A5090951105- Cancer Immunotherapy and Biomarkers
- Esophageal Cancer Research and Treatment
- Immune cells in cancer
- RNA modifications and cancer
- Pancreatic and Hepatic Oncology Research
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Cardiac tumors and thrombi
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Ferroptosis and cancer prognosis
- Genomics and Phylogenetic Studies
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Translation Studies and Practices
- Congenital heart defects research
- RNA and protein synthesis mechanisms
University of Washington
2022-2024
University of California, San Francisco
2024
UCSF Helen Diller Family Comprehensive Cancer Center
2024
Mammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, single-cell zygote gives rise to millions of cells expressing panoply molecular programs. Although intensively studied, comprehensive delineation the major trajectories that comprise mammalian development in vivo remains elusive. Here, we set out integrate several RNA-sequencing (scRNA-seq) datasets collectively span mouse gastrulation organogenesis, supplemented with new...
Abstract The inability to scalably and precisely measure the activity of developmental cis -regulatory elements (CREs) in multicellular systems is a bottleneck genomics. Here we develop dual RNA cassette that decouples detection quantification tasks inherent multiplex single-cell reporter assays. resulting measurement expression accurate over multiple orders magnitude, with precision approaching limit set by Poisson counting noise. Together barcode stabilization via circularization, these...
Long-read DNA sequencing has recently emerged as a powerful tool for studying both genetic and epigenetic architectures at single-molecule single-nucleotide resolution. studies encompass the direct identification of native cytosine methylation well exogenously placed N6-methyladenine (DNA-m6A). However, detecting DNA-m6A modifications using sequencing, coprocessing architectures, is limited by computational demands lack supporting tools. Here, we introduce fibertools, state-of-the-art...
Abstract Long-read DNA sequencing has recently emerged as a powerful tool for studying both genetic and epigenetic architectures at single-molecule single-nucleotide resolution. studies encompass the direct identification of native cytosine methylation well exogenously placed N 6 -methyladenine (DNA-m6A). However, detecting DNA-m6A modifications using sequencing, co-processing architectures, is limited by computational demands lack supporting tools. Here, we introduce fibertools ,...
Abstract Sotigalimab is an agonistic anti-CD40 mAb that can modulate antitumor immune responses. In a phase II clinical trial of sotigalimab combined with neoadjuvant chemoradiation (CRT) in locally advanced esophageal/gastroesophageal junction (E/GEJ) cancer the primary outcome efficacy as measured by pathologic complete response (pCR) rate, combination induced pCR 38% treated patients. We investigated mechanism action samples obtained from this trial. Tumor biopsies and peripheral blood...
<p>Tumor-infiltrating myeloid cells are activated post-sotigalimab with alterations in antigen processing and metabolic pathways. <b>A,</b> MIBI analysis depicts changes cell density upregulation of activation markers for DCs the TME (representative image: patient 04). <b>B,</b> Quantification DC tumor pre- by total specific subset (pre <i>n</i> = 5, post 4). <b>C,</b> CD86, HLA-II, CD40 expression all post-treatment <b>D</b>...
<p>Treatment with sotigalimab increases immune infiltration into the TME, including T cells and myeloid cells. <b>A,</b> Patients were treated at initiation of study (a), beginning week 3 (b) 8 (c). Chemotherapy radiation initiated after second dose (b). Tissue biopsies blood samples collected timepoints pre-treatment, 3, surgery. Blood used to assess changes peripheral system using CyTOF (<a href="#bib1" target="_blank">1</a>) scRNAseq href="#bib3"...
<p>Sotigalimab results in immunomodulation and apoptosis of tumor cells. <b>A,</b> Tumor cells the TME were characterized using MIBI analysis keratin, HLA-I, HLA-II, PD-L1, CD40 (representative image: patient 04). <b>B,</b> Quantification cell density by (pre <i>n</i> = 5, post 4). <b>C–E,</b> Expression phenotypic markers was also quantified for HLA I II (C), PD-L1 (D), (E; pre <b>F–H,</b> Differential expression timepoint...
<p>Sotigalimab induces an activated T cell infiltrate and reduces Tregs in tumors. <b>A,</b> Characterization of subsets the TME was done by MIBI analysis using markers for DNA, keratin, CD4, CD8, CD45RO, Foxp3, Granzyme B (GZMB; representative image: patient 04). <b>B,</b> Percentage each are shown samples pre- post-treatment, out total intratumoral cells, as analyzed (pre <i>n</i> = 5, post 4). <b>C,</b> Ki67 expression all...
<p>Supplementary Figure 4</p>
<p>Supplementary Figure 2</p>
<p>Sotigalimab induces an activated T cell infiltrate and reduces Tregs in tumors. <b>A,</b> Characterization of subsets the TME was done by MIBI analysis using markers for DNA, keratin, CD4, CD8, CD45RO, Foxp3, Granzyme B (GZMB; representative image: patient 04). <b>B,</b> Percentage each are shown samples pre- post-treatment, out total intratumoral cells, as analyzed (pre <i>n</i> = 5, post 4). <b>C,</b> Ki67 expression all...
<p>Supplementary Figure 4</p>
<p>Sotigalimab induces activation and trafficking of immune cells within the blood. <b>A</b> <b>B,</b> Heat maps cell frequency surface marker expression as analyzed by CyTOF for T NK (A) antigen-presenting (B; pre <i>n</i> = 6, post 6). The count column shows number in each cluster. “frequency signif” columns indicates statistical significance differences which there were none. Red blue protein indicate significant up- or down-regulation indicated...
<p>Treatment with sotigalimab increases immune infiltration into the TME, including T cells and myeloid cells. <b>A,</b> Patients were treated at initiation of study (a), beginning week 3 (b) 8 (c). Chemotherapy radiation initiated after second dose (b). Tissue biopsies blood samples collected timepoints pre-treatment, 3, surgery. Blood used to assess changes peripheral system using CyTOF (<a href="#bib1" target="_blank">1</a>) scRNAseq href="#bib3"...
<p>Tumor-infiltrating myeloid cells are activated post-sotigalimab with alterations in antigen processing and metabolic pathways. <b>A,</b> MIBI analysis depicts changes cell density upregulation of activation markers for DCs the TME (representative image: patient 04). <b>B,</b> Quantification DC tumor pre- by total specific subset (pre <i>n</i> = 5, post 4). <b>C,</b> CD86, HLA-II, CD40 expression all post-treatment <b>D</b>...
<p>Sotigalimab induces activation and trafficking of immune cells within the blood. <b>A</b> <b>B,</b> Heat maps cell frequency surface marker expression as analyzed by CyTOF for T NK (A) antigen-presenting (B; pre <i>n</i> = 6, post 6). The count column shows number in each cluster. “frequency signif” columns indicates statistical significance differences which there were none. Red blue protein indicate significant up- or down-regulation indicated...
<p>Supplementary Figure 1</p>
<p>Supplementary Figure 2</p>
<p>Sotigalimab results in immunomodulation and apoptosis of tumor cells. <b>A,</b> Tumor cells the TME were characterized using MIBI analysis keratin, HLA-I, HLA-II, PD-L1, CD40 (representative image: patient 04). <b>B,</b> Quantification cell density by (pre <i>n</i> = 5, post 4). <b>C–E,</b> Expression phenotypic markers was also quantified for HLA I II (C), PD-L1 (D), (E; pre <b>F–H,</b> Differential expression timepoint...