A5030109235- Immune cells in cancer
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cellular Mechanics and Interactions
- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Long-Term Effects of COVID-19
- Toxoplasma gondii Research Studies
- Force Microscopy Techniques and Applications
- SARS-CoV-2 and COVID-19 Research
- Cell Image Analysis Techniques
- Respiratory Support and Mechanisms
- Mechanical and Optical Resonators
- Respiratory viral infections research
- Cytomegalovirus and herpesvirus research
- Cancer Cells and Metastasis
- Inflammation biomarkers and pathways
- Immune responses and vaccinations
- Herpesvirus Infections and Treatments
- DNA Repair Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Bacterial Genetics and Biotechnology
The University of Texas MD Anderson Cancer Center
2023-2025
University of California, San Francisco
2019-2025
Parker Institute for Cancer Immunotherapy
2022-2024
New York University
2024
Stanford University
2016-2019
Stratford University
2016
Applied BioPhysics (United States)
2016
Massachusetts Institute of Technology
2010-2015
IIT@MIT
2012
National Cancer Institute
1996
Significance The extracellular matrix is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells within our tissues. One the key components collagen, matrices collagen exhibit remarkable mechanical properties. Their resistance deformation enhanced as increased over short timescales, behavior termed strain stiffening, yet they some characteristics viscous fluids at longer timescales. Strikingly, we show stiffening coupled with their...
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,...
Triggering of the T cell receptor (TCR) integrates both binding kinetics and mechanical forces. To understand contribution cytoskeleton to these forces, we triggered cells using a novel application atomic force microscopy (AFM). We presented antigenic stimulation AFM cantilever while simultaneously imaging with optical measuring forces on cantilever. respond forcefully antigen after calcium flux. All responses were abrogated upon treatment an F-actin inhibitor. When emulated cantilever, even...
Abstract The rapid spread of SARS‐CoV‐2 in 2019 and 2020 has resulted a worldwide pandemic characterized by severe pulmonary inflammation, effusions, respiratory compromise. result this is large increasing number patients requiring endotracheal intubation prolonged ventilator support. rise intubations coupled with ventilation requirements will certainly lead to an increase tracheostomy procedures the coming weeks months. Performing setting active SARS‐CoV‐2, when necessary, poses unique...
Abstract The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results comparative lower tract transcriptional profiling tracheal aspirate 52 critically ill patients with COVID-19 or etiologies, as well controls without ARDS. In contrast to a “cytokine storm,” observe reduced proinflammatory gene expression in when compared due causes. is characterized by...
ABSTRACT Toxoplasma gondii transmission between intermediate hosts is dependent on the ingestion of walled cysts formed during chronic phase infection. Immediately following consumption, parasite must ensure survival host by preventing adverse inflammatory responses and/or limiting its own replication. Since secreted effectors rhoptry 16 kinase (ROP16) and dense granule 15 (GRA15) activate JAK-STAT3/6 NF-κB signaling pathways, respectively, we explored whether a particular combination these...
A stiffer cytoskeleton limits the responsiveness of naïve T cells; a flexible enables easy activation effector cells.
Summary Pathways of mutagenesis are induced in microbes under adverse conditions controlled by stress responses. Control responses may accelerate evolution specifically when cells maladapted to their environments, i.e. stressed. Stress‐induced the Escherichia coli Lac assay occurs either ‘point’ mutation or gene amplification. Point is associated with DNA double‐strand‐break (DSB) repair and requires DinB error‐prone polymerase SOS DNA‐damage‐ RpoS general‐stress We report that RpoE...
We have identified a novel role for hyaluronan (HA), an extracellular matrix polymer, in governing the mechanical properties of inflamed tissues. recently reported that insulitis type 1 diabetes mice and humans is preceded by intraislet accumulation HA, highly hygroscopic polymer. Using double transgenic DO11.10 × RIPmOVA (DORmO) mouse model diabetes, we asked whether autoimmune was associated with changes stiffness islets. To measure islet stiffness, used atomic force microscopy (AFM)...
Abstract Dexamethasone is the standard of care for critically ill patients with COVID-19, but mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk single-cell RNA sequencing samples from lower respiratory tract blood, assess plasma cytokine profiling to study dexamethasone on both systemic pulmonary immune cell compartments. In blood samples, associated decreased expression genes T activation, including TNFSFR4...
In the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, epithelial populations in distal lung expressing Angiotensin-converting enzyme (ACE2) are infrequent, and therefore, model viral expansion immune cell engagement remains incompletely understood. Using human lungs to investigate early host-viral pathogenesis, we found that SARS-CoV-2 had a rapid specific tropism for myeloid populations. Human alveolar macrophages (AMs) reliably expressed ACE2...
Intratumoral heterogeneity (ITH)-defined as genetic and cellular diversity within a tumor-is linked to failure of immunotherapy an inferior anti-tumor immune response. We modeled heterogeneous tumors comprised "hot" "cold" tumor populations (giving rise T cell-rich cell-poor tumors, respectively) introduced fluorescent labels enable precise spatial tracking. found the cold cell population exerted "dominant cold" effect in mixed tumors. Strikingly, analysis revealed that cells themselves...
Abstract We isolated and characterized three genes, crcA, cspE crcB, which when present in high copy confer camphor resistance on a cell suppress mutations the chromosomal partition gene mukB. Both phenotypes require same genes. Unlike resistant mutants, number crcB do not result an increase ploidy of cells. The has been previously identified as cold shock-like protein with homologues all organisms tested. also demonstrate that causes nucleoids to decondense vivo genes are copy, chromosomes...
Abstract Multiphoton microscopy is a powerful technique for deep in vivo imaging scattering samples. However, it requires precise, sample-dependent increases excitation power with depth order to generate contrast tissue, while minimizing photobleaching and phototoxicity. We show here how adaptive can optimize illumination at each point 3D volume as function of the sample’s shape, without need specialized fluorescent labeling. Our method relies on training physics-based machine learning model...
Macrophages display flexible activation states that range between pro-inflammatory (classical activation) and anti-inflammatory (alternative activation). These macrophage polarization contribute to a variety of organismal phenotypes such as tissue remodeling susceptibility infectious inflammatory diseases. Several macrophage- or immune-related genes have been shown modulate disease pathogenesis. However, the potential role differences in play modulating is just emerging. We integrated...
Abstract Intratumoral heterogeneity (ITH)—defined as genetic and cellular diversity within a tumor—is linked to failure of immunotherapy an inferior anti-tumor immune response. The underlying mechanism this association is unknown. To address question, we modeled heterogeneous tumors comprised pro-inflammatory (“hot”) immunosuppressive (“cold”) tumor population, labeled with YFP RFP tags respectively enable precise spatial tracking. resulting mixed-population exhibited distinct regions +...