Jason M. Shohet, M.D., Ph.D.
Department of Pediatrics
Section of Hematology-Oncology
Baylor College of Medicine
Chair - Neuroblastoma Program
Texas Children's Cancer Center & Hematology Service
- M.D., Ph.D., Boston University School of Medicine, Boston, MA
- Internship, Residency and Fellowship, Baylor College of Medicine
- Fellowship, The University of Texas Southwestern Medical Center
- American Board of Pediatrics
- American Board of Pediatrics-Hematology/Oncology
Dr. Shohet’s research is focused on developing better molecular targeted therapies for neuroblastoma and other solid tumors. Mortality and morbidity from neuroblastoma is still a major challenge in pediatric oncology and novel improved therapies are urgently needed. Effective biologically specific therapies will derive from a deeper understanding of the molecular processes crucial for tumor transformation and progression. An ideal therapeutic target is essential for tumor development and growth, is amenable to genetic or pharmacologic destruction and can be specifically targeted in malignant cells. Current technologies (e.g. retroviral transfer of RNAi, microRNA and Microarray gene expression profilingorthotopic) coupled with tumor xenografting protocols permit detailed analysis of the genes and proteins essential for malignant transformation and growth. The MYCN oncogene plays a critical role in the development and progression of neuroblastoma. The laboratory is currently focused on characterizing several transcriptional targets of MYCN which were identified by chromatin immunoprecipitation and microarray expression profiling. These include MDM2, the central inhibitor of the p53 tumor suppressor molecule. The laboratory is actively pursuing novel genetic and pharmacological methods of disrupting MDM2 function in neuroblastoma which can sensitize these tumors to p53 mediated apoptotic cell death. In vitro and in vivo transgenic mouse tumor models are used to develop preclinical data to validate these novel therapeutic approaches.
- Shohet, J.M., Hicks, M.J,, Plon, S.E., Susan Stuart, Si-Yi Chen, Malcolm Brenner and Jed G. Nuchtern, Minichromosome Maintenance Protein MCM7 is a Direct Target of the MYCN transcription Factor in Neuroblastoma. Cancer Research, 62, 1123-1128, Feb 15, 2002.
- Shohet, J.M., Pemberton, P., Carroll, M.C. Identification of a major binding site for complement C3 on the lgG heavy chain. Journal of Biological Chemistry, 268, 5866-71, 1993.
- Shohet, J.M., Bergemascini, L., Davis, A.E., Carroll, M.C. Localization of the covalent binding site of complement protein C3 on the lgG heavy chain. Journal of Biological Chemistry, 266:28, 18520-24, 1991.
- Slack A, Chen Z, Tonelli R, Pule M, Hunt L, Pession A, Shohet JM. The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma. Proc Natl Acad Sci USA, 102(3), 731-736, Jan 18, 2005.
- Slack A, Lozano G, Shohet JM. MDM2 as MYCN transcriptional target: implications for neuroblastoma pathogenesis. Cancer Letters, 2005 May 28; [Epub ahead of print]
- Tonelli R, Purgato S, Camerin C, Fronza R, Bologna F, Alboresi S, Franzoni M, Corradini R, Sforza S, Faccini A, Shohet J, Marchelli R, Pession A. Anti-gene Peptide Nucleic Acid (PNA) Specifically Inhibits MYCN Expression in Human Neuroblastoma Cells Leading to Cell-Growth Inhibition and Apoptosis. Mol Cancer Ther. 2005 May;4(5):779-86.
- Slack A and Shohet JM. MDM2 as a Critical Effector of the MYCN Oncogene in Tumorigenesis. Cell Cycle. 2005 Jul 28;4(7) [Epub ahead of print]