Dr. Myron Ignatius's lab seeks to discover novel treatments in relapsed pediatric cancer by defining tumor heterogeneity and its effects 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 how subsets of tumor cells self-renew, metastasize and evolve at relapse using a combination of zebrafish, murine xenograft and human cell culture systems.
Figure 1: Research using a Zebrafish tumor model of Embryonal Rhabdomyosarcoma employs a combination of approaches and assays including Bioinformatic, High-throughput cell transplantation, Chemical-Genetic Screens and In vivo imaging.
Figure 2: ERMS tumors are generated in vivo using the human kRASG12D oncogene. RAS is the major driver of this disease in children with ERMS. Tumors arise as quickly as 10 days after transgene expression.
Ignatius, M. S., Moose, H. E., El - Hodiri, H. M. and Henion, P. D. (2008). Colgate/hdac1 repression of foxd3 expression is required to permit mitfa-dependent melanogenesis, Dev. Biol.313(2), 568-83.
Ignatius, M. S. and Langenau, D. M. (2009). Zebrafish as a Model for Cancer Self-renewal. Zebrafish. Dec;6(4):377-87. Author, Review.
Ignatius M.S., Chen E., Elpek N.M., Fuller A., Tenente I.M., Clagg R., Liu S., Blackburn J.S., Linardic C., Rosenberg A., Neilsen P.G., Mempel T.R., Langenau D.M. (2012). In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma. Cancer Cell. 2012; 21(5):680-93.
Chen E.Y., DeRan M., Ignatius M.S., Grandinetti K.B., Ryan Clagg, McCarthy K, Lobbardi R.M., Brockmann J., Keller C., Wu X., Langenau D.M. (2014). GSK3 inhibitors induce the canonical WNT/-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma. PNAS. 2014; 111(14):55349-54. 10.
Tang Q., Moore J.C., Ignatius M.S., Hayes M.N., Tenente I, Bourque C., He S., Look A.T., Garcia E.C., Blackburn J.S., Houvras Y., Langenau D.M. (2016). Imaging the dynamics of tumour cell heterogeneity following cell transplantation into optically-clear rag2E450fs zebrafish. Nature Communications. 2016 Jan 21; 7:10358.
Link to lab page.