About the Laboratory
The Pediatric Surgical Oncology Laboratory performs cutting-edge clinical and translational / basic science research focusing on pediatric solid tumors. Led by Sanjeev A. Vasudevan, M.D., the lab's research work is focused on finding new cures through cancer modeling, genetic profiling, and preclinical testing of novel targeted agents.
The PSOL collaborates with the Texas Children’s Cancer Center to translate bench top research into tangible therapeutics for children.
The primary focus of the PSOL is high-risk pediatric liver cancer. Hepatoblastoma and hepatocellular carcinoma are the most prevalent liver cancers seen in children, and the incidences of these malignancies are on the rise worldwide. Our primary projects are as follows:
- Harnessing the p53 tumor suppressor pathway to induce cell death in these tumors
- Profiling and targeting the most aggressive cellular populations within liver cancers, including sub-clones of vascular invasion and circulating tumor cells
- Creating the most robust collection of patient-derived cell lines and xenografts of high-risk liver cancer
- Testing other novel targeted therapies to provide pre-clinical data to support new clinical trials for patients with tumors that do not respond to established therapies
- Developing new intraoperative surgical imaging techniques to improve the outcomes of children undergoing cancer surgery
Using this same approaches, our lab also focuses on neuroblastoma and other rare but deadly pediatric cancers.
Funded Projects
Cancer Prevention and Research Institute of Texas
Predictive biomarkers and novel therapies for high-risk pediatric liver cancers.
Elucidate the mechanisms behind chemoresistance and vascular invasion in high-risk pediatric liver cancer.
- Determine the major regulators of p53 tumor suppressor silencing and methods of reactivating tumor suppressor signaling in high-risk pediatric liver cancer.
- Determine the differential gene expression and pathway regulation within areas of vascular invasion in high-risk HB in order to target susceptible pathways.
- Test the susceptibility and response of patient-derived xenografts from high-risk and relapse/refractory pediatric liver cancer patients to targeted MDM4/p53, JAK/STAT3 agents and GPC3 CAR T-cell immunotherapy.
Cancer Prevention and Research Institute of Texas
Patient-Derived Xenografts and Advanced In Vivo Models (PDX-AIM) Core Facility.
Develop patient-derived xenografts for pediatric and adult liver cancer using novel engrafting methods.
- Improve tumor implantation rate for liver cancer PDX’s.
- Develop tumor spheroid and matrigel-coated plasticware techniques as intermediaries for biopsy samples.
- Use circulating tumor cells to generate PDX models when primary tissue samples are not available.
Macy Easom Cancer Research Foundation Grant
Development of novel targeted therapies for hepatoblastoma using patient-derived xenografts.
- Establish a core panel of patient-derived xenografts and cell lines for high risk and relapsed hepatoblastoma patients.
- Test effects of MDM4 and DUSP9 inhibition on tumorigenesis of hepatoblastoma.
Laboratory Publications
Whitlock RS, Yang T, Vasudevan SA, Woodfield SE. (2020). Animal modeling of pediatric liver cancer. Cancers. Cancers (Basel). 12(2):273.
Jin J, Patel RH, Woodfield SE, Shi Y, Jin NG, Sun W, Yu Y, Vasudevan SA. Targeting LRH-1 in hepatoblastoma cell lines causes decreased proliferation. (2019). Oncology Reports. 41(1):143-153.
Woodfield SE*, Shi Y*, Patel RH, Jin J, Major A, Sarabia SF, Starosolski Z, Zorman B, Gupta SS, Chen Z, Ibarra AM, Bissig KD, Ghaghada KB, Sumazin P, Lopez-Terrada D, Vasudevan SA. A novel cell line based orthotopic xenograft mouse model that recapitulates human hepatoblastoma. Scientific Reports. 2017 Dec 19;7(1):17751. doi: 10.1038/s41598-017-17665-8.
Shi Y*, Commander SJ*, Masand PM, Heczey A, Goss JA, Vasudevan SA.Vascular invasion is a prognostic indicator in hepatoblastoma. J Pediatr Surg. 2017 Mar 16. pii: S0022-3468(17)30166-5. doi: 10.1016/j.jpedsurg.2017.03.017. [Epub ahead of print] PubMed PMID: 28347528.
Shi Y*, Rojas Y*, Zhang W, A Beierle E, J Doski J, Goldfarb M, B Goldin A, W Gow K, Langer M, L Meyers R, G Nuchtern J, Vasudevan SA. Characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver: A report from the National Cancer Database. Pediatr Blood Cancer. 2016 Oct 26. doi: 10.1002/pbc.26272. [Epub ahead of print] PubMed PMID: 27781381.
Parsons DW, Roy A, Yang Y, Wang T, Scollon S, Bergstrom K, Kerstein RA, Gutierrez S, Petersen AK, Bavle A, Lin FY, López-Terrada DH, Monzon FA, Hicks MJ, Eldin KW, Quintanilla NM, Adesina AM, Mohila CA, Whitehead W, Jea A, Vasudevan SA, Nuchtern JG, Ramamurthy U, McGuire AL, Hilsenbeck SG, Reid JG, Muzny DM, Wheeler DA, Berg SL, Chintagumpala MM, Eng CM, Gibbs RA, Plon SE. Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors. JAMA Oncol. 2016 Jan 28. doi: 10.1001/jamaoncol.2015.5699. [Epub ahead of print] PubMed PMID: 26822237.
Bissig-Choisat B, Kettlun-Leyton C, Legras XD, Zorman B, Barzi M, Chen LL, Amin MD, Huang YH, Pautler RG, Hampton OA, Prakash MM, Yang D, Borowiak M, Muzny D, Doddapaneni HV, Hu J, Shi Y*, Gaber MW, Hicks MJ, Thompson PA, Lu Y, Mills GB, Finegold M, Goss JA, Parsons DW, Vasudevan SA, Sumazin P, López-Terrada D, Bissig KD. Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer. J Hepatol. 2016 Aug;65(2):325-33. doi: 10.1016/j.jhep.2016.04.009. PubMed PMID: 27117591.
Ma IT*, Rojas Y*, Masand PM, Castro EC, Himes RW, Kim ES, Goss JA, Nuchtern JG, Finegold MJ, Thompson PA, Vasudevan SA. Focal nodular hyperplasia in children: an institutional experience with review of the literature. J Pediatr Surg. 2015; 50(3):382-7.
Shi Y*, Ma IT*, Patel RH, Shang X, Chen Z, Zhao Y, Cheng J, Fan Y, Rojas Y*, Barbieri E, Chen Z, Yu Y, Jin J, Kim ES, Shohet JM, Yang J, Vasudevan SA. NSC-87877 inhibits DUSP26 function in neuroblastoma resulting in p53-mediated apoptosis. Cell Death Dis. 2015;6:e1841.. PMID: 26247726; PMCID: PMC4558500
Shi Y*, Geller JI, Ma IT*, Chavan RS, Masand PM, Towbin AJ, Chintagumpala M, Nuchtern JG, Tiao GM, Thompson PA, Vasudevan SA. Relapsed hepatoblastoma confined to the lung is effectively treated with pulmonary metastasectomy. J Pediatr Surg. 2015, in press
Felsted AE*, Shi Y*, Masand PM, Nuchtern JG, Goss JA, Vasudevan SA. Intraoperative ultrasound for liver tumor resection in children. J Surg Res. 2015;198(2):418-23. PMID: 25940155