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  • Victoria M Virador
Victoria M Virador

Victoria M Virador

PhD

About

44
Publications
25,124
Reads
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2,207
Citations
Additional affiliations
June 2003 - June 2013
National Institutes of Health
Position
  • Senior Researcher

Publications

Publications (44)
Article
Understanding cellular processes involved in wound healing is very important given that there are diseases, such as diabetes, in which wounds do not heal. To model tissue regeneration, we focus on two cellular processes: cellular proliferation, to replace cells lost to the wound, and cell motility, activated at the wound edges. We address these two...
Chapter
This overview of the current state of skin wound healing includes in vitro and in vivo approaches along with some recent clinical trials. From an introduction to wound healing, to tissue engineering as applied to the skin, we cover the basis for the current wound care techniques as well as novel and promising approaches. Special emphasis is given t...
Article
Full-text available
Introduction: The development of one standard, simplified in vitro three-dimensional tissue model suitable to biological and pathological investigation and drug-discovery may not yet be feasible, but standardized models for individual tissues or organs are a possibility. Tissue bioengineering, while concerned with finding methods of restoring func...
Article
Full-text available
We developed protocols for isolation and characterization of mesenchymal progenitors from murine dermis. Our protocols are part of a more general isolation procedure starting with neonatal murine skin, which has been described in detail by U. Lichti and coauthors (Nat Protoc 3(5):799-810, 2008). We list Lichti's procedures in an abbreviated form as...
Article
Tissues are three-dimensional (3D) entities as is the tumor that arises within them. Though disaggregated cancerous tissues have produced numerous cell lines for basic and applied research, it is generally agreed that these lines are poor models of in vivo phenomena. In this review we focus on in vitro 3D models used in cancer research, particularl...
Article
BAG3 is a pro-survival pro-invasion chaperone. We hypothesized that human BAG3 overexpression in murine breast would contribute to mammary tumorigenesis. We generated transgenic mice ectopically expressing hBAG3 in the mammary gland under the control of the Mouse Mammary Tumor Viral promoter (MMTV-hBAG3). hBAG3 was expressed in luminal cells throug...
Article
Full-text available
Recent work identified L-asparaginase (L-ASP) as a putative therapeutic target for ovarian cancer. We hypothesized L-ASP, a dysregulator of glycosylation, would interrupt the local microenvironment, affecting the ovarian cancer cell—endothelial cell interaction and thus angiogenesis without cytotoxic effects. Ovarian cancer cell lines and human mic...
Article
We have previously shown that BAG3 is a pro-survival protein in human cancer lines subject to stress. BAG3 overexpression also mediates a decrease in migration and adhesion to matrix in MDA-435 breast cancer cells; this is reversed in a BAG3 mutant with a deleted proline-rich domain (PXXP). Additionally, BAG3 induces the secreted molecule CCN-1 to...
Article
The majority of solid tumors are carcinomas. To invade, carcinomas must lose cell-cell adhesion and acquire motility: a process termed epithelial-to-mesenchymal transition (EMT). EMT is a highly conserved cellular program that enables polarized, immotile epithelial cells to convert to motile mesenchymal-like cells. Secretory leukocyte protease inhi...
Article
The full-length cDNA sequence (P93622_VITVI) of polyphenol oxidase (PPO) cDNA from grape Vitis vinifera L., cv Grenache, was found to encode a translated protein of 607 amino acids with an expected molecular weight of ca. 67 kDa and a predicted pI of 6.83. The translated amino acid sequence was 99%, identical to that of a white grape berry PPO (1)...
Article
Full-text available
Chaperone protein quantity may regulate the balance of proteins involved in invasion and malignancy. BAG3 is a co-chaperone and pro-survival protein that has been implicated in adhesion, migration, and metastasis. We reported that BAG3 overexpression in MDA435 human breast cancer cells results in a significant decrease in migration and adhesion to...
Article
Expression of the PMLRARalpha fusion dominant-negative oncogene in the epidermis of transgenic mice resulted in spontaneous skin tumors attributed to changes in both the PML and RAR pathways [Hansen et al., Cancer Res 2003; 63:5257-5265]. To determine the contribution of PML to skin tumor susceptibility, transgenic mice were generated on an FVB/N b...
Data
A fraction of BAG3 co-localizes with mitochondria in early STS-mediated stress. BAG3 stained cells (green) loaded with Mito Tracker (red) and counterstained with DAPI (blue). Arrows show colocalization in yellow. At higher STS doses, there is loss of the BAG3 green signal and a generalized uptake of Mito Tracker in cell nuclei (arrow head) indicati...
Data
BAG3 is transiently induced in early STS-mediated stress. A. Flow cytometry of MDA435 cells stained for BAG3 (secondary Alexa 666 anti Rabbit) and subject to increasing STS doses. B. MDA435 cells stained for BAG3 after 4 h STS exposure (secondary Alexa 594 anti Rabbit). (3.57 MB TIF)
Data
Inhibition of caspases and proteasome provides collaborative protection of BAG3. A. Proteasome inhibition with lactacystyin (1 µM, 4 hr preincubation) in MDA-435 cells overexpressing BAG3 or BAG3-dPXXP provides partial protection of BAG3. B. Lactacystin in combination with zVAD provides near full protection of BAG3, similar to MG-132. (0.29 MB TIF)
Data
Commonly used ‘housekeeping proteins’ are degraded by STS in HeLa and MDA 435 cells. A. HeLa cells overexpressing BAG3. BAG3 signal disappears with increasing time of exposure to 2 µM STS. GAPDH (re-blot) likewise disappears with STS exposure. B. MDA435 cells. BAG3 signal disappears with STS and is protected by addition of MG-132 or MG-132 and zVAD...
Data
Disappearance of the BAG3 signal by siRNA. MDA435-Neo cells were exposed to 200 nM BAG3 siRNA or scramble control for 72 hours followed by addition of vehicle control or 2µM STS for additional 6 hrs. Immunoblot demonstrates silencing of BAG3. (0.17 MB TIF)
Article
Full-text available
Caspase-mediated cleavage and proteasomal degradation of ubiquitinated proteins are two independent mechanisms for the regulation of protein stability and cellular function. We previously reported BAG3 overexpression protected ubiquitinated clients, such as AKT, from proteasomal degradation and conferred cytoprotection against heat shock. We hypoth...
Article
Full-text available
The skin contains two known subpopulations of stem cells/epidermal progenitors: a basal keratinocyte population found in the interfollicular epithelium and cells residing in the bulge region of the hair follicle. The major role of the interfollicular basal keratinocyte population may be epidermal renewal, whereas the bulge population may only be ac...
Article
CAIR-1/BAG-3 is a stress and survival protein that has been shown to bind SH3 domain-containing proteins through its proline-rich (PXXP) domain. Because stress and survival pathways are active during invasion and metastasis, we hypothesized that CAIR-1 is a regulator of signaling pathways that modulate cell adhesion and migration. MDA-435 human bre...
Chapter
The search for effective cancer therapies is one of the foremost priorities of modern-day research. In recent times, enormous strides have been made in the understanding of the molecular events that underlie cancer progression and in the development of promising therapies against relevant molecular targets. The molecular signalling pathways that mo...
Article
Melatonin, a derivative of tryptophan that is present in all vertebrates, was first described in bovine pineal gland. It is known that melatonin is a highly conserved molecule, present also in unicellular organisms and plants. Several effects of melatonin have been described, including receptor- and non-receptor-mediated actions. Herein, we studied...
Article
Full-text available
The construction of transgenic FVB/N mice targeting the PMLRARA fusion gene under the control of a human MRP8 promoter recapitulated the phenotype of acute promyelocytic leukemia but had the unexpected result of multiple squamous papillomas of the skin (Brown et al., PROC: Natl. Acad. Sci. USA, 94:2551-2556, 1997). In addition, transgenic MRP8-PMLR...
Article
In this study, we used melb-a melanoblasts as a model to study mechanisms involved in stimulating melanocyte function in vitiliginous skin following exposure to 8-methoxypsoralen (8MOP). Melanin content and tyrosinase activity increased 3- and 7-fold, respectively, in melanoblasts treated with 8MOP for 6 d compared with untreated controls. The intr...
Article
Many melanocyte or skin equivalent models have been used to evaluate the potential efficacy of melanogenic compounds to regulate pigmentation, but there has been great variation in results, partially stemming from the use of different cell lines and diverse conditions for the melanogenic assays. In an earlier report, we optimized a microtiter forma...
Article
Oculocutaneous albinism (OCA) is caused by reduced or deficient melanin pigmentation in the skin, hair, and eyes. OCA has different phenotypes resulting from mutations in distinct pigmentation genes involved in melanogenesis. OCA type 2 (OCA2), the most common form of OCA, is an autosomal recessive disorder caused by mutations in the P gene, the fu...
Article
Full-text available
Cutaneous pigmentation is determined by the amounts of eumelanin and pheomelanin synthesized by epidermal melanocytes and is known to protect against sun-induced DNA damage. The synthesis of eumelanin is stimulated by the binding of alpha-melanotropin (alpha-melanocyte-stimulating hormone) to the functional melanocortin 1 receptor (MC1R) expressed...
Article
The epidermal melanin unit in human skin is composed of melanocytes and keratinocytes. Melanocytes, located in the basal layer of the epidermis, manufacture melanin-loaded organelles called melanosomes. Through their dendritic processes, melanocytes distribute melanosomes to neighboring keratinocytes, where their presence confers to the skin its ch...
Article
Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well k...
Article
The effects of all-trans retinoic acid (RA) on melanogenesis and the mechanism of its action in topical treatment have not been elucidated. The purpose of this study was to determine the effects of RA on melanogenesis in the pigmented skin equivalent as well as in monolayer culture of melanocytes, and to determine whether RA, hydroquinone (HQ), and...
Article
In this study, three different phenolic (anthocyanin, other flavonoid, and phenolic acid) fractions from wine and a condensed tannin preparation from sorghum were tested for their effects on melanogenesis of normal cells and growth of human melanoma cells. The wine phenolic fractions decreased melanogenic activity (tyrosinase activity) at concentra...
Article
The switch between the synthesis of eu- and pheomelanins is modulated by the interaction of two paracrine signaling molecules, alpha-melanocyte stimulating hormone (MSH) and agouti signal protein (ASP), which interact with melanocytes via the MSH receptor (MC1R). Comparison of the primary sequence of ASP with the known MSH pharmacophore provides no...
Article
Switching between production of eumelanin or pheomelanin in follicular melanocytes is responsible for hair color in mammals; in mice, this switch is controlled by the agouti locus, which encodes agouti signal protein (ASP) through the action of melanocortin receptor 1. To study expression and processing patterns of ASP in the skin and its regulatio...
Article
Full-text available
Glutathione (GSH) and cysteine (CysH) have both been implicated in the biogenesis of the pheomelanin precursor 5-S-cysteinyldopa (5-S-CD). However, recent studies have shown that only CysH is transported across the membrane of isolated melanosomes, and that the positive regulation of CysH in pigment cells leads to an increased production of 5-S-CD....
Article
Varied effects of chemical or biological compounds on mammalian pigmentation have been reported by many groups, but to date, no standardized method has established necessary and/or optimal parameters for testing such agents. A standardized method has been developed to screen compounds with potential effects on pigmentation. The protocol comprises b...
Article
To discover safe and effective topical skin-lightening agents, we have evaluated alkyl esters of the natural product gentisic acid (GA), which is related to our lead compound methyl gentisate (MG), and four putative tyrosinase inhibitors, utilizing mammalian melanocyte cell cultures and cell-free extracts. Desirable characteristics include the abil...
Article
The synthesis of pheomelanin requires the incorporation of thiol-containing compound(s) during the process of mammalian melanogenesis. Since melanins are produced only in specialized, membrane-bound organelles, known as melanosomes, such thiol donor(s) must cross the membrane barrier from the cytosol to the melanosome interior. Cysteine and/or glut...
Article
Molecular and biochemical mechanisms which modulate the switch between black/brown eumelanins and yellow/red pheomelanins involve the opposing effects of two intercellular signaling molecules, α-melanocyte stimulating hormone (MSH) and agouti signal protein (ASP). ASP is an antagonist of MSH signaling mediated by the melanocyte specific MSH recepto...
Article
Thesis (M.S.)--University of California, Davis, 1993. Degree granted in Food Science and Technology.

Questions

Questions (3)
Question
I was wondering if members have experience with this organization and what is the funding mechanism for this kind of concept. Thanks
Question
Can somebody recommend a reference that addresses this point?
Appreciate
Victoria Virador

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Projects (2)
Project
What combination of scaffolding, cells, and small molecule would work best in wound healing creams or other devices.