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Jason Matthew Shohet MD, PhD

TitleAssociate Professor
InstitutionUniversity of Massachusetts Medical School
DepartmentPediatrics
Email
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentPediatrics

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentCancer Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program


    Collapse ORNG Applications 
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    Collapse Biography 
    Collapse education and training
    Reed College , Portland OregonBA06/1985Chemistry
    Boston University , Boston, MaMD/PhD07/1993
    Baylor College of Medicine, Houston, TexasPediatric Residency07/1995Pediatrics
    Baylor College of Medicine , Houston, TexasFellowship 09/1996Pediatric Oncology
    U.T. Southwestern Medical School, Dallas, TexasFellowship08/1999Pediatric Oncology

    Collapse Overview 
    Collapse overview

    As a pediatric oncologist, my research goals are to develop more effective and less toxic therapies for childhood cancers with a special focus on neuroblastoma. This MYCN-driven malignancy of the peripheral sympathetic nervous system accounts for 13% of all pediatric cancer deaths. I have recently relocated to assume the position as Division Chief for Pediatric Hematology/Oncology at University of Massachusetts Medical School in Worcester, Ma. This is after 19 years as co-chair of the Neuroblastoma Research program at Texas Children’s Cancer Center, Baylor College of Medicine. The UMass Medical School and UMass Memorial Clinical organizations provides exceptional support and research infrastructure for basic and translational efforts. I am an affiliated member of the Cancer Biology program, the MD, PhD program and the division of Molecular, Cell and Cancer Biology (MCCB). 

    A major focus of my laboratory is characterizing the role of MYCN in neuroblastoma pathogenesis and tumor stem cell biology. We have defined a novel tumor subpopulation meeting criteria as cancer stem cells or tumor initiating cells. That is the ability to self-renew, differentiate and recapitulate all the subsets of cells making up a complex tumor in vivo. We are further characterizing intra-tumor heterogeneity using single cell approaches.  

    As part of this work we have characterized multiple direct transcriptional targets of MYCN which are either destabilize p53 (e.g. MDM2) or alter transcriptional pathways to promote proliferation and inhibit apoptosis (e.g. MCM7 or mir-34a). This work has involved developing novel transgenic mouse models, optimized orthotopic xenografts and conditional cell lines for gain and loss of function studies of both microRNAs and coding genes. Our most recent efforts resulted in defining a novel direct binding interaction of MYCN with p53 that reveals a novel oncogenic function for MYCN as a direct transcriptional cofactor for p53.



    Collapse Rotation Projects

    Student rotation projects forcussed on cancer stem cells, chromatin profiling, and structural characterization of transcription factor/DNA interactions are available. 

    Our laboratory has a number of projects and opportunitys to learn in vivo tumor modeling and translation oncology research. 



    Collapse Post Docs

    We currently have a position open for a post-doc interested in cancer stem cell biology and structural biochemistry/ and modeling protein interations via cryo-EM. 




    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Agarwal S, Milazzo G, Rajapakshe K, Bernardi R, Chen Z, Eveline B, Koster J, Perini G, Coarfa C, Shohet JM. Correction: MYCN acts as a direct co-regulator of p53 in MYCN amplified neuroblastoma. Oncotarget. 2018 Jul 06; 9(52):30024. PMID: 30042831.
      View in: PubMed
    2. Agarwal S, Milazzo G, Rajapakshe K, Bernardi R, Chen Z, Barberi E, Koster J, Perini G, Coarfa C, Shohet JM. MYCN acts as a direct co-regulator of p53 in MYCN amplified neuroblastoma. Oncotarget. 2018 Apr 17; 9(29):20323-20338. PMID: 29755654.
      View in: PubMed
    3. Tomolonis JA, Agarwal S, Shohet JM. Neuroblastoma pathogenesis: deregulation of embryonic neural crest development. Cell Tissue Res. 2018 May; 372(2):245-262. PMID: 29222693.
      View in: PubMed
    4. Sun W, Rojas Y, Wang H, Yu Y, Wang Y, Chen Z, Rajapakshe K, Xu X, Huang W, Agarwal S, Patel RH, Woodfield S, Zhao Y, Jin J, Zhang H, Major A, Hicks MJ, Shohet JM, Vasudevan SA, Coarfa C, Yang J, Nuchtern JG. EWS-FLI1 and RNA helicase A interaction inhibitor YK-4-279 inhibits growth of neuroblastoma. Oncotarget. 2017 Nov 07; 8(55):94780-94792. PMID: 29212266.
      View in: PubMed
    5. Moreno-Smith M, Lakoma A, Chen Z, Tao L, Scorsone KA, Schild L, Aviles-Padilla K, Nikzad R, Zhang Y, Chakraborty R, Molenaar JJ, Vasudevan SA, Sheehan V, Kim ES, Paust S, Shohet JM, Barbieri E. p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy. Clin Cancer Res. 2017 Nov 01; 23(21):6629-6639. PMID: 28821555.
      View in: PubMed
    6. Van Goethem A, Yigit N, Moreno-Smith M, Vasudevan SA, Barbieri E, Speleman F, Shohet J, Vandesompele J, Van Maerken T. Dual targeting of MDM2 and BCL2 as a therapeutic strategy in neuroblastoma. Oncotarget. 2017 Aug 22; 8(34):57047-57057. PMID: 28915653.
      View in: PubMed
    7. Shohet J, Foster J. Neuroblastoma. BMJ. 2017 05 03; 357:j1863. PMID: 28468760.
      View in: PubMed
    8. Van Goethem A, Yigit N, Everaert C, Moreno-Smith M, Mus LM, Barbieri E, Speleman F, Mestdagh P, Shohet J, Van Maerken T, Vandesompele J. Depletion of tRNA-halves enables effective small RNA sequencing of low-input murine serum samples. Sci Rep. 2016 11 30; 6:37876. PMID: 27901112.
      View in: PubMed
    9. Ghaghada KB, Starosolski ZA, Lakoma A, Kaffes C, Agarwal S, Athreya KK, Shohet J, Kim E, Annapragada A. Heterogeneous Uptake of Nanoparticles in Mouse Models of Pediatric High-Risk Neuroblastoma. PLoS One. 2016; 11(11):e0165877. PMID: 27861510.
      View in: PubMed
    10. Zage PE, Whittle SB, Shohet JM. CD114: A New Member of the Neural Crest-Derived Cancer Stem Cell Marker Family. J Cell Biochem. 2017 02; 118(2):221-231. PMID: 27428599.
      View in: PubMed
    11. Agarwal S, Ghosh R, Chen Z, Lakoma A, Gunaratne PH, Kim ES, Shohet JM. Transmembrane adaptor protein PAG1 is a novel tumor suppressor in neuroblastoma. Oncotarget. 2016 Apr 26; 7(17):24018-26. PMID: 26993602.
      View in: PubMed
    12. Zhang S, Wei JS, Li SQ, Badgett TC, Song YK, Agarwal S, Coarfa C, Tolman C, Hurd L, Liao H, He J, Wen X, Liu Z, Thiele CJ, Westermann F, Asgharzadeh S, Seeger RC, Maris JM, Guidry Auvil JM, Smith MA, Kolaczyk ED, Shohet J, Khan J. MYCN controls an alternative RNA splicing program in high-risk metastatic neuroblastoma. Cancer Lett. 2016 Feb 28; 371(2):214-24. PMID: 26683771.
      View in: PubMed
    13. Bogen D, Wei JS, Azorsa DO, Ormanoglu P, Buehler E, Guha R, Keller JM, Mathews Griner LA, Ferrer M, Song YK, Liao H, Mendoza A, Gryder BE, Sindri S, He J, Wen X, Zhang S, Shern JF, Yohe ME, Taschner-Mandl S, Shohet JM, Thomas CJ, Martin SE, Ambros PF, Khan J. Aurora B kinase is a potent and selective target in MYCN-driven neuroblastoma. Oncotarget. 2015 Nov 03; 6(34):35247-62. PMID: 26497213.
      View in: PubMed
    14. Sun Y, Bell JL, Carter D, Gherardi S, Poulos RC, Milazzo G, Wong JW, Al-Awar R, Tee AE, Liu PY, Liu B, Atmadibrata B, Wong M, Trahair T, Zhao Q, Shohet JM, Haupt Y, Schulte JH, Brown PJ, Arrowsmith CH, Vedadi M, MacKenzie KL, Hüttelmaier S, Perini G, Marshall GM, Braithwaite A, Liu T. WDR5 Supports an N-Myc Transcriptional Complex That Drives a Protumorigenic Gene Expression Signature in Neuroblastoma. Cancer Res. 2015 Dec 01; 75(23):5143-54. PMID: 26471359.
      View in: PubMed
    15. Kim ES, Agarwal S, Shohet JM. G-CSF Is a Cancer Stem Cell-Specific Growth Factor-Response. Cancer Res. 2015 Sep 15; 75(18):3992. PMID: 26337907; PMCID: PMC4608385.
    16. Zhang L, Agarwal S, Shohet JM, Zage PE. CD114 Expression Mediates Melanoma Tumor Cell Growth and Treatment Resistance. Anticancer Res. 2015 Jul; 35(7):3787-92. PMID: 26124323.
      View in: PubMed
    17. Beckers A, Van Peer G, Carter DR, Gartlgruber M, Herrmann C, Agarwal S, Helsmoortel HH, Althoff K, Molenaar JJ, Cheung BB, Schulte JH, Benoit Y, Shohet JM, Westermann F, Marshall GM, Vandesompele J, De Preter K, Speleman F. MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma. Cancer Lett. 2015 Sep 28; 366(1):123-32. PMID: 26123663.
      View in: PubMed
    18. Yang J, AlTahan AM, Hu D, Wang Y, Cheng PH, Morton CL, Qu C, Nathwani AC, Shohet JM, Fotsis T, Koster J, Versteeg R, Okada H, Harris AL, Davidoff AM. The role of histone demethylase KDM4B in Myc signaling in neuroblastoma. J Natl Cancer Inst. 2015 Jun; 107(6):djv080. PMID: 25925418.
      View in: PubMed
    19. Agarwal S, Lakoma A, Chen Z, Hicks J, Metelitsa LS, Kim ES, Shohet JM. G-CSF Promotes Neuroblastoma Tumorigenicity and Metastasis via STAT3-Dependent Cancer Stem Cell Activation. Cancer Res. 2015 Jun 15; 75(12):2566-79. PMID: 25908586.
      View in: PubMed
    20. Rihani A, Van Goethem A, Ongenaert M, De Brouwer S, Volders PJ, Agarwal S, De Preter K, Mestdagh P, Shohet J, Speleman F, Vandesompele J, Van Maerken T. Genome wide expression profiling of p53 regulated miRNAs in neuroblastoma. Sci Rep. 2015 Mar 12; 5:9027. PMID: 25762502; PMCID: PMC4356961.
    21. Richter M, Dayaram T, Gilmartin AG, Ganji G, Pemmasani SK, Van Der Key H, Shohet JM, Donehower LA, Kumar R. WIP1 phosphatase as a potential therapeutic target in neuroblastoma. PLoS One. 2015; 10(2):e0115635. PMID: 25658463; PMCID: PMC4319922.
    22. Louis CU, Shohet JM. Neuroblastoma: molecular pathogenesis and therapy. Annu Rev Med. 2015; 66:49-63. PMID: 25386934.
      View in: PubMed
    23. Hsu DM, Shohet JM, Kim ES. In vivo Lineage-tracing Studies in a Cancer Stem Cell Population in Neuroblastoma. Bio Protoc. 2014 Apr 20; 4(8). PMID: 27540563.
      View in: PubMed
    24. Stricker TP, Morales La Madrid A, Chlenski A, Guerrero L, Salwen HR, Gosiengfiao Y, Perlman EJ, Furman W, Bahrami A, Shohet JM, Zage PE, Hicks MJ, Shimada H, Suganuma R, Park JR, So S, London WB, Pytel P, Maclean KH, Cohn SL. Validation of a prognostic multi-gene signature in high-risk neuroblastoma using the high throughput digital NanoString nCounterâ„¢ system. Mol Oncol. 2014 May; 8(3):669-78. PMID: 24560446; PMCID: PMC4004665.
    25. Barone G, Tweddle DA, Shohet JM, Chesler L, Moreno L, Pearson AD, Van Maerken T. MDM2-p53 interaction in paediatric solid tumours: preclinical rationale, biomarkers and resistance. Curr Drug Targets. 2014 Jan; 15(1):114-23. PMID: 24387312.
      View in: PubMed
    26. Barbieri E, De Preter K, Capasso M, Chen Z, Hsu DM, Tonini GP, Lefever S, Hicks J, Versteeg R, Pession A, Speleman F, Kim ES, Shohet JM. Histone chaperone CHAF1A inhibits differentiation and promotes aggressive neuroblastoma. Cancer Res. 2014 Feb 01; 74(3):765-74. PMID: 24335960.
      View in: PubMed
    27. Barbieri E, De Preter K, Capasso M, Johansson P, Man TK, Chen Z, Stowers P, Tonini GP, Speleman F, Shohet JM. A p53 drug response signature identifies prognostic genes in high-risk neuroblastoma. PLoS One. 2013; 8(11):e79843. PMID: 24348903; PMCID: PMC3865347.
    28. Hsu DM, Agarwal S, Benham A, Coarfa C, Trahan DN, Chen Z, Stowers PN, Courtney AN, Lakoma A, Barbieri E, Metelitsa LS, Gunaratne P, Kim ES, Shohet JM. G-CSF receptor positive neuroblastoma subpopulations are enriched in chemotherapy-resistant or relapsed tumors and are highly tumorigenic. Cancer Res. 2013 Jul 01; 73(13):4134-46. PMID: 23687340.
      View in: PubMed
    29. Shohet JM. Redefining functional MYCN gene signatures in neuroblastoma. Proc Natl Acad Sci U S A. 2012 Nov 20; 109(47):19041-2. PMID: 23139408.
      View in: PubMed
    30. Ghosh R, Singh LC, Shohet JM, Gunaratne PH. A gold nanoparticle platform for the delivery of functional microRNAs into cancer cells. Biomaterials. 2013 Jan; 34(3):807-16. PMID: 23111335.
      View in: PubMed
    31. Shohet JM, Ghosh R, Coarfa C, Ludwig A, Benham AL, Chen Z, Patterson DM, Barbieri E, Mestdagh P, Sikorski DN, Milosavljevic A, Kim ES, Gunaratne PH. A genome-wide search for promoters that respond to increased MYCN reveals both new oncogenic and tumor suppressor microRNAs associated with aggressive neuroblastoma. Cancer Res. 2011 Jun 01; 71(11):3841-51. PMID: 21498633.
      View in: PubMed
    32. Patterson DM, Gao D, Trahan DN, Johnson BA, Ludwig A, Barbieri E, Chen Z, Diaz-Miron J, Vassilev L, Shohet JM, Kim ES. Effect of MDM2 and vascular endothelial growth factor inhibition on tumor angiogenesis and metastasis in neuroblastoma. Angiogenesis. 2011 Sep; 14(3):255-66. PMID: 21484514.
      View in: PubMed
    33. Patterson DM, Shohet JM, Kim ES. Preclinical models of pediatric solid tumors (neuroblastoma) and their use in drug discovery. Curr Protoc Pharmacol. 2011 Mar; Chapter 14:Unit 14.17. PMID: 21935903.
      View in: PubMed
    34. Russell H, Shohet JM. Pediatric oncology: G-CSF counteracts chemotherapy toxicity in neuroblastoma. Nat Rev Clin Oncol. 2011 Jan; 8(1):6-8. PMID: 21102531.
      View in: PubMed
    35. Kim E, Shohet J. Targeted molecular therapy for neuroblastoma: the ARF/MDM2/p53 axis. J Natl Cancer Inst. 2009 Nov 18; 101(22):1527-9. PMID: 19903809.
      View in: PubMed
    36. Chen Z, Lin Y, Barbieri E, Burlingame S, Hicks J, Ludwig A, Shohet JM. Mdm2 deficiency suppresses MYCN-Driven neuroblastoma tumorigenesis in vivo. Neoplasia. 2009 Aug; 11(8):753-62. PMID: 19649205; PMCID: PMC2713395.
    37. Slack AD, Chen Z, Ludwig AD, Hicks J, Shohet JM. MYCN-directed centrosome amplification requires MDM2-mediated suppression of p53 activity in neuroblastoma cells. Cancer Res. 2007 Mar 15; 67(6):2448-55. PMID: 17363562.
      View in: PubMed
    38. Barbieri E, Mehta P, Chen Z, Zhang L, Slack A, Berg S, Shohet JM. MDM2 inhibition sensitizes neuroblastoma to chemotherapy-induced apoptotic cell death. Mol Cancer Ther. 2006 Sep; 5(9):2358-65. PMID: 16985070.
      View in: PubMed
    39. Slack A, Lozano G, Shohet JM. MDM2 as MYCN transcriptional target: implications for neuroblastoma pathogenesis. Cancer Lett. 2005 Oct 18; 228(1-2):21-7. PMID: 15927364.
      View in: PubMed
    40. Slack A, Shohet JM. MDM2 as a critical effector of the MYCN oncogene in tumorigenesis. Cell Cycle. 2005 Jul; 4(7):857-60. PMID: 15917661.
      View in: PubMed
    41. Tonelli R, Purgato S, Camerin C, Fronza R, Bologna F, Alboresi S, Franzoni M, Corradini R, Sforza S, Faccini A, Shohet JM, Marchelli R, Pession A. Anti-gene peptide nucleic acid specifically inhibits MYCN expression in human neuroblastoma cells leading to cell growth inhibition and apoptosis. Mol Cancer Ther. 2005 May; 4(5):779-86. PMID: 15897242.
      View in: PubMed
    42. Vasudevan SA, Nuchtern JG, Shohet JM. Gene profiling of high risk neuroblastoma. World J Surg. 2005 Mar; 29(3):317-24. PMID: 15706435.
      View in: PubMed
    43. 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 U S A. 2005 Jan 18; 102(3):731-6. PMID: 15644444; PMCID: PMC545522.
    44. Shohet JM, Hicks MJ, Plon SE, Burlingame SM, Stuart S, Chen SY, Brenner MK, Nuchtern JG. Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Cancer Res. 2002 Feb 15; 62(4):1123-8. PMID: 11861392.
      View in: PubMed
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