A5080786053- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Immune cells in cancer
- 3D Printing in Biomedical Research
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- COVID-19 Clinical Research Studies
- Cellular Mechanics and Interactions
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Pancreatic and Hepatic Oncology Research
- Nanofabrication and Lithography Techniques
- Long-Term Effects of COVID-19
- Cancer Immunotherapy and Biomarkers
- Immune responses and vaccinations
- Enhanced Oil Recovery Techniques
- Microbial bioremediation and biosurfactants
- T-cell and B-cell Immunology
- Collagen: Extraction and Characterization
- Petroleum Processing and Analysis
- Wound Healing and Treatments
- Single-cell and spatial transcriptomics
- COVID-19 Impact on Reproduction
- Cell Image Analysis Techniques
University of California, San Francisco
2020-2024
University of Minnesota
2017-2021
Physical Sciences (United States)
2018-2021
Minneapolis Institute of Arts
2018
Indian Institute of Technology Kharagpur
2009
Abstract Directed migration by contact guidance is a poorly understood yet vital phenomenon, particularly for carcinoma cell invasion on aligned collagen fibres. We demonstrate that single cells, architectures providing cues induce constrained focal adhesion maturation and associated F-actin alignment, consequently orchestrating anisotropic traction stresses drive orientation directional migration. Consistent with this understanding, relaxing spatial constraints to either through reduction...
Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has pleiotropic and systemic effects in some individuals1-3, many others experience milder symptoms. Here, to gain a more comprehensive understanding of the distinction between mild phenotypes pathology disease 2019 (COVID-19) its origins, we performed whole-blood-preserving single-cell analysis protocol integrate contributions from all major immune cell types blood-including neutrophils, monocytes,...
Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here, in both murine human PDA, we demonstrate that extracellular matrix architecture regulates cell extrusion subsequent invasion from intact structures through tumor-associated collagen signatures (TACS). This results early dissemination histologically premalignant lesions continual well-differentiated disease, it suggests TACS as a biomarker to aid the pathologic assessment of Furthermore, show...
We present a novel platform to quantify spatiotemporal dynamics of cell behavior at and beyond the invasive front demonstrate that contact inhibition guidance orchestrate cancer invasion into anisotropic extracellular matrix.
CD206 is a common marker of putative immunosuppressive “M2” state in tumor-associated macrophages (TAMs). We made novel conditional (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs. Early depletion and monocytes (Mono/Macs) led the indirect loss conventional type I dendritic cells (cDC1), CD8 T cells, NK tumors. TAMs robustly expressed CXCL9, contrasting with stress-responsive Spp1-expressing immature monocytes, which became prominent early depletion. differentially...
Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway blood cells from patients with acute lung injury SARS-CoV-2 or other causes across 7 cohorts. This was associated greater clinical severity predicted future mechanical ventilation death.
Bispecific T-cell engager (BiTE) molecules are biologic T cell-directing immunotherapies. Blinatumomab is approved for treatment of B-cell malignancies, but BiTE molecule development in solid tumors has been more challenging. Here, we employed intravital imaging to characterize exposure and pharmacodynamic response an anti-muCD3/anti-huEGFRvIII mouse surrogate EGFR variant III (EGFRvIII)-positive breast implanted within immunocompetent mice. Our study revealed heterogeneous temporal spatial...
Abstract The anti-tumor function of CD8 T cells is limited through well-established pathways cell exhaustion (T EX ). Strategies to capture emergent functional states amongst this dominant trajectory dysfunction are necessary find durable immunity. By leveraging transcriptional reporting (by the fluorescent protein TFP) activation marker Cd69, related upstream AP-1 transcription factors, we define a classifier for potent versus sub-optimal CD69+ arising from stimulation. In tumors,...
Abstract Cell migration is strongly influenced by the organization of surrounding 3‐D extracellular matrix. In particular, within fibrous solid tumors, carcinoma cell invasion may be directed patterns aligned collagen in extra‐epithelial space. Thus, studying interactions heterogeneous populations cancer cells that include stem/progenitor‐like stem subpopulation and networks critical to our understanding dissemination. Here, we describe a robust method generate matrices vitro mimic vivo...
Tumor-associated macrophages (TAMs) are frequently categorized as being 'M1' or 'M2' polarized, even substantial data challenges this binary modeling of macrophage cell state. One molecule consistently referenced a delineator putative immunosuppressive state is the surface protein CD206. We thus made novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ 'M2-like' TAMs and assess their correspondence with pro-tumoral immunity. Early, but not late...
Abstract While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction COVID-19 pathology, its origins. performed wholeblood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes contents serum. Patients with mild disease display coordinated pattern interferonstimulated...
Abstract Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here in both murine human PDA we demonstrate that extracellular matrix architecture regulates cell extrusion subsequent invasion from intact structures through Tumor-Associated Collagen Signatures (TACS), resulting early dissemination histologically pre-malignant lesions continual well-differentiated Furthermore, show pancreatitis results invasion-conducive architectures, thus priming the stroma...
Summary T cell exhaustion is a major impediment to anti-tumor immunity. However, it remains elusive how other immune cells in the tumor microenvironment (TME) contribute this dysfunctional state. Here we show that biology of tumor-associated macrophages (TAM) and exhausted (T ex ) TME extensively linked. We demonstrate vivo depletion TAM reduces programs tumor-infiltrating CD8 + reinvigorates their effector potential. Reciprocally, transcriptional epigenetic profiling reveals express factors...
<h3>Background</h3> The idea that tumors co-opt elements of tissue repair and maintenance for growth immune evasion is a long-held one.<sup>1</sup> Cancer associated fibroblasts or CAFs can control the localization polarization state infiltrating cells, therefore they represent an enticing target clinical modulation.<sup>2–4</sup> Through mechanisms including ECM modulation, cytokine secretion even antigen presentation<sup>5</sup>, these relatively rare but powerful cells have potential to...
Abstract While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction COVID-19 pathology, its origins. performed whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes contents serum. Patients with mild disease display coordinated pattern interferon-stimulated...
Supplementary Data from Visualizing Spatial and Stoichiometric Barriers to Bispecific T-Cell Engager Efficacy
Supplementary Data from Visualizing Spatial and Stoichiometric Barriers to Bispecific T-Cell Engager Efficacy
Supplementary Data from Visualizing Spatial and Stoichiometric Barriers to Bispecific T-Cell Engager Efficacy
<div>Abstract<p>Bispecific T-cell engager (BiTE) molecules are biologic T cell–directing immunotherapies. Blinatumomab is approved for treatment of B-cell malignancies, but BiTE molecule development in solid tumors has been more challenging. Here, we employed intravital imaging to characterize exposure and pharmacodynamic response an anti-muCD3/anti-huEGFRvIII mouse surrogate EGFR variant III (EGFRvIII)-positive breast implanted within immunocompetent mice. Our study revealed...
Supplementary Data from Visualizing Spatial and Stoichiometric Barriers to Bispecific T-Cell Engager Efficacy