The Experts below are selected from a list of 69069 Experts worldwide ranked by ideXlab platform
Michael J Nemeth - One of the best experts on this subject based on the ideXlab platform.
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Non-canonical Wnt Signaling pathways in hematopoiesis.
Immunologic Research, 2010Co-Authors: Kathleen Kokolus, Michael J NemethAbstract:Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal and initiation of hematopoietic differentiation. Multiple Signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. The function of the canonical Wnt Signaling pathway, which utilizes β-catenin to regulate gene expression, has been extensively studied in hematopoiesis. However, there is a growing body of evidence that the other Wnt Signaling pathways, termed non-canonical, also play an important role. In this review, we will discuss the regulation of hematopoiesis by the Wnt Signaling pathways, focusing on the potential functions of non-canonical Wnt Signaling pathways.
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Non-canonical Wnt Signaling pathways in hematopoiesis.
Immunologic research, 2009Co-Authors: Kathleen Kokolus, Michael J NemethAbstract:Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal and initiation of hematopoietic differentiation. Multiple Signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. The function of the canonical Wnt Signaling pathway, which utilizes beta-catenin to regulate gene expression, has been extensively studied in hematopoiesis. However, there is a growing body of evidence that the other Wnt Signaling pathways, termed non-canonical, also play an important role. In this review, we will discuss the regulation of hematopoiesis by the Wnt Signaling pathways, focusing on the potential functions of non-canonical Wnt Signaling pathways.
Jae Il Park - One of the best experts on this subject based on the ideXlab platform.
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Wnt Signaling in cancer: therapeutic targeting of Wnt Signaling beyond β-catenin and the destruction complex.
Experimental & molecular medicine, 2020Co-Authors: Youn Sang Jung, Jae Il ParkAbstract:Wnt/β-catenin Signaling is implicated in many physiological processes, including development, tissue homeostasis, and tissue regeneration. In human cancers, Wnt/β-catenin Signaling is highly activated, which has led to the development of various Wnt Signaling inhibitors for cancer therapies. Nonetheless, the blockade of Wnt Signaling causes side effects such as impairment of tissue homeostasis and regeneration. Recently, several studies have identified cancer-specific Wnt Signaling regulators. In this review, we discuss the Wnt inhibitors currently being used in clinical trials and suggest how additional cancer-specific regulators could be utilized to treat Wnt Signaling-associated cancer.
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Wnt Signaling in cancer: therapeutic targeting of Wnt Signaling beyond β-catenin and the destruction complex
Experimental & Molecular Medicine, 2020Co-Authors: Youn Sang Jung, Jae Il ParkAbstract:More effective treatments for cancer could be developed by targeting Signaling pathway regulators that are expressed solely in cancer cells. Disruption to a major Signaling pathway known as Wnt, which is involved in processes including cell proliferation, tissue homeostasis and tissue regeneration, is now recognized as a significant contributor to the development of certain cancers. Jae-Il Park and Youn-Sang Jung at the University of Texas MD Anderson Cancer Center, Houston, USA, reviewed recent research into Wnt Signaling in cancer and possible therapies. Scientists have developed Wnt inhibitors for cancer treatment, but these have detrimental side effects including skeletal degeneration and abdominal pain. New studies suggest there are Wnt Signaling regulators that are specifically expressed in cancer cells, which may prove to be more effective drug targets than blocking Wnt Signaling as a whole. Wnt/β-catenin Signaling is implicated in many physiological processes, including development, tissue homeostasis, and tissue regeneration. In human cancers, Wnt/β-catenin Signaling is highly activated, which has led to the development of various Wnt Signaling inhibitors for cancer therapies. Nonetheless, the blockade of Wnt Signaling causes side effects such as impairment of tissue homeostasis and regeneration. Recently, several studies have identified cancer-specific Wnt Signaling regulators. In this review, we discuss the Wnt inhibitors currently being used in clinical trials and suggest how additional cancer-specific regulators could be utilized to treat Wnt Signaling-associated cancer.
Roel Nusse - One of the best experts on this subject based on the ideXlab platform.
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Lentiviral vectors to probe and manipulate the Wnt Signaling pathway.
PLOS ONE, 2010Co-Authors: Christophe Fuerer, Roel NusseAbstract:Background The Wnt Signaling pathway plays key roles in development, adult tissue homeostasis and stem cell maintenance. Further understanding of the function of Wnt Signaling in specific cell types could benefit from lentiviral vectors expressing reporters for the Wnt pathway or vectors interfering with Signaling. Methodology/Principal Findings We have developed a set of fluorescent and luminescent lentiviral vectors that report Wnt Signaling activity and discriminate between negative and uninfected cells. These vectors possess a 7xTcf-eGFP or 7xTcf-FFluc (Firefly Luciferase) reporter cassette followed by either an SV40-mCherry or SV40-PuroR (puromycin N-acetyltransferase) selection cassette. We have also constructed a vector that allows drug-based selection of cells with activated Wnt Signaling by placing PuroR under the control of the 7xTcf promoter. Lastly, we have expressed dominant-negative Tcf4 (dnTcf4) or constitutively active beta-catenin (β-catenin4A) from the hEF1α promoter in a SV40-PuroR or SV40-mCherry backbone to create vectors that inhibit or activate the Wnt Signaling pathway. These vectors will be made available to the scientific community through Addgene. Conclusions These novel lentiviruses are efficient tools to probe and manipulate Wnt Signaling. The use of a selection cassette in Wnt-reporter viruses enables discriminating between uninfected and non-responsive cells, an important requirement for experiments where selection of clones is not possible. The use of a chemiluminescent readout enables quantification of Signaling. Finally, selectable vectors can be used to either inhibit or activate the Wnt Signaling pathway. Altogether, these vectors can probe and modulate the Wnt Signaling pathway in experimental settings where persistence of the transgene or gene transfer cannot be accomplished by non-viral techniques.
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Wnt Signaling regulates pancreatic β cell proliferation
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Ingrid C Rulifson, Roel Nusse, Satyajit K Karnik, Patrick W Heiser, Derk Ten Berge, Hainan Chen, Xueying Gu, Makoto Mark Taketo, Matthias HebrokAbstract:There is widespread interest in defining factors and mechanisms that stimulate proliferation of pancreatic islet cells. Wnt Signaling is an important regulator of organ growth and cell fates, and genes encoding Wnt-Signaling factors are expressed in the pancreas. However, it is unclear whether Wnt Signaling regulates pancreatic islet proliferation and differentiation. Here we provide evidence that Wnt Signaling stimulates islet β cell proliferation. The addition of purified Wnt3a protein to cultured β cells or islets promoted expression of Pitx2, a direct target of Wnt Signaling, and Cyclin D2, an essential regulator of β cell cycle progression, and led to increased β cell proliferation in vitro. Conditional pancreatic β cell expression of activated β-catenin, a crucial Wnt signal transduction protein, produced similar phenotypes in vivo, leading to β cell expansion, increased insulin production and serum levels, and enhanced glucose handling. Conditional β cell expression of Axin, a potent negative regulator of Wnt Signaling, led to reduced Pitx2 and Cyclin D2 expression by β cells, resulting in reduced neonatal β cell expansion and mass and impaired glucose tolerance. Thus, Wnt Signaling is both necessary and sufficient for islet β cell proliferation, and our study provides previously unrecognized evidence of a mechanism governing endocrine pancreas growth and function.
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Wnt Signaling in disease and in development
Cell research, 2005Co-Authors: Roel NusseAbstract:The highly conserved Wnt secreted proteins are critical mediators of cell-to-cell Signaling during development of animals. Recent biochemical and genetic analyses have led to significant insight into understanding how Wnt signals work. The catalogue of Wnt Signaling components has exploded. We now realize that multiple extracellular, cytoplasmic, and nuclear components modulate Wnt Signaling. Moreover, receptor-ligand specificity and multiple feedback loops determine Wnt Signaling outputs. It is also clear that Wnt signals are required for adult tissue maintenance. Perturbations in Wnt Signaling cause human degenerative diseases as well as cancer.
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the Wnt Signaling pathway in development and disease
Annual Review of Cell and Developmental Biology, 2004Co-Authors: Catriona Y Logan, Roel NusseAbstract:Tight control of cell-cell communication is essential for the generation of a normally patterned embryo. A critical mediator of key cell-cell Signaling events during embryogenesis is the highly conserved Wnt family of secreted proteins. Recent biochemical and genetic analyses have greatly enriched our understanding of how Wnts signal, and the list of canonical Wnt Signaling components has exploded. The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt Signaling levels. In addition, receptor-ligand specificity and feedback loops help to determine Wnt Signaling outputs. Wnts are required for adult tissue maintenance, and perturbations in Wnt Signaling promote both human degenerative diseases and cancer. The next few years are likely to see novel therapeutic reagents aimed at controlling Wnt Signaling in order to alleviate these conditions.
Kathleen Kokolus - One of the best experts on this subject based on the ideXlab platform.
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Non-canonical Wnt Signaling pathways in hematopoiesis.
Immunologic Research, 2010Co-Authors: Kathleen Kokolus, Michael J NemethAbstract:Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal and initiation of hematopoietic differentiation. Multiple Signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. The function of the canonical Wnt Signaling pathway, which utilizes β-catenin to regulate gene expression, has been extensively studied in hematopoiesis. However, there is a growing body of evidence that the other Wnt Signaling pathways, termed non-canonical, also play an important role. In this review, we will discuss the regulation of hematopoiesis by the Wnt Signaling pathways, focusing on the potential functions of non-canonical Wnt Signaling pathways.
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Non-canonical Wnt Signaling pathways in hematopoiesis.
Immunologic research, 2009Co-Authors: Kathleen Kokolus, Michael J NemethAbstract:Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal and initiation of hematopoietic differentiation. Multiple Signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. The function of the canonical Wnt Signaling pathway, which utilizes beta-catenin to regulate gene expression, has been extensively studied in hematopoiesis. However, there is a growing body of evidence that the other Wnt Signaling pathways, termed non-canonical, also play an important role. In this review, we will discuss the regulation of hematopoiesis by the Wnt Signaling pathways, focusing on the potential functions of non-canonical Wnt Signaling pathways.
Youn Sang Jung - One of the best experts on this subject based on the ideXlab platform.
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Wnt Signaling in cancer: therapeutic targeting of Wnt Signaling beyond β-catenin and the destruction complex.
Experimental & molecular medicine, 2020Co-Authors: Youn Sang Jung, Jae Il ParkAbstract:Wnt/β-catenin Signaling is implicated in many physiological processes, including development, tissue homeostasis, and tissue regeneration. In human cancers, Wnt/β-catenin Signaling is highly activated, which has led to the development of various Wnt Signaling inhibitors for cancer therapies. Nonetheless, the blockade of Wnt Signaling causes side effects such as impairment of tissue homeostasis and regeneration. Recently, several studies have identified cancer-specific Wnt Signaling regulators. In this review, we discuss the Wnt inhibitors currently being used in clinical trials and suggest how additional cancer-specific regulators could be utilized to treat Wnt Signaling-associated cancer.
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Wnt Signaling in cancer: therapeutic targeting of Wnt Signaling beyond β-catenin and the destruction complex
Experimental & Molecular Medicine, 2020Co-Authors: Youn Sang Jung, Jae Il ParkAbstract:More effective treatments for cancer could be developed by targeting Signaling pathway regulators that are expressed solely in cancer cells. Disruption to a major Signaling pathway known as Wnt, which is involved in processes including cell proliferation, tissue homeostasis and tissue regeneration, is now recognized as a significant contributor to the development of certain cancers. Jae-Il Park and Youn-Sang Jung at the University of Texas MD Anderson Cancer Center, Houston, USA, reviewed recent research into Wnt Signaling in cancer and possible therapies. Scientists have developed Wnt inhibitors for cancer treatment, but these have detrimental side effects including skeletal degeneration and abdominal pain. New studies suggest there are Wnt Signaling regulators that are specifically expressed in cancer cells, which may prove to be more effective drug targets than blocking Wnt Signaling as a whole. Wnt/β-catenin Signaling is implicated in many physiological processes, including development, tissue homeostasis, and tissue regeneration. In human cancers, Wnt/β-catenin Signaling is highly activated, which has led to the development of various Wnt Signaling inhibitors for cancer therapies. Nonetheless, the blockade of Wnt Signaling causes side effects such as impairment of tissue homeostasis and regeneration. Recently, several studies have identified cancer-specific Wnt Signaling regulators. In this review, we discuss the Wnt inhibitors currently being used in clinical trials and suggest how additional cancer-specific regulators could be utilized to treat Wnt Signaling-associated cancer.
