Myron Ignatius, PhD

  • Rank: Assistant Professor
  • Department: Molecular Medicine
  • Office: 3.100.12
  • Location: Greehey CCCRI
  • Tel: 1.210.562.9030

 

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.

 

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.

 

Figure 3: Transgenic strategy in zebrafish to label cancer-stem cell and other tumor populations in vivo in zebrafish (left). Example of a limit dilution cell transplantation experiment, using the approach in the left panel, Cancer Stem Cell /Tumor-propagating cell number can be calculated by transplanting tumor cells at different dilutions into syngeneic matched recipients (Ignatius et al., Cancer Cell 2012). Only a Tumor-propagating cell/ Cancer Stem Cell will generate a new tumor.

 

Figure 4: Example of an in vivo drug screen performed in zebrafish, screening 110 compounds and using 2200 zebrafish (Chen E., DeRan M., Ignatius M et al., PNAS 2014)

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

 

 

Federal


Funding Agency K99/R00 National Institutes of Health (NCI)
Title A role for Notch in self-renewal in Embryonal Rhabdomyosarcoma.
Status Active Active
Period 2014-2019
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.

State

Funding Agency CPRIT- First Time Tenure Track Award
Title Understanding Functional Heterogeneity in Sarcomas
Status Active Active
Period 2016
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
Period 2016
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