A5006580537- Cancer-related molecular mechanisms research
- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- T-cell and B-cell Immunology
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Response and Inflammation
- Mathematical Biology Tumor Growth
- RNA Research and Splicing
- IL-33, ST2, and ILC Pathways
- Chemokine receptors and signaling
- RNA regulation and disease
- Systemic Sclerosis and Related Diseases
- Cerebrospinal fluid and hydrocephalus
- Immune responses and vaccinations
- Epigenetics and DNA Methylation
- Respiratory viral infections research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Adipose Tissue and Metabolism
- MicroRNA in disease regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Systemic Lupus Erythematosus Research
Boston Children's Hospital
2025
Harvard University
2025
University of Pennsylvania
2016-2024
Stanford University
2013
The gut microbiota is a key environmental determinant of mammalian metabolism. Regulation white adipose tissue (WAT) by the process critical to maintaining metabolic fitness, and dysbiosis can contribute development obesity insulin resistance (IR). However, how regulates WAT function remains largely unknown. Here, we show that tryptophan-derived metabolites produced controlled expression miR-181 family in adipocytes mice regulate energy expenditure sensitivity. Moreover, dysregulation...
T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population cells, termed cTfh, have similarity to lymphoid Tfh, can provide help, and responded influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner they form long-lasting memory. Here, we identified a that expressed multiple activation markers could be readily by coexpression ICOS CD38. This subset more...
Primary graft dysfunction (PGD) is a principal cause of early morbidity and mortality after lung transplantation, but its pathogenic mechanisms are not fully clarified. To date, studies using standard clinical assays have linked microbial factors to PGD. We previously used comprehensive metagenomic methods characterize viruses in allografts >1 mo transplant found that levels Anellovirus, mainly torque teno (TTVs), were significantly higher than nontransplanted healthy controls. quantitative...
Immunotherapy in pancreatic ductal adenocarcinoma (PDA) remains a difficult clinical problem despite success other disease types with immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell therapy. Mechanisms driving immunosuppression poor infiltration PDA are incompletely understood. Here, we use genetically engineered mouse models of that recapitulate hallmarks human to demonstrate CD40 pathway activation is required for response radiotherapy ICB αCTLA-4 αPD-1. The...
Inflammatory cytokines are fundamental mediators of the organismal response to injury, infection, or other harmful stimuli. To elucidate early and mostly direct transcriptional signatures inflammatory cytokines, we profiled all immunologic cell types by RNAseq after systemic exposure IL1β, IL6, TNFα. Our results revealed a significant overlap in responses, with broad divergence between myeloid lymphoid cells, but very few cell-type-specific responses. Pathway motif analysis identified...
The transcriptional programs that regulate CD8 T-cell differentiation and function in the context of viral infections or tumor immune surveillance have been extensively studied; yet how long noncoding RNAs (lncRNAs) loci transcribe them contribute to regulation T cells during remains largely unexplored. Here, we report transcription lncRNA Morrbid is specifically induced by receptor (TCR) type I IFN stimulation early stages acute chronic lymphocytic choriomeningitis virus (LCMV) infection....
Diabetes mellitus (DM) is a risk factor for cancer. The role of DM-induced hyperglycemic (HG) stress in blood cancer poorly understood. Epidemiologic studies show that individuals with DM are more likely to have higher rate mutations genes found pre-leukemic hematopoietic stem and progenitor cells (pre-LHSPCs) including TET2. TET2-mutant pre-LHSPCs require additional hits evolve into full-blown leukemia and/or an aggressive myeloproliferative neoplasm (MPN). Intrinsic been shown cooperate...
Inhibition of anti-apoptotic proteins BCL-2 and MCL-1 to release pro-apoptotic protein BIM reactivate cell death could potentially be an efficient strategy for the treatment leukemia. Here, we show that a lncRNA, MORRBID, selective transcriptional repressor BIM, is overexpressed in human acute myeloid leukemia (AML), which associated with poor overall survival. In both animal models, MORRBID hyperactivation correlates two recurrent AML drivers, TET2 FLT3ITD. Mice individual mutations Tet2 or...
Abstract Mutations in PTPN11, which encodes the protein tyrosine phosphatase SHP2, contribute to ∼35% of cases juvenile myelomonocytic leukemia (JMML). A common clinical picture children with JMML is that it presents as a constitutive hyperinflammatory syndrome, partially reminiscent chronic adults. Thus, component associated state and abundant innate immune cells such neutrophils monocytes. Recently, we showed evolutionarily conserved mouse lncRNA Morrbid specifically expressed myeloid...
In systemic lupus erythematosus (lupus), environmental effects acting within a permissive genetic background lead to autoimmune dysregulation. Dysfunction of CD4+ T cells contributes pathology by providing help autoreactive B and cells, cell dysfunction coincides with altered DNA methylation histone modifications select gene loci. However, chromatin accessibility states distinct subsets mechanisms driving heterogeneous across patients remain poorly understood. We defined the transcriptome...
Abstract Neutrophils, eosinophils and “classical” monocytes collectively account for ~70% of blood leukocytes are among the shortest-lived cells in body. Precise regulation short lifespan these myeloid is critical to maintain effective host responses pathogens while minimizing deleterious consequences prolonged inflammation. However, how strictly controlled remains largely unknown. We identified a novel long non-coding RNA (lncRNA) that highly specifically expressed by neutrophils, response...
<p>Supplemental Methods: Mouse strains and flow cytometry antibodies Supplemental Figure 1: Individual tumor kinetics of the unirradiated in PDA model. Tumor (mean individual) irradiated survival B16-F10 melanoma 2: antibody depleted mice (Cd4, CD8 Ly6c) knockout (Morrbid, Batf3, IFN gamma, CD40.) Mean uMT B220 mice. 3: (IFNAR) (MyD88, TLR4, IFNAR, Sting.) 4: Flow plots for top RF variables effect RT 5: As figure 4, but CD40 6: supplemental peak response 7: Heat map that predict tumors...
<p>Supplemental Methods: Mouse strains and flow cytometry antibodies Supplemental Figure 1: Individual tumor kinetics of the unirradiated in PDA model. Tumor (mean individual) irradiated survival B16-F10 melanoma 2: antibody depleted mice (Cd4, CD8 Ly6c) knockout (Morrbid, Batf3, IFN gamma, CD40.) Mean uMT B220 mice. 3: (IFNAR) (MyD88, TLR4, IFNAR, Sting.) 4: Flow plots for top RF variables effect RT 5: As figure 4, but CD40 6: supplemental peak response 7: Heat map that predict tumors...
<div>Abstract<p>Immunotherapy in pancreatic ductal adenocarcinoma (PDA) remains a difficult clinical problem despite success other disease types with immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell therapy. Mechanisms driving immunosuppression poor infiltration PDA are incompletely understood. Here, we use genetically engineered mouse models of that recapitulate hallmarks human to demonstrate CD40 pathway activation is required for response radiotherapy ICB...
<div>Abstract<p>Immunotherapy in pancreatic ductal adenocarcinoma (PDA) remains a difficult clinical problem despite success other disease types with immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell therapy. Mechanisms driving immunosuppression poor infiltration PDA are incompletely understood. Here, we use genetically engineered mouse models of that recapitulate hallmarks human to demonstrate CD40 pathway activation is required for response radiotherapy ICB...