A5091187053- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Systemic Sclerosis and Related Diseases
- Reproductive System and Pregnancy
- Radiopharmaceutical Chemistry and Applications
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- HIV/AIDS Research and Interventions
- T-cell and B-cell Immunology
- COVID-19 Clinical Research Studies
- Sarcoma Diagnosis and Treatment
- Long-Term Effects of COVID-19
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Extracellular vesicles in disease
- Gut microbiota and health
- Angiogenesis and VEGF in Cancer
- SARS-CoV-2 and COVID-19 Research
- Cancer, Stress, Anesthesia, and Immune Response
University of Pittsburgh
2016-2025
UPMC Hillman Cancer Center
2018-2025
University of Pittsburgh Medical Center
2021-2024
UPMC Health System
2022
Bucknell University
2012-2014
Pittsburg State University
2013
Western Pennsylvania Hospital
1963
Abstract Current immunotherapy paradigms aim to reinvigorate CD8 + T cells, but the contribution of humoral immunity antitumor remains understudied. Here, we demonstrate that in head and neck squamous cell carcinoma (HNSCC) caused by human papillomavirus infection (HPV ), patients have transcriptional signatures germinal center (GC) tumor infiltrating B cells (TIL-Bs) spatial organization immune consistent with tertiary lymphoid structures (TLS) GCs, both which correlate favorable outcome....
Significance A pool of latently infected resting CD4 + T cells in patients on antiretroviral therapy is a major barrier to cure for HIV-1. Clinical trials are underway assess whether small molecules can “kick” HIV-1 out latency, but the potency such latency reversing agents has not been evaluated at level single proviruses. Using unique quantitative system, we found that histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid), which being investigated clinically, did...
Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, immune cells within the tumor microenvironment (TME). To enable development of more efficacious therapies, we aim to study heterogeneity, signatures unique populations, cell-cell interactions non-immune populations in 6 human papillomavirus (HPV)+ 12 HPV- HNSCC patient matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset 134,606 cells, show...
There is an urgent need for improved understanding of the mechanisms and clinical characteristics acute respiratory distress syndrome (ARDS) due to coronavirus disease (COVID-19).
A chimeric antigen receptor-modified T-cell therapy recipient developed severe coronavirus disease 2019, intractable RNAemia, and viral replication lasting >2 months. Premortem endotracheal aspirate contained × 1010 acute respiratory syndrome 2 (SARS-CoV-2) RNA copies/mL infectious virus. Deep sequencing revealed multiple sequence variants consistent with intrahost virus evolution. SARS-CoV-2 humoral cell-mediated immunity were minimal. Prolonged transmission from immunosuppressed patients...
Significance Previously, we showed that the virus persists in human immunodeficiency (HIV)-infected individuals on antiretroviral therapy (ART) is derived from cells infected prior to initiating treatment. We also HIV-infected can undergo cellular proliferation during ART. However, it not known what fraction of persist ART are latent and actively producing HIV RNA. The method described here was developed determine produce RNA levels single cells, including have undergone proliferation....
A quantitative real-time PCR (qRT-PCR) assay with single-copy sensitivity targeting HIV-1 gag RNA (the [gSCA]) has been used widely to quantify plasma viremia below the limit of detection clinical assays in patients on effective antiretroviral therapy (ART), but viral 15 30% samples amplifies inefficiently because primer/probe mismatches. We sought develop improved increased by improving nucleic acid recovery, designing qRT-PCR primers and a probe for highly conserved region integrase pol...
ABSTRACT Although a number of PCR-based quantitative assays for measuring HIV-1 persistence during suppressive antiretroviral therapy (ART) have been reported, simple, sensitive, reproducible method is needed application to large clinical trials. We developed novel PCR cell-associated (CA) DNA and RNA, targeting highly conserved region in pol , with sensitivities 3 5 copies/1 million cells. evaluated the performance characteristics using peripheral blood mononuclear cells (PBMCs) from...
The recently developed droplet-based single-cell transcriptome sequencing (scRNA-seq) technology makes it feasible to perform a population-scale scRNA-seq study, in which the is measured for tens of thousands single cells from multiple individuals. Despite advances many clustering methods, there are few tailored methods studies. Here, we develop Bayesian mixture model (BAMM-SC) method cluster data individuals simultaneously. BAMM-SC takes raw count as input and accounts heterogeneity batch...
Abstract Immunotherapy targeting coinhibitory receptors has been highly successful in treating a wide variety of malignancies; however, only subset patients exhibits durable responses. The first FDA-approved immunotherapeutics PD1 and CTLA4, alone or combination, significantly improved survival but were also accompanied by substantial toxicity combination. third immune checkpoint inhibitor targets LAG3, receptor expressed on activated CD4+ CD8+ T cells, especially settings long-term...
Abstract Purpose: Ewing sarcoma and osteosarcoma are primary bone sarcomas occurring most commonly in adolescents. Metastatic relapsed disease associated with dismal prognosis. Although effective for some soft tissue sarcomas, current immunotherapeutic approaches the treatment of have been largely ineffective, necessitating a deeper understanding immunobiology. Experimental Design: Multiplex immunofluorescence analysis immune infiltration versus was conducted. To better understand states...
Abstract CD8 + T cells are critical mediators of antitumor immunity but differentiate into a dysfunctional state, known as cell exhaustion, after persistent receptor stimulation in the tumor microenvironment (TME). Exhausted (T ex ) characterized by upregulation coinhibitory molecules and reduced polyfunctionality. TME experience an immunosuppressive metabolic environment via levels nutrients oxygen buildup lactic acid. Here we show that terminally uniquely upregulate Slc16a11 , which...
Mechanisms of resistance to cancer immunotherapy remain poorly understood. Lymphocyte activation gene-3 (LAG3) signaling is regulated by a disintegrin and metalloprotease domain-containing protein-10 (ADAM10)- ADAM17-mediated cell surface shedding. Here, we show that mice expressing metalloprotease-resistant, noncleavable LAG3 mutant (LAG3
Tumor antigen-specific CD8+ T cells play a critical role in antitumor immunity. Clinical trials reinvigorating the immune system via checkpoint blockade (ICB) have shown remarkable clinical promise. Numerous studies identified an association between NKG7 expression and patient outcome across different malignancies. However, aside from these correlative observations, very little is known about its Herein, we utilized single-cell RNA sequencing (scRNA-seq) datasets, NKG7-deficient mice,...
A cure of HIV-1 has been achieved in one individual through allogeneic stem cell transplantation with a CCR5[INCREMENT]32 homozygous donor. Whether myeloablation and autologous for lymphoma patients on suppressive antiretroviral therapy can eliminate reservoirs is unknown. Low-level plasma viremia total DNA 2-LTR circles blood mononuclear cells were quantified after 10 using quantitative polymerase chain reaction assays capable single-copy nucleic acid detection. Plasma was detectable 9...
Objective. The goal of this study was to define viral kinetics after initiation raltegravir (RAL)–based antiretroviral therapy (ART). Methods. ART-naive patients received RAL, tenofovir disoproxil fumarate, and emtricitabine for 72 weeks. Human immunodeficiency virus type 1 (HIV-1) RNA were measured by ultrasensitive single-copy assays, first (d1)–, second (d2)–, and, third (d3)–phase decay rates estimated mixed-effects models. Decay data compared historical estimates efavirenz (EFV)–...
In "healthy" tumor cells, phosphatidylserine (PS) is predominately localized in the inner plasma membrane leaflet. During apoptosis, PS relocates to outer Herein, we established PSout models with cells lacking flippase component CDC50A, constantly exposing but alive. tumors developed bigger than wild-type (WT) tumors, featuring M2 polarized tumor-associated macrophages (TAMs) and fewer tumor-antigen-specific T cells. The receptor TIM-3 responsible for recognition. Employing an opposite...
Human regulatory T cells (T