A5047433549- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Cardiovascular Disease and Adiposity
- Cancer Risks and Factors
- Respiratory viral infections research
- Biosimilars and Bioanalytical Methods
- Influenza Virus Research Studies
- Cancer, Lipids, and Metabolism
- Corporate Insolvency and Governance
- BRCA gene mutations in cancer
- Helminth infection and control
- Animal Disease Management and Epidemiology
- Chemokine receptors and signaling
- Mesenchymal stem cell research
- Congenital Anomalies and Fetal Surgery
- Franchising Strategies and Performance
- Child Nutrition and Water Access
- Eosinophilic Esophagitis
- Parasitic infections in humans and animals
- Parasites and Host Interactions
- Linguistics, Language Diversity, and Identity
- Dietary Effects on Health
Emory University
2019-2025
National Institutes of Health
2018-2021
National Institute of Allergy and Infectious Diseases
2018-2021
Pharmaceuticals and Medical Devices Agency
2018
Ministry of Food and Drug Safety
2018
Harvard University
2015-2018
Massachusetts General Hospital
2018
Resident memory T cells (TRM cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung TRM cell populations to protective immunity and factors that govern their localization different compartments not well understood. Here, we show airway interstitial have distinct effector functions CXCR6 controls partitioning within by recruiting CD8 airways. The absence significantly decreases due altered trafficking CXCR6−/− lung, decreased survival in...
Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance anti-VEGF include the up-regulation alternative angiogenic and proinflammatory factors. Obesity is associated hypoxic adipose tissues, including those breast, resulting increased production some aforementioned Hence, we hypothesized that obesity could contribute therapy's lack efficacy. We found BC harbored systemic concentrations...
CD8 T cells play an essential role in antitumor immunity and chronic viral infections. Recent findings have delineated the differentiation pathway of accordance with progenitor-progeny relationship TCF1 + stem-like Tim-3 − more differentiated cells. Here, we investigated characteristics isolated from several murine tumor models human lung cancer samples terms phenotypic transcriptional features as well their location compared to virus-specific chronically lymphocytic choriomeningitis virus...
Abstract Purpose: Combination of chemotherapy with programmed cell death 1 (PD-1) blockade is a front-line treatment for lung cancer. However, it remains unknown whether and how affects the response exhausted CD8 T cells to PD-1 blockade. Experimental Design: We used well-established mouse model T-cell exhaustion chronic lymphocytic choriomeningitis virus (LCMV) infection assess effect (cisplatin+pemetrexed) on blockade, in absence impact antigen release presentation observed tumor models....
Abstract Probing the limits of CD8+ T cell immunosurveillance, we inserted SIINFEKL peptide into influenza A virus (IAV)–negative strand gene segments. Although IAV genomic RNA is considered noncoding, there a conserved, relatively long open reading frame present in segment 8, encoding potential protein termed NEG8. The biosynthesis NEG8 from has yet to be demonstrated. failed detect expression IAV-infected mouse cells, surface Kb–SIINFEKL complexes are generated when genetically appended...
Abstract Virus specific PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells are essential for maintaining cell responses during chronic infection and also critical PD-1 directed immunotherapy. In this study we have used the mouse model of LCMV to examine when these virus generated course what is role antigen in program. We found that early (day 5) their This generation suggested fate commitment population was agnostic eventual outcome immune system prepares a priori potential infection. Indeed, an...
<p>(A) Number of total lymphocytes, CD8 and CD4 T cells in the spleen across treatment groups. (B-C) Frequency PD-1+ LCMV-specific lung. Data are pooled from 2-3 experiments 4-5 mice per group. For statistical analysis, one-way ANOVA test was used; numbers were Log10 transformed. Bars represent mean SEM. *p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001.</p>
Advances in genetic sequencing and other diagnostic technologies have enabled the use of precision medicine clinical cancer care, as well development novel therapies that are targeted to specific molecular drivers cancer. Developing these new agents making them accessible patients requires global studies regulatory review approval by different national agencies. Whereas trials present challenges for drug developers who conduct agencies oversee them, they also raise practical issues about...
<p>A) Number of total lymphocytes and CD8+ T cells in the spleen mice treated with either concomitant or sequential combination CT aPD-L1. (B) Representative FACS plots showing frequency stem-like (PD-1+TCF-1+TIM-3-), effector transitory (PD-1+CX3CR1+TIM-3+) terminally differentiated (PD-1+CD101+TIM-3+) Gp33+ CD8 across treatment groups, quantified numbers shown (C). Data are pooled from 2 independent experiments 4-6 per group. For statistical analysis T-test was used, were Log10...
<p>(A) Design of the acute LCMV infection experiment. (B) Number total CD8+ T cells, and activated (CD44high) naïve (CD44low) cells in spleen acutely infected mice after treatment two groups. (C) Representative FACS plots showing frequency Gp33+ Gp276+ CD8 across groups, quantified numbers are shown on right. Data representative one out 2 independent experiments 3-5 per group. For statistical analysis T-test was used; were Log10 transformed. Bars represent mean SEM. Ns,...
<p>A) Number of total lymphocytes and CD8+ T cells in the spleen mice treated with either concomitant or sequential combination CT aPD-L1. (B) Representative FACS plots showing frequency stem-like (PD-1+TCF-1+TIM-3-), effector transitory (PD-1+CX3CR1+TIM-3+) terminally differentiated (PD-1+CD101+TIM-3+) Gp33+ CD8 across treatment groups, quantified numbers shown (C). Data are pooled from 2 independent experiments 4-6 per group. For statistical analysis T-test was used, were Log10...
<p>(A-C) Relative frequency of stem-like (PD-1+TCF-1+TIM-3-) (A), transitory effector (PD-1+CX3CR1+TIM-3+) (B), and terminally differentiated (PD-1+CD101+TIM-3+) (C) Gp276+ Gp33+ CD8 T cells in the spleen across treatment groups. Data are pooled from 2-3 experiments 4-5 mice per group. For statistical analysis one-way ANOVA test was used. Bars represent mean SEM. Ns, non-significant; * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001.</p>
<p>(A-C) Relative frequency of stem-like (PD-1+TCF-1+TIM-3-) (A), transitory effector (PD-1+CX3CR1+TIM-3+) (B), and terminally differentiated (PD-1+CD101+TIM-3+) (C) Gp276+ Gp33+ CD8 T cells in the spleen across treatment groups. Data are pooled from 2-3 experiments 4-5 mice per group. For statistical analysis one-way ANOVA test was used. Bars represent mean SEM. Ns, non-significant; * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001.</p>
<p>(A) Design of the acute LCMV infection experiment. (B) Number total CD8+ T cells, and activated (CD44high) naïve (CD44low) cells in spleen acutely infected mice after treatment two groups. (C) Representative FACS plots showing frequency Gp33+ Gp276+ CD8 across groups, quantified numbers are shown on right. Data representative one out 2 independent experiments 3-5 per group. For statistical analysis T-test was used; were Log10 transformed. Bars represent mean SEM. Ns,...
<p>(A) Number of total lymphocytes, CD8 and CD4 T cells in the spleen across treatment groups. (B-C) Frequency PD-1+ LCMV-specific lung. Data are pooled from 2-3 experiments 4-5 mice per group. For statistical analysis, one-way ANOVA test was used; numbers were Log10 transformed. Bars represent mean SEM. *p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001.</p>
<div>AbstractPurpose:<p>Combination of chemotherapy with programmed cell death 1 (PD-1) blockade is a front-line treatment for lung cancer. However, it remains unknown whether and how affects the response exhausted CD8 T cells to PD-1 blockade.</p>Experimental Design:<p>We used well-established mouse model T-cell exhaustion chronic lymphocytic choriomeningitis virus (LCMV) infection assess effect (cisplatin+pemetrexed) on blockade, in absence impact antigen release...
<div>AbstractPurpose:<p>Combination of chemotherapy with programmed cell death 1 (PD-1) blockade is a front-line treatment for lung cancer. However, it remains unknown whether and how affects the response exhausted CD8 T cells to PD-1 blockade.</p>Experimental Design:<p>We used well-established mouse model T-cell exhaustion chronic lymphocytic choriomeningitis virus (LCMV) infection assess effect (cisplatin+pemetrexed) on blockade, in absence impact antigen release...
Abstract Despite intense interest in antiviral T cell priming, the routes of virion movement lymph nodes (LNs) are imperfectly understood. Current models fail to explain how virus-infected cells rapidly appear within LN interior after viral infection. To better understand trafficking LN, we determined and infected-cell locations pox- zika-virus administration. Surprisingly, many infected were adjacent conduits. Using confocal electron microscopy, clearly visualized virions Functionally, CD8+...
Abstract Background: Most breast cancer (BC) patients are overweight or obese at the time of diagnosis. Obesity is associated with increased risk, recurrence, and worse prognosis BC. It has been shown that obesity associates outcome in metastatic kidney colon treated bevacizumab. If how excess body weight contributes to failure anti-VEGF therapy BC unknown. Results: Here we found diet-induced promoted resistance two syngeneic mouse models. The effects on tumor growth metastasis, VEGF...
Abstract To probe the limits of CD8+ T cell immunosurveillance, we inserted model peptide SIINFEKL into influenza A virus (IAV) negative strand gene segments. Although IAV genomic RNA is widely considered as non-coding, there a conserved, relatively long open reading frame present in segment eight, encoding potential protein termed NEG8. The biosynthesis NEG8 from has yet to be demonstrated. While failed detect expression infected cells, surface K b -SIINFEKL complexes are generated when...