A5009565869- Acute Myeloid Leukemia Research
- Animal Genetics and Reproduction
- Effects of Radiation Exposure
- Acute Lymphoblastic Leukemia research
- Virus-based gene therapy research
- Cancer Research and Treatments
- Histone Deacetylase Inhibitors Research
- DNA Repair Mechanisms
- Reproductive System and Pregnancy
- Nuclear Receptors and Signaling
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Animal health and immunology
- MicroRNA in disease regulation
- Endometriosis Research and Treatment
- Circular RNAs in diseases
- Immune Response and Inflammation
- Synthesis and biological activity
- Radiation Therapy and Dosimetry
- Chronic Myeloid Leukemia Treatments
- Immunotherapy and Immune Responses
- Cancer therapeutics and mechanisms
- Immune Cell Function and Interaction
- Lung Cancer Treatments and Mutations
- Nitric Oxide and Endothelin Effects
Wake Forest University
2015-2024
National Cancer Institute
2006-2023
University of Maryland, College Park
2007-2023
Institut thématique Génétique, génomique et bioinformatique
2023
Atrium Health Wake Forest Baptist
2016-2019
University Medical Center
2016
Virginia–Maryland College of Veterinary Medicine
1998-2013
Virginia Tech
1998-2013
Center for Cancer Research
2008-2012
Center for Molecular Medicine and Immunology
2012
Endogenous costimulatory molecules on T cells such as 4-1BB (CD137) can be leveraged for cancer immunotherapy. Systemic administration of agonistic anti-4-1BB antibodies, although effective preclinically, has not advanced to phase 3 trials because they have been hampered by both dependency Fcγ receptor-mediated hyperclustering and hepatotoxicity. To overcome these issues, we engineered proteins simultaneously targeting a tumor stroma or antigen: FAP-4-1BBL (RG7826) CD19-4-1BBL. In the...
Background Recent reports have shown that microRNAs (miRNAs) regulate vital immunological processes and emerged as key regulators of immune system development function. Therefore, it is important to determine miRNA dysregulation its pathogenic contribution in autoimmune diseases, an aspect not adequately addressed thus far. Methodology/Principal Findings In this study, we profiled expressions splenic lymphocytes from three murine lupus models (MRL-lpr, B6-lpr NZB/WF1) with different genetic...
An important yet poorly understood facet of the life cycle a successful pathogen is host-to-host transmission. Hospital-acquired infections (HAI) resulting from transmission drug-resistant pathogens affect hundreds millions patients worldwide. Klebsiella pneumoniae, Gram-negative bacterium, notorious for causing HAI, with many these difficult to treat, as K. pneumoniae has become multidrug resistant. Epidemiological studies suggest that requires close contact and generally occurs through...
The role of the endogenous apelin system in pregnancy is not well understood. Apelin's actions are further complicated by expression multiple forms peptide. Using radioimmunoassay (RIA) alone, we established content chorionic villi preeclamptic (PRE) and normal pregnant women (NORM) at 36-38 wk gestation. Total was lower PRE compared with NORM (49.7±3.4 vs. 72.3±9.8 fmol/mg protein; n=20-22) associated a trend for preproapelin mRNA PRE. Further characterization isoforms HPLC-RIA conducted...
Heart disease is an increasingly recognized, serious late effect of radiation exposure, most notably among breast cancer and Hodgkin's survivors, as well the Hiroshima Nagasaki atomic bomb survivors. The purpose this study was to evaluate effects total-body irradiation (TBI) on cardiac morphology, function selected circulating biomarkers in a well-established nonhuman primate model. For we used male rhesus macaques that were exposed single dose ionizing gamma (6.5–8.4 Gy) 5.6–9.7 years...
Endometriosis is the growth of uterine lining (endometrium) outside uterus. In other chronic inflammatory diseases, mitochondrial dysfunction suspected playing a role in disease pathogenesis. However, little known about endometriosis function or its effects on tissue metabolism. The objectives this study were to analyze nonhuman primate (NHP) endometrium and identify metabolic features these tissues that may contribute disease.Mitochondrial was measured using respirometry analysis determine...
Fibrosis is a pathological process with few therapeutic options. Experimental molecules are being developed to counteract the fibrotic effects through TGFβ receptor inhibition. Additionally, phosphodiesterase 5 (PDE5) inhibitors also have anti-fibrotic effects; however, mechanism of action remains unresolved. IPW5371 an example experimental TGFβ-mediated compound, and tadalafil PDE5 inhibitor. Irradiation increases frequency lesions, driven by activation pathway. We hypothesized that...
Abstract To assess the role of CALM-AF10 fusion gene in leukemic transformation vivo, we generated transgenic mice that expressed a gene. Depending on line, at least 40% to 50% F1 generation developed acute leukemia median age 12 months. Leukemic typically had enlarged spleens, invasion parenchymal organs with malignant cells, and tumors myeloid markers such as myeloperoxidase, Mac1, Gr1. Although most leukemias were leukemia, many showed lymphoid features, CD3 staining, or clonal Tcrb Igh...
We sought to determine if a selective HDAC6 inhibitor (ACY-738) decreases disease in NZB/W mice. From 22 38weeks-of-age, mice were injected intraperitoneally with 5 or 20mg/kg of ACY-738, vehicle control. Body weight and proteinuria measured every 2weeks, while sera anti-dsDNA, Ig isotypes, cytokine levels 4weeks. Kidney was determined by evaluation sera, urine, immune complex deposition, renal pathology. Flow cytometric analysis assessed thymic, splenic, bone marrow, peripheral lymphocyte...
Administration of amplitude modulated 27·12 MHz radiofrequency electromagnetic fields (AM RF EMF) by means a spoon-shaped applicator placed on the patient's tongue is newly approved treatment for advanced hepatocellular carcinoma (HCC). The mechanism action tumour-specific AM EMF largely unknown.
To evaluate the potential use of zinc chelation for prostate cancer therapy using a new liposomal formulation chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN).TPEN was encapsulated in nontargeted liposomes or displaying an aptamer to target cells overexpression prostate-specific membrane antigen. The selectivity and therapeutic efficacy (targeted nontargeted) free TPEN were evaluated vitro tumor-bearing mice.TPEN chelates results reactive oxygen species imbalance leading...
Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes under hypoxic conditions, increasing rigidity, fragility, calcium influx-mediated dehydration, and adhesivity red blood cells. Increased fragility results in hemolysis, which reduces nitric oxide (NO) bioavailability, induces platelet activation inflammation leading to adhesion circulating Nitric Oxide inhibits activation. Nitrite has emerged as an attractive therapeutic agent targets delivery NO activity areas...
Our recent work has indicated that the DMP1 locus on 7q21, encoding a haplo-insufficient tumour suppressor, is hemizygously deleted at high frequency in breast cancer. The encodes DMP1α protein, an activator of p53 pathway leading to cell cycle arrest and senescence, two other functionally undefined isoforms, DMP1β DMP1γ. In this study, we show alternatively spliced ∼30% cancer cases with relatively decreased increased expression. RNA-seq analyses publicly available database showed...
Recent evidence supports a role for epigenetic alterations in the pathogenesis of systemic lupus erythematosus (SLE). MicroRNAs (miRNAs or miRs) are endogenous regulators whose expression is altered many diseases, including SLE. IL-6 an inflammatory cytokine produced by mesangial cells during nephritis (LN). contains potential binding site miRNA-let-7a (let-7a) its 3′ untranslated region (UTR). We found let-7a was significantly increased pre-diseased and actively diseased New Zealand...
Late-delayed radiation-induced brain injury (RIBI) is a major adverse effect of fractionated whole-brain irradiation (fWBI). Characterized by progressive cognitive dysfunction, and associated cerebrovascular white matter injury, RIBI deleteriously affects quality life for cancer patients. Despite extensive morphological characterization the pathogenesis unclear, thus limiting development effective therapeutics. We previously reported that with increased gene expression extracellular matrix...
To investigate intraocular penetration of orally administered doxycycline in the normal equine eye and to compare serum concentrations. Procedures Six mares were at 10 mg/kg every 12 h by nasogastric tube for 5 days. Blood, aqueous, vitreous samples collected on days 1 5. All assayed Aqueous also protein quantitation.Doxycycline was rapidly absorbed after first dose (T(max) value 1.42 +/- 1.28 h); elimination occurred slowly (median t(1/2) = 10.88 h). Doxycycline could not be detected...