A5075263409- Extracellular vesicles in disease
- interferon and immune responses
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Inflammatory mediators and NSAID effects
- Cytokine Signaling Pathways and Interactions
- RNA regulation and disease
- Estrogen and related hormone effects
- Immunotherapy and Immune Responses
- S100 Proteins and Annexins
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- Immune Response and Inflammation
- Circular RNAs in diseases
- Bone Tissue Engineering Materials
- Ferroptosis and cancer prognosis
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Bacterial Infections and Vaccines
- Cancer Research and Treatments
- TGF-β signaling in diseases
- Pneumonia and Respiratory Infections
- Cancer Cells and Metastasis
- Pregnancy and preeclampsia studies
- Peptidase Inhibition and Analysis
Carnegie Mellon University
2016-2025
Mayo Clinic
2024
The Ohio State University
2019
University of Pittsburgh
2019
If I only had a heart 3D bioprinting is still fairly new technique that has been limited in terms of resolution and by the materials can be printed. Lee et al. describe printing to build complex collagen scaffolds for engineering biological tissues (see Perspective Dasgupta Black). Collagen gelation was controlled modulation pH could provide up 10-micrometer on printing. Cells embedded or pores introduced into scaffold via embedding gelatin spheres. The authors demonstrated successful five...
Purpose: The microenvironment of head and neck squamous cell carcinomas (HNSCC) is highly immunosuppressive. HNSCCs expressing elevated levels PD-L1 have especially poor outcome. Exosomes that carry suppress T-cell functions been isolated from plasma patients with HNSCC. potential contributions PD-L1+ exosomes to immune suppression disease activity are evaluated.Experimental Design: 40 HNSCC by size exclusion chromatography were captured on beads using anti-CD63 Abs, stained for PD-1...
Exosomes, small (30-150 nm) extracellular vesicles (EVs) isolated from plasma of patients with acute myeloid leukemia (AML) carry leukemia-associated antigens and multiple inhibitory molecules. Circulating exosomes can deliver suppressive cargos to immune recipient cells, inhibiting anti-tumor activities. Pre-therapy refractory/relapsed AML contains elevated levels immunosuppressive which interfere anti-leukemia functions activated cells. We show that pre-therapy the receiving adoptive NK-92...
For solid tumors, such as head and neck squamous cell carcinoma (HNSCC), an adequate blood supply is of critical importance for tumor development metastasis. Tumor-derived exosomes (TEX) accumulate in the microenvironment (TME) serve a communication system between normal stromal cells. This study evaluates vitro vivo effects mediated by TEX that result promotion angiogenesis. produced PCI-13 (HPV-) UMSCC47 (HPV+) lines or from plasma HNSCC patients were isolated mini size exclusion...
Systemic messenger RNA (mRNA) delivery to organs outside the liver, spleen, and lungs remains challenging. To overcome this issue, we hypothesized that altering nanoparticle chemistry administration routes may enable mRNA-induced protein expression of reticuloendothelial system. Here, describe a strategy for delivering mRNA potently specifically pancreas using lipid nanoparticles. Our results show nanoparticles containing cationic helper lipids by intraperitoneal produces robust specific in...
Photoinduced atom transfer radical polymerization (photo-ATRP) has risen to the forefront of modern polymer chemistry as a powerful tool giving access well-defined materials with complex architecture. However, most photo-ATRP systems can only generate radicals under biocidal UV light and are oxygen-sensitive, hindering their practical use in synthesis biohybrids. Herein, inspired by photoinduced electron transfer-reversible addition-fragmentation chain (PET-RAFT) polymerization, we...
Treating pregnancy-related disorders is exceptionally challenging because the threat of maternal and/or fetal toxicity discourages use existing medications and hinders new drug development. One potential solution lipid nanoparticle (LNP) RNA therapies, given their proven efficacy, tolerability, lack accumulation. Here, we describe LNPs for efficacious mRNA delivery to organs in pregnant mice via several routes administration. In placenta, our lead LNP transfected trophoblasts, endothelial...
Purpose: Exosomes, small extracellular vesicles (EVs) derived from the endocytic compartment of their parent cells, are present in plasma cancer patients and may serve as non-invasive biomarkers disease outcome. Here, we asked whether tumor-derived (TEX) and/or T-cell exosomes can predict outcome head neck squamous cell carcinoma (HNSCC) treated with oncological therapy.Materials Methods: 18 HNSCC enrolled phase I clinical trial receiving a combination cetuximab, ipilimumab radiation therapy...
The clinical translation of messengerRNA (mRNA) drugs has been slowed by a shortage delivery vehicles that potently and safely shuttle mRNA into target cells. Here, we describe the properties particularly potent branched-tail lipid nanoparticle delivers to >80% three major liver cell types. We characterize spatially, temporally, as function injection type. Following intravenous delivery, our induced greater protein expression than two benchmark lipids, C12-200 DLin-MC3-DMA, at an dose 0.5...
Exosomes show potential as ideal vehicles for drug delivery because of their natural role in transferring biological cargo between cells. However, current methods to engineer exosomes without negatively impacting function remain challenging. Manipulating exosome-secreting cells is complex and time-consuming, while direct functionalization exosome surface proteins suffers from low specificity efficiency. We demonstrate a rapid, versatile, scalable method with oligonucleotide tethers enable...
Exosomes are emerging as ideal drug delivery vehicles due to their biological origin and ability transfer cargo between cells. However, rapid clearance of exogenous exosomes from the circulation well aggregation shedding surface proteins during storage limit clinical translation. Here, we demonstrate highly controlled reversible functionalization exosome surfaces with well-defined polymers that modulate exosome’s physiochemical pharmacokinetic properties. Using cholesterol-modified DNA...
Interactions between tumor cells and tumor-associated macrophages (TAMs) are critical for glioblastoma progression. The TAMs represent up to 30% of the mass. role in progression mechanisms underlying growth remain unclear. Using an vitro model resembling crosstalk cells, we show that glioblastoma-derived exosomes (GBex) reprogram M1 (mediate pro-inflammatory function) M2 anti-inflammatory macrophages, converting into augmenting pro-tumor functions macrophages. In turn, these...
Therapeutic benefits of curcumin for inflammatory diseases have been demonstrated. However, curcumin's potential as a clinical therapeutic has hindered due to its low solubility and stability in vivo. We hypothesized that hybrid carrier incorporates albumin-binding extracellular vesicle (EV) encapsulation could effectively address the current challenges delivery. further postulated using dissolvable microneedle arrays (dMNAs) local delivery curcumin-albumin-EVs (CA-EVs) control skin...
Abstract The angiotensin II receptor AGTR1, which mediates vasoconstrictive and inflammatory signaling in vascular disease, is overexpressed aberrantly some breast cancers. In this study, we established the significance of an AGTR1-responsive NFκB pathway cancer subset. We documented that AGTR1 overexpression occurred luminal A B subtypes cancer, was mutually exclusive HER2 expression, correlated with aggressive features include increased lymph node metastasis, reduced responsiveness to...
Exosomes produced by tumor cells have been shown to reprogram functions of human immune cells. Molecular cargos exosomes isolated from supernatants HPV(+) and HPV(-) head neck cancer (HNC) cell lines or HNC patients' plasma were compared. The exosome protein profiles resembled those respective parent Only carried E6/E7, p16 survivin. negative for cyclin D1 low p53 levels. Immunomodulatory molecules (TGF-β, FasL, OX40, OX40L HSP70) exosomes. These co-incubated with T induced apoptosis...
Glioblastoma is one of the most immunosuppressive human tumors. Emerging data suggest that glioblastoma-derived exosomes (GBex) reprogram tumor microenvironment into a tumor-promoting milieu by mechanisms not yet understood.
Exosomes are 30–200 nm sized extracellular vesicles that increasingly recognized as potential drug delivery vehicles. However, exogenous exosomes rapidly cleared from the blood upon intravenous delivery, which limits their therapeutic potential. Here, we report bioactive exosome-tethered poly(ethylene oxide)-based hydrogels for localized of exosomes. Using cholesterol-modified DNA tethers, lipid membrane was functionalized with initiators to graft polymers in presence additional and...
Abstract Transforming growth factor β (TGFβ) is a major component of tumor‐derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ + TEX to promote tumor and pro‐tumor activities the microenvironment (TME) are largely unknown. produced head neck squamous cell carcinoma (HNSCC) lines carried angiogenesis‐promoting proteins. stimulated macrophage chemotaxis without notable M1/M2 phenotype shift reprogrammed primary human macrophages pro‐angiogenic...
Abstract Exosome secretion by cells is a complex, poorly understood process. Studies of exosomes would be facilitated method for increasing their production and release. Here, we present stimulating the exosomes. Cultured were treated or not with sodium iodoacetate (IAA; glycolysis inhibitor) plus 2,4-dinitrophenol (DNP; oxidative phosphorylation inhibitor). Exosomes isolated size-exclusion chromatography morphology, size, concentration, cargo components functional activity compared. IAA/DNP...
Extracellular vesicles (EVs) have recently garnered attention for their participation in host-microbe interactions pneumococcal infections. However, the effect of EVs on host immune system remain poorly understood. Our studies focus produced by Streptococcus pneumoniae (pEVs), and reveal that pEVs are internalized macrophages, T cells, epithelial cells. In vitro, induce NF-κB activation a dosage-dependent manner polarize human macrophages to an alternative (M2) phenotype. addition, pEV...
Extracellular vesicles (EVs) are characterized by complex cargo composition and carry a wide array of signalling cargo, including growth factors (GFs). Beyond surface-associated GFs, it is unclear if EV intralumenal biologically active. Here, bone morphogenetic protein-2 (BMP2), loaded directly into the lumen EVs designated engineered BMP2-EVs (eBMP2-EVs), was comprehensively its regulation osteoblastogenesis. eBMP2-EVs non-EV 'free' BMP2 were observed to similarly regulate Furthermore, cell...
Nanoscale extracellular vesicles (EVs) represent a unique cellular derivative that reflect the therapeutic potential of mesenchymal stem cells (MSCs) toward tissue engineering and injury repair without logistical safety concerns utilizing living cells. However, upon systemic administration in vivo,EVs undergo rapid clearance typically lack controlled targeted delivery, thus reducing their effectiveness regenerative therapies. Here, we describe strategy enables long-term vivo spatial EV...