A5050975906- Immunotherapy and Immune Responses
- Bladder and Urothelial Cancer Treatments
- CRISPR and Genetic Engineering
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Ovarian cancer diagnosis and treatment
- Advanced Drug Delivery Systems
- Receptor Mechanisms and Signaling
- Reproductive System and Pregnancy
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Disaster Response and Management
- Viral Infectious Diseases and Gene Expression in Insects
- Glycosylation and Glycoproteins Research
- Toxin Mechanisms and Immunotoxins
- Animal Genetics and Reproduction
- Proteoglycans and glycosaminoglycans research
- Growth Hormone and Insulin-like Growth Factors
Michigan United
2025
Neoleukin Therapeutics (United States)
2023-2024
Center for Biologics Evaluation and Research
2024
United States Food and Drug Administration
2024
Massachusetts Institute of Technology
2019-2023
University of Arkansas at Fayetteville
2014-2018
Marquette University
2018
University High School
2018
North Carolina State University
2016-2018
University of North Carolina at Chapel Hill
2016-2018
There is an urgent need to determine whether oversulfated chondroitin sulfate (OSCS), a compound contaminating heparin supplies worldwide, the cause of severe anaphylactoid reactions that have occurred after intravenous administration in United States and Germany.Heparin procured from Food Drug Administration, consisting suspect lots associated with clinical events as well control heparin, were screened blinded fashion both for presence OSCS any biologic activity could potentially link...
Heparan sulfate proteoglycans (HSPGs) play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment activation, as well promoting progression, metastasis, survival. M402 is rationally engineered, non-cytotoxic heparan (HS) mimetic, designed to inhibit multiple implicated tumor-host interactions, including VEGF, FGF2, SDF-1α, P-selectin, heparanase. A single s.c. dose of effectively...
Despite advances in immuno-oncology, the relationship between tumor genotypes and response to immunotherapy remains poorly understood, particularly high-grade serous tubo-ovarian carcinomas (HGSC). We developed a series of mouse models that carry human HGSCs grow syngeneic immunocompetent hosts address this gap. transformed murine-fallopian tube epithelial cells phenocopy homologous recombination-deficient tumors through combined loss Trp53, Brca1, Pten, Nf1 overexpression Myc Trp53 R172H,...
Nanoparticle surface chemistry is a fundamental engineering parameter that governs tumor-targeting activity. Electrostatic assembly generates controlled polyelectrolyte complexes through the process of adsorption and charge overcompensation utilizing synthetic polyions natural biomacromolecules; it can yield films with distinctive hydration, charge, presentation functional groups. Here, we used electrostatic layer-by-layer (LbL) to screen 10 different chemistries for their ability...
Humanitarian medical response to natural and human-made disasters can be complicated by high clinician, staff, patient turnover. While electronic records are being scaled up globally, their use remains limited in humanitarian settings. The Fast Electronic Medical Record (fEMR) system is an open-source health record specifically designed for resource-limited settings crises. was developed between 2010–2014 through iterative design process with multidisciplinary team members. It...
Although cytokine therapy is an attractive strategy to build a more robust immune response in tumors, cytokines have faced clinical failures due toxicity. In particular, interleukin-12 has shown great promise but was limited translation because of systemic this study, we demonstrate enhanced ability reduce toxicity without affecting the efficacy IL-12 therapy. We engineer material properties NP meet demands for optimal delivery by using layer-by-layer (LbL) approach. Importantly, LbL,...
Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering vaccine development. However, the immune response to chitosan not clearly understood due contradicting results literature regarding its immunoreactivity. Thus, this study, we analyzed effects of various biochemical properties, namely degree deacetylation (DDA), viscosity/polymer length endotoxin levels, on responses by antigen presenting cells (APCs). solutions from sources were treated with mouse...
Abstract Ovarian cancer is especially deadly, challenging to treat, and has proven refractory known immunotherapies. Cytokine therapy an attractive strategy drive a proinflammatory immune response in immunologically cold tumors such as many high grade ovarian cancers; however, this been limited the past due severe toxicity. We previously demonstrated use of layer‐by‐layer (LbL) nanoparticle (NP) delivery vehicle subcutaneous flank reduce toxicity interleukin‐12 (IL‐12) upon intratumoral...
Adoptive cell therapies (ACT) have shown reduced efficacy against solid tumor malignancies compared to hematologic malignancies, partly due the immunosuppressive nature of microenvironment (TME). ACT may be enhanced with pleiotropic cytokines that remodel TME; however, their expression needs tightly controlled avoid systemic toxicities. Here we show T cells can armored membrane-bound surface regulated using drug-responsive domains (DRDs) developed from 260-amino acid protein human carbonic...
Metastasis accounts for approximately 90% of breast cancer-related deaths. Therefore, novel approaches which prevent or control cancer metastases are significant clinical interest. Interleukin-12 (IL-12)-based immunotherapies have shown promise in controlling metastatic disease, yet modest responses and severe toxicities due to systemic administration IL-12 early trials hindered application. We hypothesized that localized delivery co-formulated with chitosan (chitosan/IL-12) could elicit...
Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and full-contact sports. Astrocyte cellular edema one of major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation aquaporin-4 (AQP4), a water channel protein, following injury. AZA antiepileptic drug has been shown inhibit AQP4 expression this study we investigate as therapeutic mitigate extent mTBI induced edema. We hypothesized mTBI-mediated...
Although metastasis is ultimately responsible for about 90% of breast cancer mortality, the vast majority breast-cancer-related deaths are due to progressive recurrences from non-metastatic disease. Current adjuvant therapies unable prevent a significant fraction patients with cancer. Autologous tumor cell vaccines (ATCVs) safe and potentially useful strategy recurrence, in personalized patient-specific manner, following standard-of-care resection. Given high intra-patient inter-patient...
There is a critical unmet clinical need for bladder cancer immunotherapies capable of inducing durable antitumor immunity. We have shown that four intravesical treatments with simple co-formulation interleukin-12 and the biopolymer chitosan not only destroy orthotopic tumors, but also promote potent long-lasting systemic immune response as evidenced through tumor-specific in vitro killing assays, complete protection from rechallenge, abscopal responses at distant non-treated tumors. This...
Abstract Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), modulate the functions of numerous cytokines. The aims this multidisciplinary research were to characterize binding interleukin-12 (IL-12) determine mechanism(s) by which influences IL-12 bioactivity. Heparin HS found bind human (hIL-12) with low micromolar affinity increase hIL-12 bioactivity more than 6-fold. Conversely, other GAGs did not demonstrate significant binding, nor their addition affect Biophysical...
Abstract Using Southern blot analysis of RT-PCR products, mRNA for three different somatostatin (SS) precursors (PSS-I, -II, and -III), which encode SS14, goldfish brain (gb)SS28, [Pro2]SS14, respectively, were detected in hypothalamus. PSS-I -II mRNA, but not PSS-III also cultured pituitary cells. We subsequently examined the effects mature peptides, gbSS28, on somatotrope signaling GH secretion. The gbSS28 was more potent than either SS14 or [Pro2]SS14 reducing basal release least...
The reverse hemolytic plaque assay (RHPA) was used in this study to further characterize the mechanism whereby low concentrations of dopamine (DA) stimulate PRL secretion vitro. Female Sprague-Dawley rats were as a source anterior pituitary cells for RHPA. Pituitary infused into Cunningham chambers along with suspension protein-A-coated ovine red blood cells. Excess rinsed from leaving monolayer attached glass. then incubated solutions containing antiserum (1:40) and various DA. After 4 h,...
ABSTRACT The HIV-1 Rev response element (RRE) is a 351-base in unspliced and partially spliced viral RNA; binding of the RRE by protein induces nuclear export RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), branched domain II) containing high-affinity Rev-binding site, two or three additional domains. We previously reported that assumes an “A” shape solution suggested location sites domains I II, opposite each other on legs A,...
Ailments of the bladder are often treated via intravesical delivery-direct application therapeutic into through a catheter. This technique is employed hundreds thousands times every year, but protocol development has largely been limited to empirical determination. Furthermore, numerical analyses delivery performed date have restricted static geometries and not accounted for deformation. study uses finite element analysis approach with biphasic solute transport investigate several parameters...
A novel reduced nicotinamide-dependent disulfide reductase, the 2,2'-dithiodiethanesulfonate [(S-CoM)2] reductase (CoMDSR) of Methanobacterium thermoautotrophicum was purified 405-fold to electrophoretic homogeneity. Both NADPH and NADH functioned as electron donors, although rates with were three times higher. Reduced factor F420, deazaflavin carrier characteristic methanogenic bacteria, not a substrate for enzyme. The enzyme most active (S-CoM)2 but could also reduce L-cystine at 23% rate....
Meeting abstracts Autologous tumor cell-based vaccines (ATCVs) have a number of potential advantages including multivalency and patient specificity. ATCVs contain many antigens, both known unknown which potentiate polyclonal responses capable responding to more diverse population