A5040201451- Cancer-related gene regulation
- Animal Disease Management and Epidemiology
- Kruppel-like factors research
- Virus-based gene therapy research
- Carcinogens and Genotoxicity Assessment
- Animal testing and alternatives
- Immunotoxicology and immune responses
- Vector-Borne Animal Diseases
- Nerve injury and regeneration
- Viral Infections and Vectors
- Peroxisome Proliferator-Activated Receptors
- MicroRNA in disease regulation
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- T-cell and Retrovirus Studies
- Herpesvirus Infections and Treatments
- Ginkgo biloba and Cashew Applications
- Veterinary Oncology Research
- Molecular Biology Techniques and Applications
- Genomics, phytochemicals, and oxidative stress
- Genetic Syndromes and Imprinting
- Lung Cancer Research Studies
- Dermatological diseases and infestations
- Glaucoma and retinal disorders
Pfizer (United States)
2021-2024
Experimental Pathology Laboratories
2016-2024
National Institute of Environmental Health Sciences
2016-2024
Triangle
2016-2021
Research Triangle Park Foundation
2017-2021
Drug Safety Research Unit
2021
University of Minnesota
2012-2018
University of Minnesota Medical Center
2014-2016
Twin Cities Orthopedics
2013
Sylvana Research
2013
Abstract Aging is the single most common risk factor for cancer. Peripheral and marrow-derived stem cells are long lived candidate cancer-initiating cell. Repeated rounds of replication likely required accumulation necessary genetic mutations. Based on facts that mesenchymal (MSC) transform with higher frequency than other cell types, tumors in aged C57BL/6 mice frequently fibrosarcomas, we used a genetically tagged bone marrow (BM) transplant model to show develop MSC-derived fibrosarcomas....
Friedreich's ataxia is a rare disorder resulting from deficiency of frataxin, mitochondrial protein implicated in the synthesis iron-sulfur clusters. Preclinical studies mice have shown that gene therapy promising approach to treat individuals with ataxia. However, recent report provided evidence AAVrh10-mediated overexpression frataxin could lead cardiotoxicity associated dysfunction. While evaluating an AAV9-based using chicken β-actin promoter, we showed toxic be reached mouse liver and...
ARF encodes a potent tumor suppressor that antagonizes MDM2, negative regulator of p53. also suppresses the proliferation cells lacking p53, and loss in p53-null mice, compared with or p53 singly null results broadened spectrum decreased latency. To investigate mechanism p53-independent suppression by ARF, potential interacting proteins were identified yeast two-hybrid screen. The antiapoptotic transcriptional corepressor C-terminal binding protein 2 (CtBP2) was identified, interactions both...
The CtBP transcriptional corepressors promote cancer cell survival and migration/invasion. senses cellular metabolism via a regulatory dehydrogenase domain, is antagonized by p14/p19ARF tumor suppressors. substrate 4-methylthio-2-oxobutyric acid (MTOB) can act as inhibitor at high concentrations, cytotoxic to cells. MTOB induced apoptosis was p53-independent, correlated with the derepression of pro-apoptotic repression target Bik, rescued over-expression or Bik silencing. did not induce in...
Adeno-associated virus (AAV)-induced dorsal root ganglia (DRG) toxicity has been observed in several nonclinical species, where lesions are characterized by neuronal degeneration/necrosis, nerve fiber degeneration, and mononuclear cell infiltration. As AAV vectors become an increasingly common platform for novel therapeutics, non-invasive biomarkers needed to better characterize manage the risk of DRG neurotoxicity both clinical studies. Based on biological relevance, reagent availability,...
Abstract The alternative reading frame (ARF) tumor suppressor exerts both p53-dependent and p53-independent activities critical to the prevention of cancer in mice humans. Recent evidence from mouse models suggests that when p53 is absent, further loss ARF can widen spectrum, potentiate invasion metastasis. A major target activity COOH-terminal binding protein (CtBP) family metabolically regulated transcriptional corepressors, which are degraded upon acute exposure protein. CtBPs activated...
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is metabolized to enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), found in the urine virtually all people exposed tobacco products. We assessed carcinogenicity male F-344 rats (R)-NNAL (5 ppm drinking water), (S)-NNAL ppm), NNK ppm) and racemic NNAL (10 analyzed DNA adduct formation lung pancreas these after 10, 30, 50 70 weeks treatment. All test compounds induced a high incidence tumors, both adenomas carcinomas....
The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project ( www.toxpath.org/inhand.asp ) is a joint initiative the societies toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), North America (STP) to develop an internationally accepted nomenclature proliferative nonproliferative lesions in laboratory animals. purpose this publication provide standardized classifying observed most tissues organs dog used nonclinical safety...
Harmonization of diagnostic terminology used during the histopathologic analysis rodent tissue sections from nonclinical toxicity studies will improve consistency data sets produced by laboratories located around world. The INHAND Project ( International Nomenclature and Diagnostic Criteria for Lesions in Rats Mice) is a cooperative enterprise 4 major societies toxicologic pathology to develop globally accepted standard vocabulary proliferative nonproliferative lesions rodents. A prior...
Two Boxer dogs developed progressive ataxia in association with a neoplastic infiltration of the spinal leptomeninges. In first dog, leptomeningeal neoplasm encompassed entire cord and ventral aspect brainstem extended bilaterally into piriform lobes. second, surrounded C1–C3 segments without involvement brain or parenchyma. both dogs, cells had variably distinct cell borders, clear to eosinophilic cytoplasm, round ovoid hyperchromatic nucleus. Neoplastic were immunopositive for Olig2...
A 16-week-old sexually intact male Whippet was evaluated because of a 1-week history firm abdominal swelling.The puppy had been obtained from breeder at 9 weeks age and healthy until the swelling noticed.
Bluetongue virus (BTV), a member of genus Orbivirus, family Reoviridae, is non-enveloped with double shelled structure and 10 segmented stranded RNA genome. The segment L2 encodes an outer capsid serotype specific viral protein VP2. BTV 1 (BTV-1) novel primer pair, forward (1240-1271 bp) reverse (1844-1813 bp), was designed using VP2 gene sequences available in GenBank to amplify 1240-1844 bp region because two hypervariable three conserved regions have been reported within these 604...
Mutations in the ABCB4 gene lead to a wide-spectrum of rare liver diseases including progressive familial intrahepatic cholestasis type 3 (PFIC3) and low-phospholipid associated cholelithiasis (LPAC) syndrome. PFIC3 patients develop symptoms during late infancy, severe itching, jaundice, failure thrive. The condition may progress childhood or adulthood. This is highly unmet medical where transplantation only option correct this disease. Recently, exciting data suggested that restoration...
Three young domestic shorthair cats were presented for necropsy with similar histories of slowly progressive visual dysfunction and neurologic deficits. Macroscopic examination each cat revealed cerebral cerebellar atrophy, dilated lateral ventricles, slight brown discoloration the gray matter. Histologically, there was bilateral loss neurons within limbic, motor, somatosensory, visual, and, to a lesser extent, vestibular systems extensive astrogliosis in affected regions all 3 cases. Many...
Present paper describes the dynamics of bovine herpes virus-1(BoHV-1) in breeding cattle under different housing, feeding and watering practices. Organized farms A, B, C, D were selected for this study. In farm animals housed large open shed with common grazing drinking area. Farm B had individual pens separate facility but watering/drinking facility. C pens, each animal. possessed modern housing system feeding, facility, restricted personnel entry better bio-security set up. The blood semen...
Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There strong evidence that tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role carcinogenesis caused by tobacco products. NNK racemic NNAL are reported to induce lung pancreatic tumors rats. The carcinogenicity Fischer 344 rats NNK, NNAL, enantiomers ( R)-NNAL S)-NNAL has been studied...
Two adult sibling red-handed tamarins ( Saguinus midas) presented with weight loss and multifocal skin masses. A biopsy revealed pyogranulomatous dermatitis intrafollicular Demodex sp. mites. Subsequent scrapes confirmed the presence of live mites within lesions. Initial treatment topical oral ivermectin was unsuccessful, lesions continued to progress. single dose fluralaner (Bravecto®, Merck Animal Health, Kenilworth, New Jersey, 07033, USA; 28.125 mg po) administered each animal...
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide; however, mutational properties HCC-associated carcinogens remain largely uncharacterized. We hypothesized that mechanisms underlying chemical-induced HCC can be characterized by evaluating spectra these tumors. To test this hypothesis, we performed exome sequencing B6C3F1/N HCCs arose either spontaneously in vehicle controls ( n = 3) or due to chronic exposure gingko biloba extract (GBE; 4)...
The 2015 Annual National Toxicology Program Satellite Symposium, entitled “Pathology Potpourri” was held in Minneapolis, Minnesota, at the American College of Veterinary Pathologists/American Society for Clinical Pathology/Society Toxicologic Pathology combined meeting. goal this symposium is to present and discuss diagnostic pathology challenges or nomenclature issues. Because meeting, both laboratory domestic animal cases were presented. This article presents summaries speakers’ talks,...
Bluetongue virus (BTV), a member of genus Orbivirus, family Reoviridae, is non-enveloped with double shelled structure and ten segmented stranded (ds) RNA genome. The segment S7 encodes an inner capsid serogroup specific viral protein VP7. To amplify coding region VP7 gene BTV, new primers, forward primer (18–38 bp) reverse (1156–1136 bp), were designed using sequences available in GenBank. This pair successfully amplified cell culture adapted Indian isolates BTV belonging to two different...