizing.
Funding Agency UT Rising STARs Award
Status Active Active
Role Principal Investigator
|Year||Name of Honor/Prize||Awarding Organization|
|2016||CPRIT Scholar||Cancer Prevention & Research Institute of Texas|
|2014||Researcher of the Month, Alex’s Lemonade Stand Foundation||Alex’s Lemonade Stand Foundation, a pediatric cancer foundation|
|2014||K99R00 Career Development Award||NCI (NIH)|
|2013||Alex’s Lemonade Stand ‘A’ award||Alex’s Lemonade Stand Foundation, a pediatric cancer foundation|
|2012||Executive Committee On Research (ECOR) Fund for Medical Discovery Postdoctoral award||Massachusetts General Hospital|
|2010||Travel Award||International Society for Stem Cell Research Conference Massachusetts General Hospital|
|2009||Poster competition - 1st Place||Cancer Center Retreat|
|2000||Council for Scientific and Industrial Research Junior Research Fellowship||Council for Scientific and Industrial Research – Competitive fellowship granted by the Indian government|
The NOTCH1/SNAIL1/MEF2C Pathway Regulates Growth and Self-Renewal in Embryonal Rhabdomyosarcoma. Ignatius MS, Hayes MN, Lobbardi R, Chen EY, McCarthy KM, Sreenivas P, Motala Z, Durbin AD, Molodtsov A, Reeder S, Jin A, Sindiri S, Beleyea BC, Bhere D, Alexander MS, Shah K, Keller C, Linardic CM, Nielsen PG, Malkin D, Khan J, Langenau DM. Cell Rep. 2017 Jun 13;19(11):2304-2318. doi: 10.1016/j.celrep.2017.05.061. PMID: 28614716
Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. Tenente IM, Hayes MN, Ignatius MS, McCarthy K, Yohe M, Sindiri S, Gryder B, Oliveira ML, Ramakrishnan A, Tang Q, Chen EY, Petur Nielsen G, Khan J, Langenau DM. Elife. 2017 Jan 12;6. pii: e19214. doi: 10.7554/eLife.19214. PMID: 28080960
In Vivo Imaging of Cancer in Zebrafish. Ignatius MS, Hayes M, Langenau DM. Adv Exp Med Biol. 2016;916:219-37. doi: 10.1007/978-3-319-30654-4_10. Review. PMID: 27165356
Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish. Tang Q, Moore JC, Ignatius MS, Tenente IM, Hayes MN, Garcia EG, Torres Yordán N, Bourque C, He S, Blackburn JS, Look AT, Houvras Y, Langenau DM. Nat Commun. 2016 Jan 21;7:10358. doi: 10.1038/ncomms10358. PMID: 26790525
Optimized cell transplantation using adult rag2 mutant zebrafish. Tang Q, Abdelfattah NS, Blackburn JS, Moore JC, Martinez SA, Moore FE, Lobbardi R, Tenente IM, Ignatius MS, Berman JN, Liwski RS, Houvras Y, Langenau DM. Nat Methods. 2014 Aug;11(8):821-4. doi: 10.1038/nmeth.3031. Epub 2014 Jul 20. PMID: 25042784
Glycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma. Chen EY, DeRan MT, Ignatius MS, Grandinetti KB, Clagg R, McCarthy KM, Lobbardi RM, Brockmann J, Keller C, Wu X, Langenau DM. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5349-54. doi: 10.1073/pnas.1317731111. Epub 2014 Mar 24. PMID: 24706870
Cross-species array comparative genomic hybridization identifies novel oncogenic events in zebrafish and human embryonal rhabdomyosarcoma. Chen EY, Dobrinski KP, Brown KH, Clagg R, Edelman E, Ignatius MS, Chen JY, Brockmann J, Nielsen GP, Ramaswamy S, Keller C, Lee C, Langenau DM. PLoS Genet. 2013 Aug;9(8):e1003727. doi: 10.1371/journal.pgen.1003727. Epub 2013 Aug 29. PMID: 24009521
Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development. Ignatius MS, Unal Eroglu A, Malireddy S, Gallagher G, Nambiar RM, Henion PD. PLoS One. 2013 May 7;8(5):e63218. doi: 10.1371/journal.pone.0063218. Print 2013. PMID: 23667588
A novel chemical screening strategy in zebrafish identifies common pathways in embryogenesis and rhabdomyosarcoma development. 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. Development. 2013 Jun;140(11):2354-64. doi: 10.1242/dev.088427. Epub 2013 Apr 24. PMID: 23615277
In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma. Ignatius MS, Chen E, Elpek NM, Fuller AZ, Tenente IM, Clagg R, Liu S, Blackburn JS, Linardic CM, Rosenberg AE, Nielsen PG, Mempel TR, Langenau DM. Cancer Cell. 2012 May 15;21(5):680-93. doi: 10.1016/j.ccr.2012.03.043. PMID: 22624717
Fluorescent imaging of cancer in zebrafish. Ignatius MS, Langenau DM. Methods Cell Biol. 2011;105:437-59. doi: 10.1016/B978-0-12-381320-6.00019-9. PMID: 21951542
High-throughput imaging of adult fluorescent zebrafish with an LED fluorescence macroscope. Blackburn JS, Liu S, Raimondi AR,Ignatius MS, Salthouse CD, Langenau DM. Nat Protoc. 2011 Feb;6(2):229-41. doi: 10.1038/nprot.2010.170. Epub 2011 Feb 3. PMID: 21293462
High-throughput cell transplantation establishes that tumor-initiating cells are abundant in zebrafish T-cell acute lymphoblastic leukemia. Smith AC, Raimondi AR, Salthouse CD, Ignatius MS, Blackburn JS, Mizgirev IV, Storer NY, de Jong JL, Chen AT, Zhou Y, Revskoy S, Zon LI, Langenau DM. Blood. 2010 Apr 22;115(16):3296-303. doi: 10.1182/blood-2009-10-246488. Epub 2010 Jan 7. PMID: 20056790
Zebrafish as a model for cancer self-renewal. Ignatius MS, Langenau DM. Zebrafish. 2009 Dec;6(4):377-87. doi: 10.1089/zeb.2009.0610. PMID: 19954344
colgate/hdac1 Repression of foxd3 expression is required to permit mitfa-dependent melanogenesis. Ignatius MS, Moose HE, El-Hodiri HM, Henion PD. Dev Biol. 2008 Jan 15;313(2):568-83. Epub 2007 Nov 9. PMID: 18068699
Zebrafish colgate/hdac1 functions in the non-canonical Wnt pathway during axial extension and in Wnt-independent branchiomotor neuron migration. Nambiar RM, Ignatius MS, Henion PD. Mech Dev. 2007 Sep-Oct;124(9-10):682-98. Epub 2007 Jul 14. PMID: 17716875
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