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    Rene Maehr PHD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    368 Plantation Street, AS7-2057
    Worcester MA 01605
    Phone508-856-3037
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

        Overview 
        Narrative
        Type 1 Diabetes (T1D) is the result of an autoimmune destruction of insulin producing, pancreatic beta cells. The events leading to the disease have usually occurred long before diagnosis and are based on complex interactions between genes and the environment. The currently available rodent models for T1D can only represent a limited number of patients leaving open the question how many different types of T1D exist. To overcome these difficulties and expand our understanding of T1D and other diseases targeting the immune system we are building in vitro models using human pluripotent stem cells. In those stem cell-based model systems genetic and developmental aspects of the disease can be elucidated. The long-term goal is to recapitulate the disease in a patient-specific manner and to identify novel treatment strategies.

        Rotation Projects
        A rotation project is available

        Post Docs
        A postdoctoral position is available


        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Chen YJ, Finkbeiner SR, Weinblatt D, Emmett MJ, Tameire F, Yousefi M, Yang C, Maehr R, Zhou Q, Shemer R, Dor Y, Li C, Spence JR, Stanger BZ. De Novo Formation of Insulin-Producing "Neo-ß Cell Islets" from Intestinal Crypts. Cell Rep. 2014 Mar 27; 6(6):1046-58.
          View in: PubMed
        2. Kearns NA, Genga RM, Enuameh MS, Garber M, Wolfe SA, Maehr R. Cas9 effector-mediated regulation of transcription and differentiation in human pluripotent stem cells. Development. 2014 Jan; 141(1):219-23.
          View in: PubMed
        3. Tajonar A, Maehr R, Hu G, Sneddon JB, Rivera-Feliciano J, Cohen DE, Elledge SJ, Melton DA. Brief Report: VGLL4 Is a Novel Regulator of Survival in Human Embryonic Stem Cells. Stem Cells. 2013 Dec; 31(12):2833-41.
          View in: PubMed
        4. Kearns NA, Genga RM, Ziller M, Kapinas K, Peters H, Brehm MA, Meissner A, Maehr R. Generation of organized anterior foregut epithelia from pluripotent stem cells using small molecules. Stem Cell Res. 2013 Nov; 11(3):1003-12.
          View in: PubMed
        5. Sherwood RI, Maehr R, Mazzoni EO, Melton DA. Wnt signaling specifies and patterns intestinal endoderm. Mech Dev. 2011 Sep-Dec; 128(7-10):387-400.
          View in: PubMed
        6. Maehr R. iPS cells in type 1 diabetes research and treatment. Clin Pharmacol Ther. 2011 May; 89(5):750-3.
          View in: PubMed
        7. Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW, Kim TK, Griffith EC, Waldon Z, Maehr R, Ploegh HL, Chowdhury S, Worley PF, Steen J, Greenberg ME. The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell. 2010 Mar 5; 140(5):704-16.
          View in: PubMed
        8. Niakan KK, Ji H, Maehr R, Vokes SA, Rodolfa KT, Sherwood RI, Yamaki M, Dimos JT, Chen AE, Melton DA, McMahon AP, Eggan K. Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal. Genes Dev. 2010 Feb 1; 24(3):312-26.
          View in: PubMed
        9. Maehr R, Chen S, Snitow M, Ludwig T, Yagasaki L, Goland R, Leibel RL, Melton DA. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci U S A. 2009 Sep 15; 106(37):15768-73.
          View in: PubMed
        10. Borowiak M, Maehr R, Chen S, Chen AE, Tang W, Fox JL, Schreiber SL, Melton DA. Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells. Cell Stem Cell. 2009 Apr 3; 4(4):348-58.
          View in: PubMed
        11. Chen S, Borowiak M, Fox JL, Maehr R, Osafune K, Davidow L, Lam K, Peng LF, Schreiber SL, Rubin LL, Melton D. A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat Chem Biol. 2009 Apr; 5(4):258-65.
          View in: PubMed
        12. Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol. 2008 Nov; 26(11):1269-75.
          View in: PubMed
        13. Gounaris E, Tung CH, Restaino C, Maehr R, Kohler R, Joyce JA, Ploegh HL, Plough HL, Barrett TA, Weissleder R, Khazaie K. Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth. PLoS One. 2008; 3(8):e2916.
          View in: PubMed
        14. Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol. 2008 Jul; 26(7):795-7.
          View in: PubMed
        15. Westbrook TF, Hu G, Ang XL, Mulligan P, Pavlova NN, Liang A, Leng Y, Maehr R, Shi Y, Harper JW, Elledge SJ. SCFbeta-TRCP controls oncogenic transformation and neural differentiation through REST degradation. Nature. 2008 Mar 20; 452(7185):370-4.
          View in: PubMed
        16. Ryu KY, Maehr R, Gilchrist CA, Long MA, Bouley DM, Mueller B, Ploegh HL, Kopito RR. The mouse polyubiquitin gene UbC is essential for fetal liver development, cell-cycle progression and stress tolerance. EMBO J. 2007 Jun 6; 26(11):2693-706.
          View in: PubMed
        17. Kumazaki K, Tirosh B, Maehr R, Boes M, Honjo T, Ploegh HL. AID-/-mus-/- mice are agammaglobulinemic and fail to maintain B220-CD138+ plasma cells. J Immunol. 2007 Feb 15; 178(4):2192-203.
          View in: PubMed
        18. Hang HC, Loureiro J, Spooner E, van der Velden AW, Kim YM, Pollington AM, Maehr R, Starnbach MN, Ploegh HL. Mechanism-based probe for the analysis of cathepsin cysteine proteases in living cells. ACS Chem Biol. 2006 Dec 20; 1(11):713-23.
          View in: PubMed
        19. Koch KS, Son KH, Maehr R, Pellicciotta I, Ploegh HL, Zanetti M, Sell S, Leffert HL. Immune-privileged embryonic Swiss mouse STO and STO cell-derived progenitor cells: major histocompatibility complex and cell differentiation antigen expression patterns resemble those of human embryonic stem cell lines. Immunology. 2006 Sep; 119(1):98-115.
          View in: PubMed
        20. Maehr R, Mintern JD, Herman AE, Lennon-Duménil AM, Mathis D, Benoist C, Ploegh HL. Cathepsin L is essential for onset of autoimmune diabetes in NOD mice. J Clin Invest. 2005 Oct; 115(10):2934-43.
          View in: PubMed
        21. Maehr R, Hang HC, Mintern JD, Kim YM, Cuvillier A, Nishimura M, Yamada K, Shirahama-Noda K, Hara-Nishimura I, Ploegh HL. Asparagine endopeptidase is not essential for class II MHC antigen presentation but is required for processing of cathepsin L in mice. J Immunol. 2005 Jun 1; 174(11):7066-74.
          View in: PubMed
        22. Maehr R, Kraus M, Ploegh HL. Mice deficient in invariant-chain and MHC class II exhibit a normal mature B2 cell compartment. Eur J Immunol. 2004 Aug; 34(8):2230-6.
          View in: PubMed
        23. van Swieten PF, Maehr R, van den Nieuwendijk AM, Kessler BM, Reich M, Wong CS, Kalbacher H, Leeuwenburgh MA, Driessen C, van der Marel GA, Ploegh HL, Overkleeft HS. Development of an isotope-coded activity-based probe for the quantitative profiling of cysteine proteases. Bioorg Med Chem Lett. 2004 Jun 21; 14(12):3131-4.
          View in: PubMed
        24. Schmidt-Supprian M, Tian J, Grant EP, Pasparakis M, Maehr R, Ovaa H, Ploegh HL, Coyle AJ, Rajewsky K. Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-kappaB activation. Proc Natl Acad Sci U S A. 2004 Mar 30; 101(13):4566-71.
          View in: PubMed
        25. Kocks C, Maehr R, Overkleeft HS, Wang EW, Iyer LK, Lennon-Dumenil AM, Ploegh HL, Kessler BM. Functional proteomics of the active cysteine protease content in Drosophila S2 cells. Mol Cell Proteomics. 2003 Nov; 2(11):1188-97.
          View in: PubMed
        26. Fiebiger E, Maehr R, Villadangos J, Weber E, Erickson A, Bikoff E, Ploegh HL, Lennon-Duménil AM. Invariant chain controls the activity of extracellular cathepsin L. J Exp Med. 2002 Nov 4; 196(9):1263-9.
          View in: PubMed
        27. Vugmeyster Y, Borodovsky A, Maurice MM, Maehr R, Furman MH, Ploegh HL. The ubiquitin-proteasome pathway in thymocyte apoptosis: caspase-dependent processing of the deubiquitinating enzyme USP7 (HAUSP). Mol Immunol. 2002 Nov; 39(7-8):431-41.
          View in: PubMed
        28. Lennon-Duménil AM, Bakker AH, Maehr R, Fiebiger E, Overkleeft HS, Rosemblatt M, Ploegh HL, Lagaudrière-Gesbert C. Analysis of protease activity in live antigen-presenting cells shows regulation of the phagosomal proteolytic contents during dendritic cell activation. J Exp Med. 2002 Aug 19; 196(4):529-40.
          View in: PubMed
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