We are interested in better understanding how dysregulated oncogenic signaling networks interact to drive aggressive phenotypes, such as self-renewal, chemoresistance, and metastasis in pediatric solid tumors. Our major focus centers on high-risk neuroblastoma, a tumor of the developing nervous system that continues to account for a significant portion of deaths in pediatric oncology. We recently showed that LIN28B, an RNA binding protein that sustains normal stem cell physiology, coordinates a novel oncogenic signaling network in neuroblastoma (Schnepp, et al. Cancer Cell 2015). One major focus of the laboratory is dedicated to investigating the hallmarks of cancer that this oncogenic driver controls and determining the mechanisms it employs to do so. By thoroughly characterizing this network, we aim to define novel therapeutic targets in neuroblastoma and potentially reveal new opportunities for intervention. A second focus, which emerges naturally from our studies on LIN28B, implicated in metastasis in several histotypes of cancer, centers around determining the mechanisms that neuroblastoma cells use to disseminate and metastasize. In this arena, we are pursuing specific hypotheses as well as nominating novel genes and pathways of interest utilizing a variety of high-throughput approaches. Finally, as the laboratory matures, we have plans to broaden our studies to another childhood tumor, rhabdomyosarcoma, which, especially in the metastatic context, is extraordinarily challenging to cure.  Overall, our goal is to leverage the findings generated from our studies to improve therapeutic options for people diagnosed with these malignancies.   

  • Schnepp RW, Diskin S. LIN28B: An Orchestrator of Oncogenic Signaling in Neuroblastoma. Cell Cycle. Published online January 8, 2016.  

  • Schnepp RW, Khurana P, Attiyeh EF, Raman P, Chodosh SE, Oldridge DA, Gagliardi ME, Conkwrite K, Asgharzadeh S, Seeger RC, Madison BB, Rustgi AK, Maris JM, Diskin SD. A LIN28B-RAN-AURKA Signaling Network promotes Neuroblastoma Tumorigenesis. Cancer Cell. 2015 Nov 9;28(5):599-609, (PMID: 26481147); (PMCID: PMC4643330).

  • Schnepp RW, Bosse KR, and Maris JM. Improving Patient Outcomes With Cancer Genomics: Unique Opportunities and Challenges in Pediatric Oncology. JAMA.  2015 Sep 1; 314(9):881-3. (PMID: 26325556); (PMCID: PMC4599710).  

  • Rader J, Russell MR, Hart LS, Nakazawa MS, Belcastro LT, Martinez D, Li Y, Carpenter EL, Attiyeh EF, Diskin SJ, Kim S, Parasuraman S, Caponigro G, Schnepp RW, Wood AC, Pawel B, Cole KA and Maris JM.  Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma.  Clinical Cancer Research.  2013 Nov 15; 19(22):6173-82, (PMID: 24045179); (PMCID: PMC3844928).

  • Diskin SJ, Capasso M, Schnepp RW, Cole KA, Attiyeh EA, Hou C, Diamond M, Carpenter EL, Winter C, Lee H, Jagannathan J, Latorre V, Iolascon A, Hakanarson H, Devoto M and Maris JM. Identification of two new neuroblastoma susceptibility loci at 6q16 within HACE1 and LIN28B. Nature Genetics. 2012 Oct; 44(10):1126-30.  Epub 2012 Sep 2, (PMID: 22941191).  

  • Diskin SJ, Capasso M, Schnepp RW, Cole KA, Attiyeh EA, Hou C, Diamond M, Carpenter EL, Winter C, Lee H, Jagannathan J, Latorre V, Iolascon A, Hakanarson H, Devoto M and Maris JM. Identification of two new neuroblastoma susceptibility loci at 6q16 within HACE1 and LIN28B. Nature Genetics. 2012 Oct; 44(10):1126-30.  Epub 2012 Sep 2, (PMID: 22941191).  

  • Schnepp RW, Chen Y-X, Wang H, Cash T, Silva AJ, Diehl JA, Brown EJ, and Hua X.  Mutation of Tumor Suppressor Men1 Acutely Enhances Proliferation of Pancreatic Islet Cells.  Cancer Research.  2006 Jun 1;66(11):5707-15,  (PMID: 16740708); (PMCID: PMC2839933).

  • Schnepp RW, Hou Z, Wang H, Petersen C, Silva A, Masai H, Hua X.  Functional interaction between tumor suppressor menin and activator of S-phase kinase (ASK). Cancer Res. 2004 Sep 15; 64(18):6791-6, (PMID: 15374998). 

  • Schnepp RW, Mao H, Sykes SM, Zong WX, Silva A, La P, Hua X. Menin induces apoptosis in murine embryonic fibroblasts. J Biol Chem. 2004 Mar 12;279(11):10685-91,  (PMID: 14688275).