Hamid Mattoo
Ragon Institute of MGH, MIT and Harvard
Immunoglobulin ECellMolecular biologyCytotoxic T cellAntibodyTranscriptomeImmunologyT cellB cellDiseaseGranzyme AIgG4-related diseaseFibrosisImmunoglobulin GPopulationCancer researchMedicineBiologyImmune systemCell biology
49Publications
21H-index
2,333Citations
Publications 45
Newest
#1Vinay S. Mahajan (Ragon Institute of MGH, MIT and Harvard)H-Index: 23
#1V. S. Mahajan (University of Pittsburgh)
Last. J Das (University of Pittsburgh)H-Index: 1
view all 8 authors...
T follicular helper (Tfh) cells play a critical role in T-dependent humoral immune responses. While genetic programs controlling Tfh cell differentiation have been extensively studied using murine models, studies in humans have been hampered by the lack of a robust in vitro differentiation system for Tfh cells. We characterized epigenomic landscapes across stages of Tfh cell differentiation in a healthy human tonsil using ATAC-Seq and CUT&RUN for selected histone modifications. We combined these...
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#1Vinay S. Mahajan (Brigham and Women's Hospital)H-Index: 23
#2Hamid Mattoo (Ragon Institute of MGH, MIT and Harvard)H-Index: 21
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 11 authors...
The B1 and B2 lineages of B cells contribute to protection from pathogens in distinct ways. The role of the DNA CpG methylome in specifying these two B-cell fates is still unclear. Here we profile the CpG modifications and transcriptomes of peritoneal B1a and follicular B2 cells, as well as their respective proB cell precursors in the fetal liver and adult bone marrow from wild-type and CD19-Cre Dnmt3a floxed mice lacking DNMT3A in the B lineage. We show that an underlying foundational CpG methy...
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#1Cory A. Perugino (Harvard University)H-Index: 13
#2Naoki Kaneko (Kyushu University)H-Index: 10
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 28 authors...
Abstract Background IgG4-related disease (IgG4-RD) is an immune-mediated fibrotic disorder that has been linked to CD4+ cytotoxic T lymphocytes (CD4+CTLs). The effector phenotype of CD4+CTLs, the relevance of both CD8+ cytotoxic T lymphocytes (CD8+CTLs) and of apoptotic cell death remain undefined in IgG4-RD. Objective The goals of this study were to define CD4+CTL heterogeneity, characterize the CD8+CTL response in the blood and in lesions, and determine whether enhanced apoptosis may contribut...
9 CitationsSource
#1Takashi MaeharaH-Index: 20
#2Naoki Kaneko (MIT: Massachusetts Institute of Technology)H-Index: 1
Last. Shiv Pillai (MIT: Massachusetts Institute of Technology)H-Index: 50
view all 16 authors...
Systemic sclerosis (SSc) is an autoimmune fibrotic disease whose pathogenesis is poorly understood and lacks effective therapies. We undertook quantitative analyses of T cell infiltrates in the skin of thirty-five untreated patients with early diffuse SSc and here show that CD4+ cytotoxic T cells and CD8+ T cells contribute prominently to these infiltrates. We also observed an accumulation of apoptotic cells in SSc tissues, suggesting that recurring cell death may contribute to tissue damage and...
23 CitationsSource
#1Vinay S. Mahajan (Ragon Institute of MGH, MIT and Harvard)H-Index: 23
#2Hamid Mattoo (Ragon Institute of MGH, MIT and Harvard)H-Index: 21
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 11 authors...
We show that DNA methylation is a layered process in B lymphocytes. An underlying foundational methylome is stably established during B lineage commitment and overlaid with a DNMT3A-maintained dynamic methylome which is sculpted in distinct ways in B1 and B2 B cells during B cell development. An engineered loss of DNMT3A after commitment to the B lineage unmasks a foundational methylome that is shared in both B1 and B2 sub-lineages. The dynamic methylome is comprised of novel enhancers whose met...
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#1Emanuel Della-Torre (UniSR: Vita-Salute San Raffaele University)H-Index: 25
#2Elena Rigamonti (UniSR: Vita-Salute San Raffaele University)H-Index: 9
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 19 authors...
Background IgG4-related disease (IgG4-RD) is a fibroinflammatory condition marked by rapid clinical improvement after selective depletion of B lymphocytes with rituximab. This feature suggests that B cells might participate in fibrogenesis and wound healing. Objective In the present work we aimed to demonstrate that B lymphocytes contribute directly to tissue fibrosis in patients with IgG4-RD. Methods Total circulating CD19+ B lymphocytes, naive B cells, memory B cells, or plasmablasts from pati...
25 CitationsSource
#1John H. Newman (Vandy: Vanderbilt University)H-Index: 58
#2Shaver A (Vandy: Vanderbilt University)H-Index: 1
Last. John A. Phillips (Vandy: Vanderbilt University)H-Index: 66
view all 22 authors...
BACKGROUND: Family screening of a 48-year-old male with recently diagnosed IgG4-related disease (IgG4-RD) revealed unanticipated elevations in plasma IgG4 in his two healthy teenaged sons. METHODS: We performed gene sequencing, immune cell studies, HLA typing, and analyses of circulating cytotoxic CD4+ T lymphocytes and plasmablasts to seek clues to pathogenesis. DNA from a separate cohort of 99 patients with known IgG4-RD was also sequenced for the presence of genetic variants in a specific gen...
3 CitationsSource
#1Vinay S. Mahajan (Brigham and Women's Hospital)H-Index: 23
#2Faisal Alsufyani (Ragon Institute of MGH, MIT and Harvard)H-Index: 2
Last. Shiv Pillai (Harvard University)H-Index: 50
view all 5 authors...
: We used Casd1-deficient mice to confirm that this enzyme is responsible for 9-O-acetylation of sialic acids in vivo. We observed a complete loss of 9-O-acetylation of sialic acid on the surface of myeloid, erythroid and CD4+ T cells in Casd1-deficient mice. Although 9-O-acetylation of sialic acids on multiple hematopoietic lineages was lost, there were no obvious defects in hematopoiesis. Interestingly, erythrocytes from Casd1-deficient mice also lost reactivity to TER-119, a rat monoclonal an...
4 CitationsSource
#1Cory A. Perugino (Harvard University)H-Index: 13
#2Sultan B. AlSalem (KSU: King Saud University)H-Index: 1
Last. Shiv Pillai (Harvard University)H-Index: 50
view all 13 authors...
Background The antigenic trigger that drives expansion of circulating plasmablasts and CD4+ cytotoxic T cells in patients with IgG4-related disease (IgG4-RD) is presently unknown. Objective We sought to sequence immunoglobulin genes from single-cell clones of dominantly expanded plasmablasts and generate recombinant human mAbs to identify relevant antigens in patients with IgG4-RD by using mass spectrometry. Methods Paired heavy and light chain cDNAs from dominant plasmablast clones were express...
54 CitationsSource
#1Faisal Alsufyani (Ragon Institute of MGH, MIT and Harvard)H-Index: 2
#2Hamid Mattoo (Ragon Institute of MGH, MIT and Harvard)H-Index: 21
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 8 authors...
The Mst1 and 2 cytosolic serine/threonine protein kinases are the mammalian orthologs of the Drosophila Hippo protein. Mst1 has been shown previously to participate in T-cell and B-cell trafficking and the migration of lymphocytes into secondary lymphoid organs in a cell-intrinsic manner. We show here that the absence of Mst1 alone only modestly impacts B cell homing to lymph nodes. The absence of both Mst1 and 2 in hematopoietic cells results in relatively normal B cell development in the bone ...
6 CitationsSource