- T-cell and B-cell Immunology
- RNA modifications and cancer
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- CAR-T cell therapy research
- Extracellular vesicles in disease
- Single-cell and spatial transcriptomics
- COVID-19 Clinical Research Studies
- Mast cells and histamine
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- IL-33, ST2, and ILC Pathways
- Asthma and respiratory diseases
- Immune responses and vaccinations
- RNA regulation and disease
Ragon Institute of MGH, MIT and Harvard
2019-2021
Broad Institute
2019-2021
Koch Institute for Integrative Cancer Research At MIT
2020-2021
IIT@MIT
2021
Allen Institute
2021
Massachusetts Institute of Technology
2019-2020
University of Pennsylvania
2015
Institute of Molecular Biology and Biophysics
2015
There is pressing urgency to understand the pathogenesis of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme (ACE2), and in concert with host proteases, principally transmembrane serine protease (TMPRSS2), promotes cellular entry. The cell subsets targeted by tissues factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, mouse...
Mast cells in type 2 airway inflammation exhibit heterogeneous inflammation-associated phenotypes and proliferate situ.
Germinal centers (GCs) are the site of immunoglobulin somatic hypermutation and affinity maturation, processes essential to an effective antibody response. The formation GCs has been studied in detail, but less is known about what leads their regression eventual termination, factors that ultimately limit extent which antibodies mature within a single reaction. We show contraction immunization-induced immediately preceded by acute surge GC-resident Foxp3+ T cells, attributed at least partly...
There is pressing urgency to better understand the pathogenesis of severe acute respiratory syndrome (SARS) coronavirus (CoV) clade SARS-CoV-2. SARS-CoV-2, like SARS-CoV, utilizes ACE2 bind host cells. While initial SARS-CoV-2 cell entry and infection depend on in concert with protease TMPRSS2 for spike (S) protein activation, specific subsets targeted by tissues, factors that regulate expression, remain unknown. Here, we leverage human non-human primate (NHP) single-cell RNA-sequencing...
Significance Alternative splicing is a key mechanism for gene regulation that regulated in response to developmental and antigen signaling T cells. However, the extent mechanisms of splicing, particularly during T-cell development, have not been well characterized. Here we demonstrate expression RNA binding protein CELF2 (CUGBP, Elav-like family member 2) increased through combined transcription mRNA stability. This increase drives widespread changes cultured cells correlates with...
During affinity maturation, germinal center (GC) B cells alternate between proliferation and somatic hypermutation in the dark zone (DZ) affinity-dependent selection light (LZ). This anatomical segregation imposes that vigorous allows clonal expansion of positively selected GC takes place ostensibly absence signals triggered LZ, as if by “inertia.” We find such inertial cycles specifically require cell cycle regulator cyclin D3. Cyclin D3 dose-dependently controls extent to which proliferate...
HnRNP L is a ubiquitous splicing-regulatory protein that critical for the development and function of mammalian T cells. Previous work has identified few targets hnRNP L-dependent alternative splicing in cells described transcriptome-wide association with RNA. However, comprehensive analysis impact on mRNA expression remains lacking. Here we use next-generation sequencing to identify transcriptome changes upon depletion model T-cell line. We demonstrate primarily regulates cassette-type...
ABSTRACT Maintenance of pluripotency and specification towards a new cell fate are both dependent on precise interactions between extrinsic signals transcriptional epigenetic regulators. Directed methylation cytosines by the de novo methyltransferases DNMT3A DNMT3B plays an important role in facilitating proper differentiation, whereas DNMT1 is essential for maintaining global levels all types. Here, we generated single-cell mRNA expression data from wild-type, DNMT3A, DNMT3A/3B knockout...
Abstract During affinity maturation, germinal center (GC) B cells alternate between proliferation and so-matic hypermutation in the dark zone (DZ) affinity-dependent selection light (LZ). This anatomical segregation imposes that vigorous allows clonal expansion of positively-selected GC takes place ostensibly absence signals triggered LZ, as if by “inertia.” We find such inertial cycles specifically require cell cycle regulator cyclin D3. Cyclin D3 dose-dependently controls extent to which...