A5055812174- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- HER2/EGFR in Cancer Research
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- CAR-T cell therapy research
- Erythrocyte Function and Pathophysiology
- Advanced Biosensing Techniques and Applications
- Immune Response and Inflammation
- Galectins and Cancer Biology
- Immune Cell Function and Interaction
- Viral Infections and Outbreaks Research
- Advanced Fluorescence Microscopy Techniques
- Sepsis Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Toxin Mechanisms and Immunotoxins
- Neonatal Health and Biochemistry
- Invertebrate Immune Response Mechanisms
- Lymphoma Diagnosis and Treatment
- Vector-borne infectious diseases
- Dermatological and COVID-19 studies
- Respiratory Support and Mechanisms
- Malaria Research and Control
- Cell Image Analysis Techniques
University of Pennsylvania
2012-2024
University of Pittsburgh
2016-2018
Red blood cells detect and bind cell-free nucleic acids, contributing to anemia immune cell activation during acute inflammation.
COVID-19, the disease caused by SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized respiratory failure, arrhythmias, thromboembolic complications, shock with high mortality. Autopsy preclinical evidence implicate aberrant complement activation in endothelial injury failure. Erythrocytes express receptors are capable of binding immune complexes; therefore, we investigated patients COVID-19 using erythrocytes as a tool diagnose activation. We discovered...
A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful cases have reported in which vaccinees developed virulent wild type YFV infection. This efficacy is presumed to be result both neutralizing antibodies robust T cell response. However, particular immune components required for protection against never evaluated. An understanding mechanisms that underlie...
Patients with metastatic HER2 breast cancer (MBC) often become resistant to HER 2 targeted therapy and recur. The Panacea trial suggested that MBC patients were more likely respond checkpoint if TIL present or tumor expressed PD-L1. We assessed whether type I polarized dendritic cells (DC1) could improve in a preclinical model of HER2+ cancer. TUBO bearing mice vaccinated either MHC class II peptide pulsed DC1 (class HER2-DC1) concurrent sequentially administration anti-PD-1 anti-PDL1....
BACKGROUND. The molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes outcomes unknown. Therefore, we profiled inflammation dynamics over first 7 days ARDS, associated biomarkers with mortality, persistent multiple organ dysfunction (MODS).
Whole-brain imaging is becoming a fundamental means of experimental insight; however, achieving subcellular resolution imagery in reasonable time window has not been possible. We describe the first application multicolor ribbon scanning confocal methods to collect high-resolution volume images chemically cleared brains. demonstrate that collects over ten times faster than conventional high speed systems but with equivalent spectral and spatial resolution. Further, using this technology, we...
Red blood cells (RBCs) express the nucleic acid-binding toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs other TLRs is unknown. Here we show that RNA sensor TLR7. TLR7 present on red cell membrane associated with RBC protein Band 3. In patients SARS-CoV2-associated sepsis, TLR7-Band 3 interactions in are increased when compared healthy controls. vitro, synthetic ssRNA from viruses. Thus, may serve as a previously unrecognized sink for exogenous RNA,...
We have developed a new approach to reduce the serum interference for ELISA. The purpose of this study is investigate if we can use optimized ELISA (MBB-ELISA) detect soluble HER2/neu (sHER2) in early stage primary breast cancer and monitor its change during treatments. collected sera preoperatively from 118 patients. Serum samples were also sequentially subset patients after adjuvant treatment. sHER2 these was measured by MBB-ELISA. Only 16.7 % tissue HER2 (tHER2) positive had significantly...
Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved induction IFN-α/β after virus infection and resultant upregulation antiviral IFN-stimulated genes (ISGs) through receptor complex signaling. However, other than examining effects genetic deletion or effector pathway components, little known regarding functionality these responses intact hosts...
Live attenuated viruses are historically among the most effective viral vaccines. Development of a safe vaccine requires virus to be less virulent, phenotype that is arrived by empirical evaluation often leaving mechanisms attenuation unknown. The yellow fever 17D live strain has been developed as delivery vector for heterologous antigens; however, remain elusive. successful and progress development vaccines (LAVs) related flaviviruses an understanding molecular leading attenuation. Using...
Forkhead box P3 (FOXP3) is a "master regulator" of regulatory T cells (Tregs), which are subset that can suppress the antigen-specific immune reaction and play important roles in host tolerance homeostasis. It well known FOXP3 forms complexes with several proteins be regulated by various post-translational modifications (PTMs) such as acetylation, phosphorylation, ubiquitination, methylation. As consequence, PTMs change stability its capability to regulate gene expression, eventually affect...
Recruitment of immune cells to tumor targeted by a therapeutic antibody can heighten the antitumor efficacy antibody. For example, p185(her2/neu)-targeting antibodies not only downregulate p185(her2/neu) kinase (ERBB2) but also trigger complement-dependent cytotoxicity (CDC) and antibody-dependent cellular (ADCC) through Fc region. Here, we describe generalized strategy improve cell recruitment cancer cells, using modified scFv call "Grababody" that binds target protein endogenous...
Over-expression of the HER2/neu receptor occurs in 20 to 30 percent breast tumors and is linked poorer prognosis. The expression status determines whether or not patient will receive trastuzumab-based treatment. In clinical practice, over-expression routinely identified using Immunohistochemistry (IHC) Fluorescence Situ Hybridization (FISH), both which are invasive approaches requiring tissue samples. Serum assays for Extra Cellular Domain (HER2 ECD) have been reported but use very limited...
Despite substantial clinical progress with targeted therapies, current antibody-based approaches have limited efficacy at controlling HER2/neu-positive breast cancers, especially in the absence of chemotherapies. Previously, we showed that combination IFNγ and anti-HER2/neu antibody synergistically reduces tumor growth an vivo implanted mammary model. Here, report a recombinant approach to produce scFv fusion protein using engineered effector domain (EED) scaffold. The new molecule induces...
Red blood cells (RBCs), traditionally recognized for their role in transporting oxygen, play a pivotal the body's immune response by expressing TLR9 and scavenging excess host cell-free DNA. DNA capture RBCs leads to accelerated RBC clearance triggers inflammation. Whether can also acquire microbial during infections is unknown. Murine vitro bacterial-DNA-induced macrophage activation was augmented WT but not Tlr9-deleted RBCs. In mouse model of polymicrobial sepsis, RBC-bound bacterial...
Abstract RBCs demonstrate immunomodulatory capabilities through the expression of nucleic acid sensors. However, little is known about bat RBCs, and no studies have examined immune function erythrocytes. In this study, we show that express acid–sensing TLRs TLR7 TLR9 bind ligands, ssRNA, CpG DNA. Collectively, these data suggest that, like human erythrocytes possess may be reservoirs for acids. These findings provide unique insight into immunity uncover potential mechanisms by which virulent...
<p>Supplementary Information PDF file - 77K, Additional information on the HER2 Domain 4 sequence, methods and figure legends for supplemental figures</p>
<p>Supplementary Figure S2 PDF file 861K, Confirmation of h4D5 and D4(508-577) interaction by immunoprecipitation</p>
<div>Abstract<p>Recruitment of immune cells to tumor targeted by a therapeutic antibody can heighten the antitumor efficacy antibody. For example, p185<i><sup>her2/neu</sup></i>-targeting antibodies not only downregulate p185<i><sup>her2/neu</sup></i> kinase (ERBB2) but also trigger complement-dependent cytotoxicity (CDC) and antibody-dependent cellular (ADCC) through Fc region. Here, we describe generalized strategy improve cell...
<p>Supplementary Figure S4 PDF file 583K, In vivo activity of h4D5 in the T6-17 model</p>
<p>Supplementary Figure S3 PDF file 1739K, Binding of antibodies to D4(508-577) by SPR analysis</p>
<div>Abstract<p>Recruitment of immune cells to tumor targeted by a therapeutic antibody can heighten the antitumor efficacy antibody. For example, p185<i><sup>her2/neu</sup></i>-targeting antibodies not only downregulate p185<i><sup>her2/neu</sup></i> kinase (ERBB2) but also trigger complement-dependent cytotoxicity (CDC) and antibody-dependent cellular (ADCC) through Fc region. Here, we describe generalized strategy improve cell...