A5077415014- Single-cell and spatial transcriptomics
- SARS-CoV-2 and COVID-19 Research
- Cell Image Analysis Techniques
- interferon and immune responses
- Mosquito-borne diseases and control
- Plant Virus Research Studies
- AI in cancer detection
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Herpesvirus Infections and Treatments
- Bacteriophages and microbial interactions
- Immunotherapy and Immune Responses
- Malaria Research and Control
- Glioma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Bacterial biofilms and quorum sensing
- Bacterial Infections and Vaccines
- Immune cells in cancer
- Nutrition and Health in Aging
- T-cell and B-cell Immunology
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Evolution and Genetic Dynamics
- Radiomics and Machine Learning in Medical Imaging
- Oral microbiology and periodontitis research
The University of Texas Medical Branch at Galveston
2022-2025
Beth Israel Deaconess Medical Center
2023-2025
Research Complex at Harwell
2023
Rutherford Appleton Laboratory
2023
Broad Institute
2022-2023
Dana-Farber Cancer Institute
2021-2023
Science and Technology Facilities Council
2023
University of Pittsburgh
2020-2022
Harvard University
2022
Texas A&M Health Science Center
2021
Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal and adjacent normal tissues of 28 MMRp 34 MMRd individuals. Analysis 88 cell subsets their 204 associated gene expression programs revealed extensive transcriptional spatial remodeling across discover hubs...
Highly multiplexed protein imaging is emerging as a potent technique for analyzing distribution within cells and tissues in their native context. However, existing cell annotation methods utilizing high-plex spatial proteomics data are resource intensive necessitate iterative expert input, thereby constraining scalability practicality extensive datasets. We introduce MAPS (Machine learning Analysis of Proteomics Spatial biology), machine approach facilitating rapid precise type...
The intricate interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations intestinal tissue environment. Our ability study these events on systems level is significantly limited by situ approaches capable of generating simultaneous insights from both microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for probing across multiple spatial modalities. We demonstrate MicroCart investigating...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve after its emergence. Given importance in viral infection and vaccine development, mutations the Spike gene have been studied extensively; however, impact of outside are poorly understood. Here, we report that a triple deletion (ΔSGF or ΔLSG) nonstructural protein 6 (nsp6) independently acquired Alpha Omicron sublineages SARS-CoV-2 augments nsp6-mediated antagonism type-I interferon (IFN-I) signaling....
Genetic recombination is a tremendous source of intrahost diversity in viruses and critical for their ability to rapidly adapt new environments or fitness challenges. While are routinely characterized using high-throughput sequencing techniques, characterizing the genetic products next-generation data remains challenge. Viral events can be highly diverse variable nature, including simple duplications deletions, more complex such as copy/snap-back recombination, intervirus intersegment...
The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice primary human airway cultures to examine the fitness antigenic relationship In both cultures, exhibited order BA.5 ≥ BA.2 BA.2.12.1 > BA.1; no difference in body weight loss was observed different sublineage-infected mice. BA.1-, BA.2-, BA.2.12.1-, BA.5-infected developed distinguishable cross-neutralizations...
Liver injury after COVID-19 vaccination is very rare and shows clinical histomorphological similarities with autoimmune hepatitis (AIH). Little known about the pathophysiology of vaccine-induced liver (VILI) its relationship to AIH. Therefore, we compared VILI AIH.Formalin-fixed paraffin-embedded biopsy samples from patients (n = 6) an initial diagnosis AIH 9) were included. Both cohorts by evaluation, whole-transcriptome spatial transcriptome sequencing, multiplex immunofluorescence, immune...
Dengue, caused by the dengue virus (DENV), presents a significant public health challenge with limited effective treatments. NITD-688 is potent panserotype DENV inhibitor currently in Phase II clinical trials. However, its mechanism of action not fully understood. Here, we present molecular details how inhibits DENV. binds directly to nonstructural protein 4B (NS4B) nanomolar affinities across all four serotypes and specifically disrupts interaction between NS4B 3 (NS3) without significantly...
Abstract Checkpoint blockade-mediated immunotherapy is emerging as an effective treatment modality for multiple cancer types. However, cells frequently evade the immune system, compromising effectiveness of immunotherapy. It crucial to develop screening methods identify patients who would most benefit from these therapies because risk side effects and high cost treatment. Here we show that expression MHC class I transactivator ( CITA ), NLRC5 , important efficient responses anti-CTLA-4...
Nutrient adaptation is key in limiting environments for the promotion of microbial growth and survival. In systems, iron an essential component many cellular processes bioavailability varies greatly among different conditions. bacterium, Klebsiella pneumoniae, impact limitation known to alter transcriptional expression iron-acquisition pathways influence secretion iron-binding siderophores; however, a comprehensive view at protein-level remains be defined. Here, we apply mass...
This study employed human induced pluripotent stem cells (hiPSCs) to model the interaction of HSV-1 with NPCs, which reside in neurogenic niches CNS and play a fundamental role adult neurogenesis. Herein, we provide evidence that NPCs infected at an MOI as low 0.001, can establish latent state, suggesting (i) variant classical latency be established during earlier stages neuronal differentiation (ii) brain may constitute additional sites viral reactivation. Lytic infections impaired NPC...
The intricate and dynamic interactions between the host immune system its microbiome constituents undergo shifts in response to perturbations intestinal tissue environment. Our ability study these events on systems level is significantly limited by
Abstract Background The impact of noncancerous factors on the morbidity and mortality glioblastoma multiforme (GBM) has not been well studied. Using a large surgical cohort, we examined association between multiple clinical characteristics postoperative morbidities survival in patients with GBM. Materials Methods study included 404 consecutive GBM who underwent initial tumor resection at MD Anderson Cancer Center January 1, 2010, December 31, 2014. Data about characteristics, treatments,...
Mass spectrometry-based proteomics enables the unbiased and sensitive profiling of cellular proteomes extracellular environments. Recent technological bioinformatic advances permit identifying dual biological systems in a single experiment, supporting investigation infection from both host pathogen perspectives. At ocular surface, Pseudomonas aeruginosa is commonly associated with biofilm formation inflammation tissues, causing damage to eye. The interaction between P. immune system at site...
An attenuated SARS-CoV-2 virus with modified viral transcriptional regulatory sequences and deletion of open-reading frames 3, 6, 7 8 (∆3678) was previously reported to protect hamsters from infection transmission. Here we report that a single-dose intranasal vaccination ∆3678 protects K18-hACE2 mice wild-type or variant challenge. Compared infection, the induces equivalent higher levels lung systemic T cell, B IgA, IgG responses. The results suggest as an attractive mucosal vaccine...
Classic Hodgkin Lymphoma (cHL) is a tumor composed of rare malignant and Reed-Sternberg (HRS) cells nested within T-cell rich inflammatory immune infiltrate. cHL associated with Epstein-Barr Virus (EBV) in 25% cases. The specific contributions EBV to the pathogenesis remain largely unknown, part due technical barriers dissecting microenvironment (TME) high detail. Herein, we applied multiplexed ion beam imaging (MIBI) spatial pro-teomics on 6 EBV-positive 14 EBV-negative samples. We identify...
Highly multiplexed protein imaging is emerging as a potent technique for analyzing distribution within cells and tissues in their native context. However, existing cell annotation methods utilizing high-plex spatial proteomics data are resource intensive necessitate iterative expert input, thereby constraining scalability practicality extensive datasets. We introduce MAPS ( M achine learning A nalysis of P roteomics S patial biology), machine approach facilitating rapid precise type...
Recombination is an essential driver of virus evolution and adaption, giving rise to new chimeric viruses, structural variants, sub-genomic RNAs defective RNAs. Next-generation sequencing (NGS) samples, either from experimental or clinical settings, has revealed a complex distribution recombination events that contributes intrahost diversity. We others have previously developed alignment tools discover map these diverse in NGS data. However, there no standard for data visualization...
SUMMARY Distal Visceral Endoderm (DVE) cells show a stereotypic unidirectional migration essential for correct orientation of the anterior-posterior axis. They migrate within simple epithelium, (VE). It is unknown how DVE negotiate their way amongst surrounding VE cells, what determines bounds VE, and relative contributions different cell behaviours to this migration. To address these questions, we used lightsheet microscopy generate multi-embryo, singlecell resolution, longitudinal dataset...
Abstract Objective Knowledge about the impact of metabolic disturbances and parenteral nutrition (PN) characteristics on survival cancer patients receiving PN is limited. We aimed to assess association between clinical in colorectal-cancer support. Methods Our study included 572 consecutive who had received support 2008 2013. Patient characteristics, body mass index, weight, medical/surgical history, indication for PN, data were recorded. Associations analysed with important confounding...
The most prevalent arthropod-borne viruses, including the dengue are primarily transmitted by infected mosquitoes. However, dynamics of virus (DENV) infection and dissemination in human skin following Aedes aegypti probing remain poorly understood. We exposed explants to adult female Ae. mosquitoes their with DENV-2 intrathoracic injection. Skin inoculated a similar quantity bifurcated needle were used as controls. Quantitative situ imaging revealed that DENV replication was greatest...
The advent of spatial transcriptomics and proteomics have enabled profound insights into tissue organization to provide systems-level understanding diseases. Both technologies currently remain largely independent, emerging same slide multi-omics approaches are generally limited in plex, resolution, analytical approaches. We introduce IN-situ DEtailed Phenotyping To High-resolution (IN-DEPTH), a streamlined resource-effective approach compatible with various platforms. This iterative first...
Abstract Dengue, caused by the dengue virus (DENV), presents a significant public health challenge with limited effective treatments. NITD-688 is potent pan-serotype DENV inhibitor currently in Phase II clinical trials. However, its mechanism of action not fully understood. Here, we present molecular details how inhibits DENV. binds directly to nonstructural protein 4B (NS4B) nanomolar affinities across all four serotypes and specifically disrupts interaction between NS4B 3 (NS3) without...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with poor prognosis and treatment options. Technological challenges in dissecting the immune constituents of PDAC tumor microenvironment (TME) has limited our understanding complex mechanisms vivo, which may part explain lack novel therapeutics for this recalcitrant disease. Here, we performed spatial proteomics using multiplexed ion beam imaging (MIBI) approach to quantify 36 signatures tissues from cohort twelve...