Michael A Brehm

Summary

Affiliation: University of Massachusetts Medical School
Country: USA

Publications

  1. pmc Maturation-dependent licensing of naive T cells for rapid TNF production
    Bhavana Priyadharshini
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    PLoS ONE 5:e15038. 2010
  2. pmc Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγ null mice is enhanced by transgenic expression of membrane-bound human SCF
    Michael A Brehm
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Blood 119:2778-88. 2012
  3. doi request reprint Human allograft rejection in humanized mice: a historical perspective
    Michael A Brehm
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Cell Mol Immunol 9:225-31. 2012
  4. pmc Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice
    Michael A Brehm
    Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Diabetes 59:2265-70. 2010
  5. pmc Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation
    Michael A Brehm
    Diabetes Division, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Clin Immunol 135:84-98. 2010
  6. pmc Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Blood 109:819-26. 2007
  7. pmc TLR agonists prevent the establishment of allogeneic hematopoietic chimerism in mice treated with costimulation blockade
    David M Miller
    Division of Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 182:5547-59. 2009
  8. ncbi request reprint Direct visualization of cross-reactive effector and memory allo-specific CD8 T cells generated in response to viral infections
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 170:4077-86. 2003
  9. pmc CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infections
    Markus Cornberg
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 184:2825-38. 2010
  10. pmc Idd loci synergize to prolong islet allograft survival induced by costimulation blockade in NOD mice
    Julie Mangada
    Program in Immunology and Virology, The University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Diabetes 58:165-73. 2009

Collaborators

Detail Information

Publications49

  1. pmc Maturation-dependent licensing of naive T cells for rapid TNF production
    Bhavana Priyadharshini
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    PLoS ONE 5:e15038. 2010
    ..Together, these findings suggest that TNF expression by naïve T cells is regulated via a gradual licensing process that requires functional maturation in peripheral lymphoid organs...
  2. pmc Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγ null mice is enhanced by transgenic expression of membrane-bound human SCF
    Michael A Brehm
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Blood 119:2778-88. 2012
    ..These data provide a new immunodeficient mouse model that does not require irradiation preconditioning for human HSC engraftment and immune system development...
  3. doi request reprint Human allograft rejection in humanized mice: a historical perspective
    Michael A Brehm
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Cell Mol Immunol 9:225-31. 2012
    ..Here, we present a historical perspective on the study of allograft rejection in humanized mice and discuss the use of these novel model systems in transplant biology...
  4. pmc Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice
    Michael A Brehm
    Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Diabetes 59:2265-70. 2010
    ..To create an immunodeficient mouse model that spontaneously develops hyperglycemia to serve as a diabetic host for human islets and stem cell-derived beta-cells in the absence or presence of a functional human immune system...
  5. pmc Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation
    Michael A Brehm
    Diabetes Division, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Clin Immunol 135:84-98. 2010
    ..Our data define key parameters for establishing humanized mouse models to study human immunity...
  6. pmc Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Blood 109:819-26. 2007
    ..We conclude that rapid production of TNF-alpha can be used to quantify naive alloreactive T cells, that it is abrogated after the induction of tolerance, and that it is a potential tool to predict allograft rejection...
  7. pmc TLR agonists prevent the establishment of allogeneic hematopoietic chimerism in mice treated with costimulation blockade
    David M Miller
    Division of Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 182:5547-59. 2009
    ..These data suggest that distinct but overlapping cellular and molecular mechanisms control the ability of TLR agonists to block tolerance induction to hematopoietic and skin allografts in mice treated with costimulation blockade...
  8. ncbi request reprint Direct visualization of cross-reactive effector and memory allo-specific CD8 T cells generated in response to viral infections
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 170:4077-86. 2003
    ..Mice previously infected with LCMV and harboring allo-specific memory T cells were refractory to the induction of tolerance to allogeneic skin grafts...
  9. pmc CD8 T cell cross-reactivity networks mediate heterologous immunity in human EBV and murine vaccinia virus infections
    Markus Cornberg
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 184:2825-38. 2010
    ..Defining such cross-reactive networks between commonly encountered human pathogens may facilitate the design of vaccines...
  10. pmc Idd loci synergize to prolong islet allograft survival induced by costimulation blockade in NOD mice
    Julie Mangada
    Program in Immunology and Virology, The University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Diabetes 58:165-73. 2009
    ..However, costimulation blockade-based tolerance protocols have failed in prolonging islet allograft survival in NOD mice...
  11. ncbi request reprint TLR agonists abrogate costimulation blockade-induced prolongation of skin allografts
    Thomas B Thornley
    Division of Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 176:1561-70. 2006
    ..We conclude that TLR signaling abrogates the effects of costimulation blockade by preventing alloreactive CD8+ T cell apoptosis through a mechanism not dependent on TNFR2 or IL-12R signaling...
  12. ncbi request reprint Rapid conversion of effector mechanisms from NK to T cells during virus-induced lysis of allogeneic implants in vivo
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, 01655, USA
    J Immunol 174:6663-71. 2005
    ..This rapid generation of allospecific CTL activity during a viral infection preceded the peak of viral epitope-specific T cell responses, as detected by in vivo or in vitro cytotoxicity assays...
  13. pmc TLR agonists abrogate co-stimulation blockade-induced mixed chimerism and transplantation tolerance
    David M Miller
    Department of Medicine, Division of Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Ann N Y Acad Sci 1150:149-51. 2008
    ....
  14. ncbi request reprint Preapoptotic phenotype of viral epitope-specific CD8 T cells precludes memory development and is an intrinsic property of the epitope
    Xiaoting Z Wang
    Program in Immunology and Virology, Department of Pathology, University of Massachusetts Medical School, Worcester 01655, USA
    J Immunol 173:5138-47. 2004
    ..The tissue-dependent and epitope-dependent preapoptotic state correlated with reduced expression of IL-7Ralpha...
  15. pmc Narrowed TCR repertoire and viral escape as a consequence of heterologous immunity
    Markus Cornberg
    Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School UMMS, Worcester, Massachusetts 01655, USA
    J Clin Invest 116:1443-56. 2006
    ..This has implications for the design of peptide-based vaccines, which might unintentionally prime for skewed TCR responses to cross-reactive epitopes...
  16. ncbi request reprint Type 1 IFN mediates cross-talk between innate and adaptive immunity that abrogates transplantation tolerance
    Thomas B Thornley
    Department of Medicine, Division of Diabetes, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 179:6620-9. 2007
    ..Blocking of type 1 IFN-dependent pathways in patients may improve allograft survival in the presence of exogenous TLR ligands...
  17. pmc Protection against vaccinia virus challenge by CD8 memory T cells resolved by molecular mimicry
    Markus Cornberg
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Virol 81:934-44. 2007
    ....
  18. ncbi request reprint Development of novel major histocompatibility complex class I and class II-deficient NOD-SCID IL2R gamma chain knockout mice for modeling human xenogeneic graft-versus-host disease
    Steve Pino
    Department of Medicine, The University of Massachusetts Medical School, Worcester, MA, USA
    Methods Mol Biol 602:105-17. 2010
    ....
  19. pmc Heterologous immunity between viruses
    Raymond M Welsh
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunol Rev 235:244-66. 2010
    ..We propose that heterologous immunity is an important factor in resistance to and variations of human viral infections and that issues of heterologous immunity should be considered in the design of vaccines...
  20. pmc Bi-specific MHC heterodimers for characterization of cross-reactive T cells
    Zu T Shen
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 285:33144-53. 2010
    ..A similar strategy could be used to develop reagents to analyze cross-reactive T cell responses in humans...
  21. pmc CHOP mediates endoplasmic reticulum stress-induced apoptosis in Gimap5-deficient T cells
    Steven C Pino
    Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS ONE 4:e5468. 2009
    ..These findings indicate a direct relationship between Gimap5 and the maintenance of ER homeostasis in the survival of T cells...
  22. ncbi request reprint Rapid production of TNF-alpha following TCR engagement of naive CD8 T cells
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 175:5043-9. 2005
    ....
  23. ncbi request reprint Tec kinases Itk and Rlk are required for CD8+ T cell responses to virus infection independent of their role in CD4+ T cell help
    Luana O Atherly
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 176:1571-81. 2006
    ..These defects cannot be rescued by providing virus-specific CD4(+) T cell help, thereby substantiating the important role of Tec kinases in CD8(+) T cell signaling...
  24. ncbi request reprint Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulation
    Sung Kwon Kim
    Department of Pathology, University of Massachusetts, Worcester, MA 01655, USA
    J Immunol 169:90-8. 2002
    ..Thus, depending on the pathogen and the sequence of infection, a heterologous agent may selectively stimulate the memory pool in patterns consistent with heterologous immunity...
  25. ncbi request reprint Memory of mice and men: CD8+ T-cell cross-reactivity and heterologous immunity
    Liisa K Selin
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunol Rev 211:164-81. 2006
    ....
  26. ncbi request reprint CD8 memory T cells: cross-reactivity and heterologous immunity
    Liisa K Selin
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Semin Immunol 16:335-47. 2004
    ..Here we discuss examples of altered viral pathogenesis occurring as a consequence of heterologous T cell immunity and propose models for the maintenance of a dynamic pool of memory cells...
  27. pmc Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance
    Ian A York
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Proc Natl Acad Sci U S A 103:9202-7. 2006
    ..Moreover, peptide trimming and the resulting abundance of peptide-MHC complexes are dominant factors in establishing immunodominance...
  28. ncbi request reprint CD8 T cell responses to viral infections in sequence
    Michael A Brehm
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Cell Microbiol 6:411-21. 2004
    ..Here we will describe the characteristics of CD8 T cells and the dynamics of their response to heterologous viral infections in sequence...
  29. ncbi request reprint Virus-specific CD8 T cells in peripheral tissues are more resistant to apoptosis than those in lymphoid organs
    Xiaoting Z Wang
    Department of Pathology, University of Massachusetts Medical School, Worcester 01655, USA
    Immunity 18:631-42. 2003
    ..This may contribute to the survival of nondividing peripheral memory T cells, enabling them to efficiently function without being driven into apoptosis...
  30. pmc Advancing animal models of human type 1 diabetes by engraftment of functional human tissues in immunodeficient mice
    Michael A Brehm
    University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, Massachusetts, USA
    Cold Spring Harb Perspect Med 2:a007757. 2012
    ..With this, these so-called "humanized mice" are currently being used as a preclinical bridge to facilitate identification and translation of novel discoveries to clinical settings...
  31. ncbi request reprint Heterologous immunity and the CD8 T cell network
    Liisa K Selin
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Springer Semin Immunopathol 24:149-68. 2002
  32. ncbi request reprint Frontiers in nephrology: heterologous immunity, T cell cross-reactivity, and alloreactivity
    Liisa K Selin
    Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Am Soc Nephrol 18:2268-77. 2007
    ....
  33. pmc Salicylate prevents virus-induced type 1 diabetes in the BBDR rat
    Chaoxing Yang
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS ONE 8:e78050. 2013
    ..The ability of salicylate to prevent diabetes in this robust animal model demonstrates its potential use to prevent or attenuate human autoimmune diabetes. ..
  34. pmc Humanized mice for the study of type 1 and type 2 diabetes
    Dale L Greiner
    University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Ann N Y Acad Sci 1245:55-8. 2011
    ..The availability of immunodeficient mice engrafted with functional human immune systems and islets permits in vivo study of human diabetes without putting patients at risk...
  35. pmc T-cell activation and transplantation tolerance
    Bhavana Priyadharshini
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Transplant Rev (Orlando) 26:212-22. 2012
    ....
  36. pmc Humanized mouse models to study human diseases
    Michael A Brehm
    Diabetes Division, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Curr Opin Endocrinol Diabetes Obes 17:120-5. 2010
    ..Update on humanized mouse models and their use in biomedical research...
  37. ncbi request reprint Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity
    Melissa Woelfel
    Department of Pathology, Immunology and Virology Program, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 177:3814-20. 2006
    ..Thus, the MC159-Tg mice provide a model to study the effects of PCD in immune responses without hampering other important lymphocyte functions...
  38. ncbi request reprint An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia
    Birgit Knoechel
    1 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 2 Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA 3 Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA 4 Division of Hematology Oncology, Boston Children s Hospital and Harvard Medical School, Boston, Massachusetts, USA 5
    Nat Genet 46:364-70. 2014
    ..Our findings establish a role for epigenetic heterogeneity in leukemia resistance that may be addressed by incorporating epigenetic modulators in combination therapy. ..
  39. ncbi request reprint c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells
    Justine E Roderick
    Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA
    Blood 123:1040-50. 2014
    ..These findings demonstrate a critical role for c-Myc in LIC maintenance and provide evidence that MYC inhibition may be an effective therapy for relapsed/IF T-ALL patients. ..
  40. pmc Humanized mice for the study of infectious diseases
    Michael A Brehm
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, United States
    Curr Opin Immunol 25:428-35. 2013
    ..Recent advances in the development of humanized mice have allowed in vivo studies of multiple human infectious agents providing novel insights into their pathogenesis that was otherwise not possible. ..
  41. pmc Dynamic glucoregulation and mammalian-like responses to metabolic and developmental disruption in zebrafish
    Agata Jurczyk
    University of Massachusetts Medical School, Diabetes Center of Excellence, 373 Plantation Street, Suite 218, Worcester, MA 01605, USA
    Gen Comp Endocrinol 170:334-45. 2011
    ..In summary, we identify mechanisms of glucoregulation in zebrafish embryos that are conserved with embryonic and adult mammals. These observations justify use of this model in mechanistic studies of human metabolic disease...
  42. pmc Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice
    Smita Jaiswal
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA
    Immunology 136:334-43. 2012
    ..The BLT-NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections...
  43. ncbi request reprint T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens
    Michael A Brehm
    Department of Pathology and Progranm in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Nat Immunol 3:627-34. 2002
    ..Thus, immunodominance is a function of the host's previous exposure to unrelated pathogens, and this may have an impact on protective immunity and immunopathology...
  44. ncbi request reprint Engrafted human cells generate adaptive immune responses to Mycobacterium bovis BCG infection in humanized mice
    Jinhee Lee
    Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
    BMC Immunol 14:53. 2013
    ..1 (NSG-A2) to generate NSG-A2-BLT mice and characterized their human immune response to Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection to assess the utility of this model for investigating human TB...
  45. ncbi request reprint Graded Levels of IRF4 Regulate CD8+ T Cell Differentiation and Expansion, but Not Attrition, in Response to Acute Virus Infection
    Ribhu Nayar
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655 and
    J Immunol 192:5881-93. 2014
    ..These data indicate that IRF4 is a key component that translates the strength of TCR signaling into a graded response of virus-specific CD8(+) T cells. ..
  46. pmc Durable knockdown and protection from HIV transmission in humanized mice treated with gel-formulated CD4 aptamer-siRNA chimeras
    Lee Adam Wheeler
    Program in Cellular and Molecular Medicine, Boston Children s Hospital, Boston, Massachusetts, USA
    Mol Ther 21:1378-89. 2013
    ..CD4-AsiCs targeting gag/vif provided some protection when administered only after exposure. These data suggest that CD4-AsiCs are a promising approach for developing an HIV microbicide. ..
  47. pmc Overcoming current limitations in humanized mouse research
    Michael A Brehm
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester
    J Infect Dis 208:S125-30. 2013
    ..This article provides an overview of some of the emerging models of humanized mice, their use in the study of infectious diseases, and some of the remaining limitations that are currently being addressed. ..
  48. ncbi request reprint Generation of organized anterior foregut epithelia from pluripotent stem cells using small molecules
    Nicola A Kearns
    Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA
    Stem Cell Res 11:1003-12. 2013
    ..Finally, we show that the directed differentiation protocol can be used to generate AFE from human PSCs. Thus, this work both broadens the range of PSC-derived AFE tissues and creates a platform enabling the study of AFE disorders. ..
  49. ncbi request reprint Partial versus full allogeneic hemopoietic chimerization is a preferential means to inhibit type 1 diabetes as the latter induces generalized immunosuppression
    David V Serreze
    The Jackson Laboratory, Bar Harbor, ME 04609, USA
    J Immunol 177:6675-84. 2006
    ....