About the Lab
Due to the relatively inferior long-term patient outcomes, we recognize the need for improving our understanding of pediatric sarcomas, specifically osteosarcoma, Ewing sarcoma and rhabdomyosarcoma. The laboratory has tremendous interest and experience in merging innovative murine models and patient-derived resources towards garnering molecular insights into sarcoma initiation, development and metastatic progression and translating these findings towards testing novel therapeutic interventions.
Research in our laboratory is focused on these areas:
- Utilizing tissue-specific genetic perturbation to form novel, applicable transgenic mouse models of metastatic osteosarcoma and rhabdomyosarcoma, both conditions that have particularly poor patient outcomes. Such models allow for further understanding of critical genetic and proteomic alterations involved in sarcoma development, progression and metastasis and can be utilized as preclinical models for therapeutic testing and efficacy.
- Use of innovative in vitro, ex vivo and in vivo models in order to investigate the roles of critical signal transduction mechanisms, such as the Wnt-signaling pathway, in the metastatic and therapeutic resistant conditions.
- Investigating the role and the therapeutic potential of the tumor microenvironment, focusing on non-tumor cell contributions and metabolic alterations, towards sarcoma initiation, development and progression.
We have developed multiple collaborations within ÌÇÐÄÊÓƵ of Medicine, as well as local, domestic and international institutions to further enhance our studies from a basic science and translational/clinical approach. Also, utilizing the strengths and resources of the Developmental Therapeutics Program at Texas Children’s Cancer Center, we have formed collaborations with multiple pharmaceutical companies to test the efficacy of novel therapeutic agents on pediatric sarcomas.
Yunstein Lab in the News
Nomura M, Rainusso N, Lee Y, Dawson B, Coarfa C, Han R, Larson J, Shuck R, Kurenbekova L, Yustein, JT. 2019. Tegavivint and the β-catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma. Journal of the National Cancer Institute. 111(11):1216-1227. doi: 10.1093/jnci/djz026.
Tsang S, Patel T, Yustein JT. 2019. Long Non-Coding RNAs Regulation of Therapeutic Resistance. Cancer Drug Resistance. 2:550-567, 10.20517/cdr.2019.58.
Bailey K, Cost C, Davis I, Glade-Bender J, Grohar P, Houghton P, Isakoff M, Stewart E, Laack N, Yustein JT, Reed D, Janeway K, Gorlick R, Lessnick S, DuBois S, Hingorani P. 2019. Emerging Novel Agents for Patients with Advanced Ewing Sarcoma: A Report From The Children’s Oncology Group (COG) New Agents for Ewing Sarcoma Task Force. Faculty of 1000., 8: F1000 Faculty Rev-493, doi: 10.12688/f1000research.18139.1.
Rainusso N, Cleveland H, Hernandez J, Quintanilla N, Hicks J, Vasudevan S, Marco R, Allen-Rhoades W, Wang L, and Yustein JT. 2018. Generation of Patient-Derived Tumor Xenografts from Percutaneous Tumor Biopsies in Children with Bone Sarcomas. Pediatric Blood Cancer. e27579. doi: 10.1002/pbc.27579.
Fuja D, Rainusso N, Shuck R, Kurenbekova L, Donehower L, Yustein JT. 2018. Transglutaminase-2 Promotes Metastatic and Stem-Like Phenotypes in Osteosarcoma. American Journal of Cancer Research. 8(9):1752-1763.
Shapiro M, Tang T, Dasgupta A, Kurenbekova L, Shuck R, Gaber M., and Yustein JT. 2018. In vitro and in vivo characterization of a preclinical radiation-adapted model for Ewing sarcoma. International Journal of Radiation Oncology, Biology, Physics. 101(1):118-127. doi: 10.1016/j.ijrobp.2018.01.095.
Dasgupta A, Trucco M, Rainusso N, Bernardi R, Shuck R, Kurenbekova L, Loeb D, Yustein JT. 2017. Metabolic Modulation of Ewing Sarcoma Cells Inhibits Tumor Growth and Stem Cell Properties. Oncotarget. 8(44):77292-77308. doi: 10.18632/oncotarget.20467.
Satterfield L, Shuck R, Kurenbekova L, Allen-Rhoades W, Edwards D, Huang S, Rajapakshe K, Coarfa C, Donehower L, Yustein JT. 2017. miR-130b directly targets ARHGAP1 to drive activation of a metastatic CDC42-PAK1-AP1 positive feedback loop in Ewing sarcoma. International Journal of Cancer. 141(10):2062-2075. doi: 10.1002/ijc.30909.
Dasgupta A, Nomura M, Shuck R, Yustein JT. 2017. Cancer's Achilles' Heel: Apoptosis and Necroptosis to the Rescue. International Journal of Molecular Sciences. 18(1): 23.
Techavichit P, Gao Y, Kurenbekova L, Shuck R, Donehower L, and Yustein JT. 2016. Secreted Frizzled-Related Protein 2 (sFRP2) promotes osteosarcoma invasive and metastatic potential. BMC Cancer. 16(1):869. doi: 10.1186/s12885-016-2909-6.
Yang X, Chaudhury A, Zhang M, Savoldo B, Metelitsa L, Rodgers J, Yustein JT, Neilson J, Dotti G. 2016. T effector-memory cells are adapted to hypoxia through HIF1α and glycolytic metabolism. Journal of Clinical Investigation. 126(7):2678-88. doi: 10.1172/JCI85834.
Rao P, Zhao S, Zhao Y, Yu A, Rainusso N, Trucco M, Allen-Rhoades W, Satterfield L, Fuja D, Borra V, Man T, Donehower L, Yustein JT. 2015. Co-Amplification of Myc/Pvt1 and Homozygous Deletion of Nlrp1 Locus are the Frequent Genetics Changes in Mouse Osteosarcoma. Genes, Chromosomes and Cancer. doi: 10.1002/gcc.22291.
Roos A, Satterfield L, Zhao S, Fuja D, Shuck R, Hicks J, Donehower L, and Yustein JT. 2015. Loss of Runx2 sensitises osteosarcoma to chemotherapy-induced apoptosis. British Journal of Cancer. 113(9):1289-97. doi: 10.1038/bjc.2015.305.
Allen-Rhoades W, Kurenbekova L, Satterfield L, Parikh N, Fuja D, Shuck R, Rainusso N, Trucco M, Barkauskas D, Jo E, Ahern C, Hilsenbeck S, Donehower L, Yustein JT. 2015. Cross-Species Identification of a Plasma MicroRNA Signature for Detection, Therapeutic Monitoring, and Prognosis in Osteosarcoma. Cancer Medicine. 4(7):977-88.
Zhao S, Kurenbekova L, Gao Y, Roos A, Creighton C, Rao P, Hicks J, Man T, Lau C, Brown A, Jones S, Lazar A, Ingram D, Lev D, Donehower L, Yustein JT. 2015. NKD2, a Negative Regulator of Wnt Signaling, Suppresses Tumor Growth and Metastasis in Osteosarcoma. Oncogene. doi:10.1038/onc.2014.429
Ribbon Cutting for Faris D. Virani Ewing Sarcoma Center at Texas Children's Cancer Center
Ewing sarcoma is the second most common bone tumor in children. As one of the most challenging forms of cancer to treat, these tumors often originate in large bones such as the hip, shin, chest and arm bones. Approximately 250 new cases of this type of tumor are diagnosed in the United States per year.
CureSearch Young Investigator - Jason Yustein, M.D., Ph.D.
CureSearch Young Investigator Jason Yustein, M.D., Ph.D., talks about his research project "Novel Mouse Models of Metastatic Rhabdomyosarcoma."