A5022523634- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Malaria Research and Control
- CAR-T cell therapy research
- Immune cells in cancer
- Antimicrobial Resistance in Staphylococcus
- Vitamin D Research Studies
- Galectins and Cancer Biology
- Acute Myeloid Leukemia Research
- Immunotherapy and Immune Responses
- Aquaculture disease management and microbiota
- Reproductive System and Pregnancy
- Chronic Obstructive Pulmonary Disease (COPD) Research
- NF-κB Signaling Pathways
- Invertebrate Immune Response Mechanisms
- Hematopoietic Stem Cell Transplantation
- Chromosomal and Genetic Variations
- Adipose Tissue and Metabolism
- Pleural and Pulmonary Diseases
- Asthma and respiratory diseases
- Advanced Biosensing Techniques and Applications
- Bacterial biofilms and quorum sensing
- Amoebic Infections and Treatments
Massachusetts Institute of Technology
2013-2025
Integrated BioTherapeutics (United States)
2022-2023
University of California San Francisco Medical Center
2022
Stanford University
2022
Allen Institute
2019
Koch Institute for Integrative Cancer Research At MIT
2019
Nanyang Technological University
2007-2016
Centre National de la Recherche Scientifique
2008
Institute of Microbiology
2006
Hubei University
2003-2005
Abstract Macrophages are plastic and, in response to different local stimuli, can polarize toward multi-dimensional spectrum of phenotypes, including the pro-inflammatory M1-like and anti-inflammatory M2-like states. Using a high-throughput phenotypic screen library ~4000 FDA-approved drugs, bioactive compounds natural products, we find ~300 that potently activate primary human macrophages either or state, which ~30 capable reprogramming state another ~20 for reverse repolarization....
Background. Responses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell–based therapy is a promising modality treat post-HCT relapse.
Acute myeloid leukemia (AML) remains a therapeutic challenge, and paucity of tumor-specific targets has significantly hampered the development effective immune-based therapies. Recent paradigm-changing studies have shown that natural killer (NK) cells exhibit innate memory upon brief activation with IL-12 IL-18, leading to cytokine-induced memory-like (CIML) NK cell differentiation. CIML enhanced antitumor activity promising results in early phase clinical trials patients relapsed/refractory...
Plasmodium vivax causes over 100 million clinical infections each year. Primarily because of the lack a suitable culture system, our understanding biology this parasite lags significantly behind that more deadly species P. falciparum . Here, we present complete transcriptional profile throughout 48-h intraerythrocytic cycle three distinct isolates. This approach identifies strain specific patterns expression for subsets genes predicted to encode proteins associated with virulence and host...
Abstract Kupffer cells are liver resident macrophages and play critical role in fatty disease, yet the underlying mechanisms remain unclear. Here, we show that activation of G-protein coupled receptor 3 (GPR3) stimulates glycolysis protects mice from obesity disease. GPR3 induces a rapid increase via formation complexes between β-arrestin2 key glycolytic enzymes as well sustained through transcription genes. In mice, results enhanced glycolysis, reduced inflammation inhibition high-fat diet...
Despite advances in identifying the key immunoregulatory roles of many human leukocyte immunoglobulin-like receptor (LILR) family members, function inhibitory molecule LILRB3 (ILT5, CD85a, LIR3) remains unclear. Studies indicate a predominant myeloid expression; however, high homology within LILR and relative paucity reagents have hindered progress toward this receptor. To investigate its potential immunomodulatory capacity, panel LILRB3-specific monoclonal antibodies (mAbs) was generated....
Abstract ATP synthesis and thermogenesis are two critical outputs of mitochondrial respiration. How these regulated to balance the cellular requirement for energy heat is largely unknown. Here we show that major facilitator superfamily domain containing 7C (MFSD7C) uncouples respiration switch in response heme. When heme levels low, MSFD7C promotes by interacting with components electron transport chain (ETC) complexes III, IV, V, destabilizing sarcoendoplasmic reticulum Ca 2+ -ATPase 2b...
Antibiotic resistance critically limits treatment options for infection caused by opportunistic pathogens such as enterococci. Here, we investigate the antibiotic and immunological activity of anticancer agent mitoxantrone (MTX) in vitro vivo against vancomycin-resistant Enterococcus faecalis (VRE). We show that, vitro, MTX is a potent Gram-positive bacteria through induction reactive oxygen species DNA damage. also synergizes with vancomycin VRE, rendering resistant strains more permeable...
Microglia shift toward an inflammatory phenotype during aging that is thought to exacerbate age-related neurodegeneration. The molecular and cellular signals resolve neuroinflammation post-injury are largely undefined. Here, we exploit systems genetics methods based on the extended BXD murine reference family identify IGFBPL1 as upstream cis-regulator of microglia-specific genes switch off inflammation. expressed by mouse human microglia, higher levels its expression...
Abstract Club cells are known to function as regional progenitor repair the bronchiolar epithelium in response lung damage. By lineage tracing mice, we have shown recently that club also give rise alveolar type 2 (AT2s) and 1 (AT1s) during of damaged epithelium. Here, show when highly purified, anatomically phenotypically confirmed seeded 3-dimensional culture either bulk or individually, they proliferate differentiate into both AT2- AT1-like form alveolar-like structures. This...
BackgroundChronic obstructive pulmonary disease (COPD) is characterized by emphysema and/or bronchiolitis. Deficiency in vitamin D3 (VD3), which regulates gene expression through binding to D receptor (VDR), associated with high risks of COPD susceptibility. Alveolar macrophages (AM), are generated during early ontogeny and maintained alveoli self-renewal response cytokine GM-CSF, positively correlated severity emphysema. However, whether how VD3, VDR AM interact contribute pathogenesis at...
The design of long oligonucleotides for spotted DNA microarrays requires detailed attention to ensure their optimal performance in the hybridization process. main challenge is select an oligonucleotide element that represents each genetic locus/gene genome and unique, devoid internal structures repetitive sequences its Tm uniform with all other elements on microarray. Currently, publicly available programs microarray selection utilize various combinations cutoffs which parameter (uniqueness,...
Abstract Therapy-resistant microenvironments represent a major barrier toward effective elimination of disseminated cancer. Many hematologic and solid tumors are resistant to therapeutic antibodies in the bone marrow (BM), but not periphery (e.g., spleen). We previously showed that cyclophosphamide (CTX) sensitizes BM niche antibody therapeutics. Here, we show (i) resistance was induced only by tumor also intrinsic microenvironment; (ii) CTX treatment overcame both extrinsic mechanisms...
Host-acting compounds are emerging as potential alternatives to combating antibiotic resistance. Here, we show that bosutinib, an FDA-approved chemotherapeutic for treating chronic myelogenous leukemia, does not possess any activity but enhances macrophage responses bacterial infection. In vitro, bosutinib stimulates murine and human macrophages kill bacteria more effectively. a wound infection with vancomycin-resistant Enterococcus faecalis, single intraperitoneal injection or multiple...
Summary Macrophage activation is critical for the innate immune response, and its suppression by pathogens represents a significant barrier to clearance. Here we identify E. faecalis -derived lactic acid as key factor in suppressing macrophage via extracellular acidification. We demonstrate that mutants lacking lactate dehydrogenase ( ldh ), essential production pH reduction, fail suppress NF-κB. Mechanistically, faecalis- derived acts MCT-1 GPR81, impair ERK STAT3 phosphorylation, leading...
The emergence of multi-drug-resistant strains Plasmodium parasites has prompted the search for alternative therapeutic strategies combating malaria. One possible strategy is to exploit existing drugs as lead compounds. FK506 currently used in clinic preventing transplant rejection. It binds a α/β protein module approximately 120 amino acids known binding domain (FKBD), which found various organisms, including human, yeast, and falciparum (PfFKBD). Antiparasitic effects its analogues devoid...
Abstract Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural change phenotype, transcription function following treatment patients with pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic the effusions up-regulated markers characteristic M2 such as CD163 CD206. Differential expression...
Malignant ascites is a common clinical problem in ovarian cancer. NK cells are present the ascites, but their antitumor activity inhibited. The underlying mechanisms of inhibition have yet to be fully elucidated. Using an Fcγ receptor-mediated cell activation assay, we show that from cancer patients potently inhibits activation. Part inhibitory mediated by CA125, mucin 16 fragment shed tumors. Moreover, transcriptional analyses RNA sequencing reveal upregulation genes involved multiple...
In recent years a number of genome sequences for different plasmodium species have become available. This has allowed the identification numerous conserved genes across and significantly enhanced our understanding parasite biology. contrast little is known about specific differences between genomes partly due to lower sequence coverage therefore relatively poor annotation some draft particularly rodent malarias species.To improve current gene status P. berghei, chabaudi yoelii, we performed...
Abstract Development of targeted cancer therapy requires a thorough understanding mechanisms tumorigenesis as well action therapeutics. This is challenging because by the time patients are diagnosed with cancer, early events have already taken place. Similarly, development immunotherapies hampered lack appropriate small animal models autologous human tumor and immune system. In this article, we report mouse model acute myeloid leukemia (AML) system for studying leukemogenesis testing...