A5003621059- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Respiratory viral infections research
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- vaccines and immunoinformatics approaches
- Virus-based gene therapy research
- Diabetes and associated disorders
- Virology and Viral Diseases
- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- Poxvirus research and outbreaks
- interferon and immune responses
- Herpesvirus Infections and Treatments
- Pneumonia and Respiratory Infections
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Peptidase Inhibition and Analysis
- Intensive Care Unit Cognitive Disorders
- Polyomavirus and related diseases
Wake Forest University
2016-2025
The University of Texas Health Science Center at Houston
2024
Atrium Health Wake Forest Baptist
2019-2023
Wake Forest Baptist Comprehensive Cancer Center
2019-2023
Community Partners
2021
Stony Brook Medicine
2021
Bipar
2006
National Cancer Institute
1996-2001
National Institutes of Health
1996-2001
Eli Lilly (United States)
2001
The conventional approach to cytotoxic T-lymphocyte (CTL) induction uses maximal antigen concentration with the intent of eliciting more CTL. However, efficacy this has not been systematically explored regard quality CTLs elicited or their in vivo functionality. Here, we show that a diametrically opposite elicits are much effective at clearing virus. specific for defined peptide epitope were selectively expanded various concentrations antigen. generated exceedingly low-dose lysed targets...
Experimental data suggest that negative selection of thymocytes can occur as a result supraoptimal antigenic stimulation. It is unknown, however, whether such mechanisms are at work in mature CD8+ T lymphocytes. Here, we show effector cytotoxic lymphocytes (CTL) susceptible to proliferative inhibition by high dose peptide antigen, leading apoptotic death mediated TNF-alpha release. Such not reflected the cytolytic potential CTL, since concentrations antigen inhibitory for proliferation...
Abstract Previously, we observed that high-avidity CTL are much more effective in vivo than low-avidity elimination of infected cells, but the mechanisms behind their superior activity remained unclear. In this study, identify two complementary mechanisms: 1) lyse cells earlier course a viral infection by recognizing lower Ag densities those distinguished and 2) they initiate lysis target rapidly at any given density. Alternative were excluded, including: possibility might control virus time...
Spontaneous regression/complete resistance (SR/CR) mice resist very high doses of cancer cells that are lethal to WT even at low doses. In this study, we show is mediated by rapid infiltration leukocytes, mostly innate immunity, in both primary and repeated challenges. Formation rosettes with infiltrating natural killer cells, neutrophils, macrophages was required for the subsequent destruction through cytolysis. Highly purified macrophages, neutrophils from SR/CR independently killed vitro....
Tumor-infiltrating myeloid cells are the most abundant leukocyte population within tumors. Molecular cues from tumor microenvironment promote differentiation of immature toward an immunosuppressive phenotype. However, in situ dynamics transcriptional reprogramming underlying this process poorly understood. Therefore, we applied single cell RNA-seq (scRNA-seq) to computationally investigate cellular composition and adjacent normal tissues 4 early-stage non-small lung cancer (NSCLC) patients....
Immunotherapy with checkpoint inhibitors is improving the outcomes of several cancers. However, only a subset patients respond. Therefore, predictive biomarkers are critically needed to guide treatment decisions and develop approaches therapeutic resistance.We compared bioenergetics circulating immune cells metabolomic profiles plasma obtained at baseline from melanoma treated anti-PD-1 therapy. We also performed single-cell RNA sequencing (scRNAseq) correlate transcriptional changes...
Abstract The nature of alloreactivity to MHC molecules has been enigmatic, primarily because the observation that allogeneic responses are considerably stronger than syngeneic responses. To better determine specificity potential responses, we have generated alloreactive CTL specific for exogenous, viral-derived peptide ligands. This approach allowed us critically evaluate both peptide- and MHC-specificity these T cells. Exploiting accessibility H-2Ld class I molecule exogenous ligands, were...
Abstract Background Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular vaccine responses. Methods followed adults a retirement facility longitudinal clinical serological samples from the first Moderna mRNA-1273 dose starting February 2021 through their 3rd (booster) . Outcomes were titers, avidity, AIM+ T cell function phenotype. Statistical analysis used linear...
Objective— Fish oil, containing omega-3 fatty acids, attenuates atherosclerosis. We hypothesized that acid–enriched oils are atheroprotective through alteration of monocyte subsets and their trafficking into atherosclerotic lesions. Methods Results— Low–density lipoprotein receptor knockout apolipoprotein E −/− mice were fed diets 10% (calories) palm oil 0.2% cholesterol, supplemented with an additional echium (containing 18:4 n-3), or fish oil. Compared oil–fed low–density mice,...
KRAS is a key oncogenic driver in lung adenocarcinoma (LUAD). Chromatin-remodeling gene SMARCA4 comutated with LUAD; however, the impact of mutations on clinical outcome has not been adequately established. This study sought to shed light significance LUAD. The association survival outcomes was interrogated four independent cohorts totaling 564 patients: KRAS-mutant patients LUAD who received nonimmunotherapy treatment from (a) Cancer Genome Atlas (TCGA) and (b) MSK-IMPACT Clinical...
Estimating population prevalence and incidence of prior SARS-CoV-2 infection is essential to formulate public health recommendations concerning the COVID-19 pandemic. However, interpreting estimates based on sero-surveillance requires an understanding duration elevated antibodies following infection, especially in large number people with pauci-symptomatic or asymptomatic disease.We examined > 30,000 serology assays for specific IgG IgM acquired longitudinally 11,468 adults between April...
Background CD47 is an integral membrane protein that alters adaptive immunosurveillance when bound to the matricellular glycoprotein thrombospondin-1 (TSP1). We examined impact of CD47/TSP1 signaling axis on melanoma patient response anti-PD-1 therapy due alterations in T cell activation, proliferation, effector function, and bioenergetics. Methods A syngeneic B16 mouse model was performed determine if targeting as monotherapy or combination with impacted tumor burden. Cytotoxic (CD8+) cells...
We have established and studied a colony of mice with unique trait host resistance to both ascites solid cancers induced by transplantable cells. One dramatic manifestation this is age-dependent spontaneous regression advanced cancers. This powerful segregates as single-locus dominant trait, independent tumor burden, effective against cell lines from multiple types cancer. During or immediately after exposure, cancer cells provoke massive infiltration leukocytes, which form aggregates...
Cytotoxic T lymphocytes (CTLs) are primary mediators of viral clearance, but high burden can result in deletion antigen-specific CTLs. We previously reported a potential mechanism for this deletion: tumor necrosis factor (TNF)-alpha-mediated apoptosis resulting from stimulation with supraoptimal peptide-major histocompatibility complex. Here, we show that although death is mediated by TNF-alpha and its receptor (TNF-RII), surprisingly neither the antigen dose dependence production nor...
Abstract In our previous studies, CTL that were sensitive to low concentrations of peptide Ag found be far superior those requiring high for reducing viral burden when adoptively transferred into SCID mice. Thus it is important we understand the mechanisms control requirement with long-term goal selectively expanding these exquisitely cells in vivo. Although TCR affinity one parameter can affect sensitivity Ag, investigated whether additional may also involved. studies using a transgenic...
The expression of the HLA class I molecules on cell surface was investigated in hepatocellular carcinoma (HCC) lines using complement-mediated cytotoxicity (CMC) and flow cytometric analysis. Although HLA-A antigens were detected by CMC all tested, HLA-B -C not detectable six seven HCC lines. These results also confirmed analysis focusing HLA-Bw4 Bw6 public antigens. Furthermore, complementary DNA (cDNA) from each line tested for HLA-A, - B, transporter associated with antigen processing...
Abstract Infection with influenza A virus can lead to increased susceptibility subsequent bacterial infection, often Streptococcus pneumoniae. Given the substantial modification of lung environment that occurs following pathogen there is significant potential for modulation immune responses. In this study, we show infection mice virus, followed by noninvasive EF3030 strain pneumoniae, leads a decrease in virus-specific CD8+ T cell response lung. Adoptive-transfer studies suggest reduction...
The improved efficacy of high avidity CTL for clearance virus has been well-documented. Thus, elucidation the mechanisms that confer increased sensitivity to peptide ligand demonstrated by is critical. Using lines and low generated from a TCR transgenic mouse, we have found functional can be controlled expression CD8alphaalpha vs CD8alphabeta ability CTLs colocalize CD8 in membrane. Colocalization these molecules was mediated lipid rafts importantly, raft disruption resulted conversion into...
A large number of dendritic cell (DC) subsets have now been identified based on the expression a distinct array surface markers as well differences in functional capabilities. More recently, concept unique has extended to lung, although capabilities these are only beginning be explored. Of particular interest respiratory DCs that express CD103. These cells line airway and act sentinels for pathogens enter migrating draining lymph node, where they add already complex DC present at this site....
Abstract Influenza virus infection of neonates poses a major health concern, often resulting in severe disease and hospitalization. At present, vaccines for this at-risk population are lacking. Thus, development an effective vaccine is urgent need. In study, we have used innovative nonhuman primate neonate challenge model to test the efficacy novel TLR 7/8 agonist R848-conjugated influenza vaccine. The use intact represents step forward conjugate design because it provides multiple antigenic...