A5034188920- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- T-cell and Retrovirus Studies
- Liver physiology and pathology
- Growth Hormone and Insulin-like Growth Factors
- Effects of Radiation Exposure
- Congenital heart defects research
- Chromosomal and Genetic Variations
- Immune cells in cancer
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Telomeres, Telomerase, and Senescence
- Renal and related cancers
- Advanced biosensing and bioanalysis techniques
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer Research and Treatments
- Cancer, Stress, Anesthesia, and Immune Response
- Pancreatic function and diabetes
- Viral-associated cancers and disorders
- Genetics, Aging, and Longevity in Model Organisms
- Birth, Development, and Health
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
Abcombi Biosciences (United States)
2016-2020
Cleveland BioLabs (United States)
2008-2017
Buffalo BioLabs
2014-2017
University of California, San Diego
1995-2008
Roswell Park Comprehensive Cancer Center
2008
Cleveland Clinic Lerner College of Medicine
2008
Sanford Burnham Prebys Medical Discovery Institute
2008
Institute for Medical Research
2008
Howard Hughes Medical Institute
1996-2004
Baylor College of Medicine
2001
The toxicity of ionizing radiation is associated with massive apoptosis in radiosensitive organs. Here, we investigate whether a drug that activates signaling mechanism used by tumor cells to suppress can protect healthy from the harmful effects radiation. We studied CBLB502, polypeptide derived Salmonella flagellin binds Toll-like receptor 5 (TLR5) and nuclear factor–κB signaling. A single injection CBLB502 before lethal total-body irradiation protected mice both gastrointestinal...
During development of the mammalian pituitary gland specific hormone-producing cell types, critical in maintaining homeostasis, emerge a spatially and temporally fashion from an ectodermal primordium. We have investigated molecular basis generating diverse phenotypes common precursor, providing vivo vitro evidence that their involves three sequential phases signaling events action gradient at boundary. In first phase, BMP4 signal ventral diencephalon, expressing BMP4, Wnt5a, FGF8, represents...
Pitx1 is a Bicoid-related homeodomain factor that exhibits preferential expression in the hindlimb, as well developing anterior pituitary gland and first branchial arch. Here, we report gene-deleted mice exhibit striking abnormalities morphogenesis growth of resulting limb structural changes tibia fibula patterning alterations patella proximal tarsus, to more closely resemble corresponding forelimb structures. Deletion locus results decreased distal hindlimb-specific marker, T-box factor,...
Constitutive p16 Ink4a expression, along with senescence-associated β-galactosidase (SAβG), are commonly accepted biomarkers of senescent cells (SCs).Recent reports attributed improvement the healthspan aged mice following -positive cell killing to eradication accumulated SCs.However, detection /SAβG-positive macrophages in adipose tissue old and peritoneal cavity young animals injection alginate-encapsulated SCs has raised concerns about exclusivity these markers for SCs.Here we report that...
Senescent cells (SCs) have been considered a source of age-related chronic sterile systemic inflammation and target for anti-aging therapies. To understand mechanisms controlling the amount SCs, we analyzed phenomenon rapid clearance human senescent fibroblasts implanted into SCID mice, which can be overcome when SCs were embedded alginate beads preventing them from immunocyte attack. identify putative SC killers, content cell populations in lavage capsules formed around SC-containing beads....
The circadian clock controls many physiological parameters including immune response to infectious agents, which is mediated by activation of the transcription factor NF-κB. It widely accepted that regulation based on periodic changes in gene expression are triggered transcriptional activity CLOCK/BMAL1 complex. Through use a mouse model system we show daily variations intensity NF-κB variety immunomodulators core protein CLOCK, can up-regulate NF-κB–mediated absence BMAL1; moreover, BMAL1...
ABSTRACT Pituitary gland development serves as an excellent model system in which to study the emergence of distinct cell types from a common primordium mammalian organogenesis. We have investigated role morphogen Sonic hedgehog (SHH) outgrowth and differentiation pituitary using loss-and gain-of-function studies transgenic mice. Shh is expressed throughout ventral diencephalon oral ectoderm, but its expression subsequently absent nascent Rathke’s pouch soon it becomes morphologically...
Targeted insertional disruption of the mouse estrogen receptor-alpha (ER alpha) gene has provided a genetic model in which to test hypotheses that estrogens exert important effects development and homeostatic functions anterior pituitary gland, particularly lactotroph gonadotroph cell types. Analysis ER alpha gene-disrupted mice reveals marked reduction PRL mRNA decrease number, but normal specification phenotype. Gonadotropin levels female are elevated, consistent with previously described...
Adult tissues undergo continuous cell turnover in response to stress, damage, or physiological demand. New differentiated cells are generated from dedicated facultative stem self-renewing cells. Here we describe a different strategy for tissue maintenance, distinct that observed We report the presence of nestin-expressing adult perilumenal region mature anterior pituitary and, using genetic inducible fate mapping, demonstrate they serve generate subsets all six terminally endocrine types...
Significance Understanding the mechanisms underlying development of senescence and consequences related to accumulation senescent cells is a major focus ongoing research. Our report shows that express form oxidized vimentin on their cell surface secreted into blood senescence-prone senescence-accelerated mouse prone 8 mice. Given growing evidence proteins are involved in human diseases, detection monitoring like malondialdehyde-modified certain become vital noninvasive biomarker for studying...
Significance Toll-like receptor 5 (TLR5) is an innate immunity that specifically recognizes and triggers immune response to bacterial flagellins. In addition resistance Salmonella infection, TLR5 agonists protect mammals from radiation have anticancer effects, including suppression of tumor metastases. Using mouse models, we defined the liver as a major target for agonists. Administration pharmacologically optimized flagellin derivative CBLB502 leads rapid activation prosurvival nuclear...
A family of p160 coactivators was initially identified based on ligand-dependent interactions with nuclear receptors and thought to function, in part, by recruiting CREB-binding protein/p300 several classes transcription factors. One the factors, p/CIP/AIB1, often amplified overexpressed breast cancer, also exhibits particularly strong interaction protein/p300. In this manuscript, we report that p/CIP, which regulated transfer from cytoplasm nucleus, is required for normal somatic growth...
Pax6 , a highly conserved member of the paired homeodomain transcription factor family that plays essential roles in ocular, neural, and pancreatic development effects asymmetric transient dorsal expression during pituitary development, with its extinguished before ventral → appearance specific cell types. Analysis Small eye −/− mouse mutants reveals dorsoventral axis gland becomes ventralized, extension transcriptional determinants types, particularly PFrk . This ventralization is followed...
The development of healthspan-extending pharmaceuticals requires quantitative estimation age-related progressive physiological decline.In humans, individual health status can be quantitatively assessed by means a frailty index (FI), parameter which reflects the scale accumulation deficits.However, adaptation this methodology to animal models is challenging task since it includes multiple subjective parameters.Here we report non-invasive procedure estimate biological age an creating (PFI).We...
Pituitary cell types arise in a temporally and spatially specific fashion, response to combinatorial actions of transcription factors induced by transient signaling gradients. The critical transcriptional determinants the two pituitary that express pro-opiomelanocortin (POMC) gene, anterior lobe corticotropes, producing adrenocorticotropin, intermediate melanotropes, melanocyte-stimulating hormone (MSHα), have remained unknown. Here, we report member T-box gene family, Tbx19 , which is...
A critical aspect of mammalian development involves the actions dedicated repressors/corepressors to prevent unregulated gene activation programs that would initiate specific cell determination events. While role NCoR/SMRT corepressors in nuclear receptor is well documented, we here report a previously unrecognized functional interaction between SMRT and forkhead protein, FOXP1, required for cardiac growth regulation macrophage differentiation. Our studies demonstrate FOXP1 define biological...
AbstractThe bulge region of the hair follicle serves as a repository for epithelial stem cells that can regenerate in each growth cycle and contribute to epidermis regeneration upon injury. Here we describe population multipotential bulge; these be identified by fluorescence transgenic nestin-GFP mice. The morphological features suggest they maintain close associations with other surrounding niche. Upon explantation, give rise neurosphere-like structures vitro. When are permitted...
There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after exposure and counteract effects on hematopoietic system gastrointestinal tract that contribute its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity rodents radioprotective non-human primates....