A5012758116- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- Immune cells in cancer
- Cancer-related molecular mechanisms research
- Viral-associated cancers and disorders
- MicroRNA in disease regulation
- Pancreatic and Hepatic Oncology Research
- Gene expression and cancer classification
- Circular RNAs in diseases
- CAR-T cell therapy research
- Respiratory viral infections research
- Lymphoma Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Influenza Virus Research Studies
- Diabetes and associated disorders
- Acute Lymphoblastic Leukemia research
Siemens Healthcare (Germany)
2024
Stanford University
2013-2022
Notable Labs (United States)
2018-2021
Baxter (United States)
2011-2017
Stanford Medicine
2010-2017
Institute of Immunology
2010
Institut Pasteur
2005
University of Giessen
2001
The molecular basis of gammadelta T cell receptor (TCR) recognition is poorly understood. Here, we analyze the TCR sequences a natural population specific for major histocompatibility complex class Ib molecule T22. We find that T22 correlates strongly with somatically recombined TCRdelta complementarity-determining region 3 (CDR3) motif derived from germ line-encoded residues. Sequence diversity around these residues modulates ligand-binding affinities, whereas V gene usage mainly tissue...
Abstract In silico quantification of cell proportions from mixed-cell transcriptomics data (deconvolution) requires a reference expression matrix, called basis matrix. We hypothesize that matrices created using only healthy samples single microarray platform would introduce biological and technical biases in deconvolution. show presence such two existing matrices, IRIS LM22, irrespective deconvolution method. Here, we present immunoStates, matrix built 6160 with different disease states...
The prokaryotic type II CRISPR/Cas9 system has been adapted to perform targeted genome editing in cells and model organisms. Here, we describe gene deletion replacement human via the using two guide RNAs. effectively generated deletions of varied length, regardless transcriptional status target gene. It is notable that RNAs resulted formation correct junctions at high efficiency. Moreover, presence a homology repair donor, could precise replacement. Our results illustrate can be used...
Oncogenes, which are essential for tumor initiation, development, and maintenance, valuable targets cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL). controls strength threshold Notch in tumorigenesis part dampening...
Emerging evidence suggests that microRNAs (miRNAs), an abundant class of ∼22-nucleotide small regulatory RNAs, play key roles in controlling the post-transcriptional genetic programs stem and progenitor cells. Here we systematically examined miRNA expression profiles various adult tissue-specific cells their differentiated counterparts. These analyses revealed are common or unique to blood, muscle, neural cell populations signatures mark transitions from self-renewing quiescent proliferative...
Understanding the consequences of tuning TCR signaling on selection, peripheral T cell function, and tolerance in context native repertoires may provide insight into physiological control tolerance. In this study, we show that genetic ablation a natural tuner signaling, mir-181a-1/b-1, double-positive thymocytes dampened Erk increased threshold positive selection. Whereas mir-181a-1/b-1 deletion mice resulted an increase intrinsic reactivity naive cells to self-antigens, it did not cause...
Abstract Precision medicine approaches such as ex vivo drug sensitivity screening (DSS) are appealing to inform rational selection in myelodysplastic syndromes (MDSs) and acute myeloid leukemia, given their marked biologic heterogeneity. We evaluated a novel, fully automated DSS platform that uses high-throughput flow cytometry 54 patients with newly diagnosed or treatment-refractory neoplasms evaluate (blast cytotoxicity differentiation) 74 US Food Drug Administration–approved...
Transplant games are a way to promote organ donation and show case healthy transplant recipients. "The <i>AJT</i> Report" looks at this other major events for patients how they came be. Also issue, we review highlights of early data from OPTN/UNOS on the new kidney allocation system implemented in 2014.
Summary The expression of major histocompatibility complex class II (MHC II) molecules is post‐translationally regulated by endocytic protein turnover. Here, we identified the serine protease cathepsin G (CatG) as an MHC II‐degrading in vitro screening and examined its role turnover vivo . CatG, uniquely among proteases tested, initiated cleavage detergent‐solubilized native recombinant soluble molecules. CatG cleaved human leukocyte antigen (HLA)‐DR isolated from both HLA‐DM‐expressing...
Abstract In silico quantification of cell proportions from mixed-cell transcriptomics data (deconvolution) requires a reference expression matrix, called basis matrix. We hypothesized that matrices created using only healthy samples single microarray platform would introduce biological and technical biases in deconvolution. show presence such two existing matrices, IRIS LM22, irrespective the deconvolution method used. Here, we present immunoStates, matrix built 6160 with different disease...
Systems immunology has the potential to offer invaluable insights into development of immune system. Two recent studies an in-depth view both dynamics system and heritability levels key modulators at birth.
Abstract CMV infection is a significant complication after solid organ transplantation. We used single cell TCR αβ sequencing to determine how memory inflation impacts clonality and diversity of the CMV-responsive CD8 CD4 T repertoire in first year transplantation human subjects. observed but no changes clonal diversity, indicating homeostatic stability clones. In contrast, was diverse stable over time, with evidence expansion. identified shared CDR3 motifs among patients public CMV-specific...
Cytomegalovirus (CMV) infection is a known cause of morbidity and mortality in solid organ transplant recipients. While primary controlled by healthy immune system, CMV never eradicated due to viral latency periodic reactivation. Transplantation associated therapies hinder surveillance CMV. CD4 T cells are an important part control We therefore investigated how impacts differentiation, functionality, expansion protective from recipients heart or kidney the first year post-transplant without...