The Experts below are selected from a list of 15621 Experts worldwide ranked by ideXlab platform
Melissa A Kinney - One of the best experts on this subject based on the ideXlab platform.
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a systems biology pipeline identifies regulatory networks for stem Cell Engineering
Nature Biotechnology, 2019Co-Authors: Melissa A Kinney, Linda T Vo, Jenna M Frame, Jessica BarraganAbstract:A major challenge for stem Cell Engineering is achieving a holistic understanding of the molecular networks and biological processes governing Cell differentiation. To address this challenge, we describe a computational approach that combines gene expression analysis, previous knowledge from proteomic pathway informatics and Cell signaling models to delineate key transitional states of differentiating Cells at high resolution. Our network models connect sparse gene signatures with corresponding, yet disparate, biological processes to uncover molecular mechanisms governing Cell fate transitions. This approach builds on our earlier CellNet and recent trajectory-defining algorithms, as illustrated by our analysis of hematopoietic specification along the erythroid lineage, which reveals a role for the EGF receptor family member, ErbB4, as an important mediator of blood development. We experimentally validate this prediction and perturb the pathway to improve erythroid maturation from human pluripotent stem Cells. These results exploit an integrative systems perspective to identify new regulatory processes and nodes useful in Cell Engineering. An advanced CellNet pipeline models the dynamics of stem Cell differentiation.
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A systems biology pipeline identifies regulatory networks for stem Cell Engineering.
Nature Biotechnology, 2019Co-Authors: Melissa A Kinney, Linda T Vo, Jenna M Frame, Jessica Barragan, Ashlee J. Conway, Shuai Li, Kwok-kin Wong, James J. Collins, Patrick Cahan, Trista E. NorthAbstract:A major challenge for stem Cell Engineering is achieving a holistic understanding of the molecular networks and biological processes governing Cell differentiation. To address this challenge, we describe a computational approach that combines gene expression analysis, previous knowledge from proteomic pathway informatics and Cell signaling models to delineate key transitional states of differentiating Cells at high resolution. Our network models connect sparse gene signatures with corresponding, yet disparate, biological processes to uncover molecular mechanisms governing Cell fate transitions. This approach builds on our earlier CellNet and recent trajectory-defining algorithms, as illustrated by our analysis of hematopoietic specification along the erythroid lineage, which reveals a role for the EGF receptor family member, ErbB4, as an important mediator of blood development. We experimentally validate this prediction and perturb the pathway to improve erythroid maturation from human pluripotent stem Cells. These results exploit an integrative systems perspective to identify new regulatory processes and nodes useful in Cell Engineering.
Jessica Barragan - One of the best experts on this subject based on the ideXlab platform.
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a systems biology pipeline identifies regulatory networks for stem Cell Engineering
Nature Biotechnology, 2019Co-Authors: Melissa A Kinney, Linda T Vo, Jenna M Frame, Jessica BarraganAbstract:A major challenge for stem Cell Engineering is achieving a holistic understanding of the molecular networks and biological processes governing Cell differentiation. To address this challenge, we describe a computational approach that combines gene expression analysis, previous knowledge from proteomic pathway informatics and Cell signaling models to delineate key transitional states of differentiating Cells at high resolution. Our network models connect sparse gene signatures with corresponding, yet disparate, biological processes to uncover molecular mechanisms governing Cell fate transitions. This approach builds on our earlier CellNet and recent trajectory-defining algorithms, as illustrated by our analysis of hematopoietic specification along the erythroid lineage, which reveals a role for the EGF receptor family member, ErbB4, as an important mediator of blood development. We experimentally validate this prediction and perturb the pathway to improve erythroid maturation from human pluripotent stem Cells. These results exploit an integrative systems perspective to identify new regulatory processes and nodes useful in Cell Engineering. An advanced CellNet pipeline models the dynamics of stem Cell differentiation.
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A systems biology pipeline identifies regulatory networks for stem Cell Engineering.
Nature Biotechnology, 2019Co-Authors: Melissa A Kinney, Linda T Vo, Jenna M Frame, Jessica Barragan, Ashlee J. Conway, Shuai Li, Kwok-kin Wong, James J. Collins, Patrick Cahan, Trista E. NorthAbstract:A major challenge for stem Cell Engineering is achieving a holistic understanding of the molecular networks and biological processes governing Cell differentiation. To address this challenge, we describe a computational approach that combines gene expression analysis, previous knowledge from proteomic pathway informatics and Cell signaling models to delineate key transitional states of differentiating Cells at high resolution. Our network models connect sparse gene signatures with corresponding, yet disparate, biological processes to uncover molecular mechanisms governing Cell fate transitions. This approach builds on our earlier CellNet and recent trajectory-defining algorithms, as illustrated by our analysis of hematopoietic specification along the erythroid lineage, which reveals a role for the EGF receptor family member, ErbB4, as an important mediator of blood development. We experimentally validate this prediction and perturb the pathway to improve erythroid maturation from human pluripotent stem Cells. These results exploit an integrative systems perspective to identify new regulatory processes and nodes useful in Cell Engineering.
Jenna M Frame - One of the best experts on this subject based on the ideXlab platform.
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a systems biology pipeline identifies regulatory networks for stem Cell Engineering
Nature Biotechnology, 2019Co-Authors: Melissa A Kinney, Linda T Vo, Jenna M Frame, Jessica BarraganAbstract:A major challenge for stem Cell Engineering is achieving a holistic understanding of the molecular networks and biological processes governing Cell differentiation. To address this challenge, we describe a computational approach that combines gene expression analysis, previous knowledge from proteomic pathway informatics and Cell signaling models to delineate key transitional states of differentiating Cells at high resolution. Our network models connect sparse gene signatures with corresponding, yet disparate, biological processes to uncover molecular mechanisms governing Cell fate transitions. This approach builds on our earlier CellNet and recent trajectory-defining algorithms, as illustrated by our analysis of hematopoietic specification along the erythroid lineage, which reveals a role for the EGF receptor family member, ErbB4, as an important mediator of blood development. We experimentally validate this prediction and perturb the pathway to improve erythroid maturation from human pluripotent stem Cells. These results exploit an integrative systems perspective to identify new regulatory processes and nodes useful in Cell Engineering. An advanced CellNet pipeline models the dynamics of stem Cell differentiation.
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A systems biology pipeline identifies regulatory networks for stem Cell Engineering.
Nature Biotechnology, 2019Co-Authors: Melissa A Kinney, Linda T Vo, Jenna M Frame, Jessica Barragan, Ashlee J. Conway, Shuai Li, Kwok-kin Wong, James J. Collins, Patrick Cahan, Trista E. NorthAbstract:A major challenge for stem Cell Engineering is achieving a holistic understanding of the molecular networks and biological processes governing Cell differentiation. To address this challenge, we describe a computational approach that combines gene expression analysis, previous knowledge from proteomic pathway informatics and Cell signaling models to delineate key transitional states of differentiating Cells at high resolution. Our network models connect sparse gene signatures with corresponding, yet disparate, biological processes to uncover molecular mechanisms governing Cell fate transitions. This approach builds on our earlier CellNet and recent trajectory-defining algorithms, as illustrated by our analysis of hematopoietic specification along the erythroid lineage, which reveals a role for the EGF receptor family member, ErbB4, as an important mediator of blood development. We experimentally validate this prediction and perturb the pathway to improve erythroid maturation from human pluripotent stem Cells. These results exploit an integrative systems perspective to identify new regulatory processes and nodes useful in Cell Engineering.
Linda T Vo - One of the best experts on this subject based on the ideXlab platform.
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a systems biology pipeline identifies regulatory networks for stem Cell Engineering
Nature Biotechnology, 2019Co-Authors: Melissa A Kinney, Linda T Vo, Jenna M Frame, Jessica BarraganAbstract:A major challenge for stem Cell Engineering is achieving a holistic understanding of the molecular networks and biological processes governing Cell differentiation. To address this challenge, we describe a computational approach that combines gene expression analysis, previous knowledge from proteomic pathway informatics and Cell signaling models to delineate key transitional states of differentiating Cells at high resolution. Our network models connect sparse gene signatures with corresponding, yet disparate, biological processes to uncover molecular mechanisms governing Cell fate transitions. This approach builds on our earlier CellNet and recent trajectory-defining algorithms, as illustrated by our analysis of hematopoietic specification along the erythroid lineage, which reveals a role for the EGF receptor family member, ErbB4, as an important mediator of blood development. We experimentally validate this prediction and perturb the pathway to improve erythroid maturation from human pluripotent stem Cells. These results exploit an integrative systems perspective to identify new regulatory processes and nodes useful in Cell Engineering. An advanced CellNet pipeline models the dynamics of stem Cell differentiation.
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A systems biology pipeline identifies regulatory networks for stem Cell Engineering.
Nature Biotechnology, 2019Co-Authors: Melissa A Kinney, Linda T Vo, Jenna M Frame, Jessica Barragan, Ashlee J. Conway, Shuai Li, Kwok-kin Wong, James J. Collins, Patrick Cahan, Trista E. NorthAbstract:A major challenge for stem Cell Engineering is achieving a holistic understanding of the molecular networks and biological processes governing Cell differentiation. To address this challenge, we describe a computational approach that combines gene expression analysis, previous knowledge from proteomic pathway informatics and Cell signaling models to delineate key transitional states of differentiating Cells at high resolution. Our network models connect sparse gene signatures with corresponding, yet disparate, biological processes to uncover molecular mechanisms governing Cell fate transitions. This approach builds on our earlier CellNet and recent trajectory-defining algorithms, as illustrated by our analysis of hematopoietic specification along the erythroid lineage, which reveals a role for the EGF receptor family member, ErbB4, as an important mediator of blood development. We experimentally validate this prediction and perturb the pathway to improve erythroid maturation from human pluripotent stem Cells. These results exploit an integrative systems perspective to identify new regulatory processes and nodes useful in Cell Engineering.
Michel Sadelain - One of the best experts on this subject based on the ideXlab platform.
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therapeutic t Cell Engineering
Nature, 2017Co-Authors: Michel Sadelain, Isabelle Riviere, Stanley R RiddellAbstract:Genetically engineered T Cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B Cell malignancies. Engineered T Cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape. Advances in the selection of optimal T Cells, genetic Engineering, and Cell manufacturing are poised to broaden T-Cell-based therapies and foster new applications in infectious diseases and autoimmunity. The use of genetically engineered T Cells in the treatment of cancer is reviewed, with particular focus on anti-CD19 chimaeric antigen receptor therapy, providing a summary of past progress and current status, and potential future directions. Michel Sadelain and colleagues review the use of genetically engineered T Cells in the treatment of patients with cancer. They focus in particular on anti-CD19 chimaeric antigen receptor (CAR)-modified T Cell therapy for leukaemia and lymphoma, providing a summary of past progress and current status, and discuss potential future directions encompassing solid tumours.
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New Cell Sources for T Cell Engineering and Adoptive Immunotherapy
Cell Stem Cell, 2015Co-Authors: Maria Themeli, Isabelle Riviere, Michel SadelainAbstract:The promising clinical results obtained with engineered T Cells, including chimeric antigen receptor (CAR) therapy, call for further advancements to facilitate and broaden their applicability. One potentially beneficial innovation is to exploit new T Cell sources that reduce the need for autologous Cell manufacturing and enable Cell transfer across histocompatibility barriers. Here we review emerging T Cell Engineering approaches that utilize alternative T Cell sources, which include virus-specific or T Cell receptor-less allogeneic T Cells, expanded lymphoid progenitors, and induced pluripotent stem Cell (iPSC)-derived T lymphocytes. The latter offer the prospect for true off-the-shelf, genetically enhanced, histocompatible Cell therapy products.
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Hematopoietic stem Cell Engineering at a crossroads.
Blood, 2011Co-Authors: Isabelle Riviere, Cynthia E. Dunbar, Michel SadelainAbstract:The genetic Engineering of hematopoietic stem Cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem Cell Engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem Cells, herald the advent of safer and more effective hematopoietic stem Cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead.
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Stem Cell Engineering for the treatment of severe hemoglobinopathies.
Current Molecular Medicine, 2008Co-Authors: Michel Sadelain, Farid Boulad, Leszek Lisowki, Isabelle RiviereAbstract:The s-thalassemias and sickle Cell anemia are severe congenital anemias for which there is presently no curative therapy other than allogeneic bone marrow transplantation. This therapeutic option, however, is not available to most patients due to the lack of an HLA-matched bone marrow donor. Emerging modalities based on Cell Engineering offer new prospects for potentially curative approaches that are applicable to more patients. The first is based on the transfer of a regulated globin gene in autologous hematopoietic stem Cells (HSCs). This strategy, simple in principle, raises major challenges in terms of controlling transgene expression, which ideally should be erythroid-specific, differentiation and stage-restricted, elevated, position-independent, and sustained over time. Following the original report by May et al., several groups have reported that lentiviral vectors encoding slightly different combinations of proximal and distal transcriptional control elements of the normal human s-globin gene permit lineage-specific and elevated s-globin expression in vivo, resulting in therapeutic hemoglobin production and correction of anemia in s-thalassemic mice. Clinical studies utilizing the TNS.3 vector are likely to be initiated in the US in 2009. While the addition of the wild-type s-globin gene is naturally suited for treating s-thalassemia, several alternatives have been proposed for the treatment of sickle Cell disease, using either γ- or mutant s-globin gene addition, trans-splicing or RNA interference. The recent discovery that adult somatic Cells can be reprogrammed to become pluripotent stem Cells from which HSCs can be derived, provides yet another venue for developing stem Cell Engineering using either lentiviral vectors or homologous recombination techniques. Altogether, these recent advances bode well for the advent of curative stem Cell-based therapies.