19 results on '"Weissman, Irving L."'
Search Results
2. Plasticity of Adult Stem Cells
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Wagers, Amy J. and Weissman, Irving L.
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STEM cells , *MAMMALS , *TISSUES , *REGENERATION (Biology) - Abstract
Recent years have seen much excitement over the possibility that adult mammalian stem cells may be capable of differentiating across tissue lineage boundaries, and as such may represent novel, accessible, and very versatile effectors of therapeutic tissue regeneration. Yet studies proposing such “plasticity” of adult somatic stem cells remain controversial, and in general, existing evidence suggests that in vivo such unexpected transformations are exceedingly rare and in some cases can be accounted for by equally unexpected alternative explanations. [Copyright &y& Elsevier]
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- 2004
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3. Stem cells: Units of development, units of regeneration, and units in evolution.
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Weissman, Irving L.
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STEM cells , *CYTOLOGICAL research - Abstract
Discusses the history and advances in stem cells research. Examination of hematopoietic stem cells; Regeneration of the hematolymphoid system; Progeny of cell divisions; Development processes associated with stem and progenitor cells.
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- 2000
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4. Identification of clonogenic common lymphoid progenitors on mouse bone marrow.
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Kondo, Motonari and Weissman, Irving L.
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BONE cells , *HEMATOPOIETIC system - Abstract
Presents a study which identified clonogenic common lymphoid progenitors (CLP) in mouse bone marrow. Outline of the contents of adult bone marrow; What constitutes a space in the hematopoietic lineage maps; Examination of whether CLPs exist in sites of early lymphopoiesis at a clonal level; Identification of the Lin-IL-7R+Thy-1.1-Sca-1...c-Kit... population.
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- 1997
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5. Enforced expression of Bcl-2 in monocytes rescues macrophages and partially reverses...
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Lagasse, Eric and Weissman, Irving L.
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MONOCYTES , *MACROPHAGES , *OSTEOPETROSIS - Abstract
Suggests that the enforced express of Bcl-2 in monocytes rescues macrophages and partially reserves osteopetrosis in op/op mice according to a study. What osteopetrotic mice lack; Type of mice prepared for study; Findings of the study; Indepth look at study.
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- 1997
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6. Developmental switches in the immune system.
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Weissman, Irving L.
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IMMUNE system , *MOLECULAR immunology , *LYMPHOID tissue - Abstract
Discusses the internal mechanisms that trigger developmental switches in the immune system. Change in state of cells from one quantal stage to another; Role of lymphoid organs in morphological changes during an immune response; Lymphocyte homing receptors; Hematopoietic stem cells; Heterogeneity of stem cells during ontogeny.
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- 1994
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7. Pten, Tumorigenesis, and Stem Cell Self-Renewal
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Rossi, Derrick J. and Weissman, Irving L.
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CANCER treatment , *TUMOR suppressor proteins , *STEM cells , *CARCINOGENESIS - Abstract
Self-renewal pathways crucial for maintaining stem cells are deregulated in cancer, raising the spectre that cancer therapies targeting such pathways might also ablate normal stem cells. As report in a recent Nature paper, this may not be the case for the tumor suppressor protein Pten, which drives the self-renewal of normal hematopoietic stem cells and the formation of leukemia cells through different mechanisms. [Copyright &y& Elsevier]
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- 2006
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8. Differential Contribution of Chemotaxis and Substrate Restriction to Segregation of Immature and Mature Thymocytes
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Ehrlich, Lauren I. Richie, Oh, David Y., Weissman, Irving L., and Lewis, Richard S.
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CHEMOTAXIS , *T cells , *THYMUS physiology , *PERTUSSIS toxin , *CELL migration , *MICROSCOPICAL technique - Abstract
Summary: T cell development requires sequential localization of thymocyte subsets to distinct thymic microenvironments. To address mechanisms governing this segregation, we used two-photon microscopy to visualize migration of purified thymocyte subsets in defined microenvironments within thymic slices. Double-negative (CD4−8−) and double-positive (CD4+8+) thymocytes were confined to cortex where they moved slowly without directional bias. DP cells accumulated and migrated more rapidly in a specialized inner-cortical microenvironment, but were unable to migrate on medullary substrates. In contrast, CD4 single positive (SP) thymocytes migrated directionally toward the medulla, where they accumulated and moved very rapidly. Our results revealed a requisite two-step process governing CD4 SP cell medullary localization: the chemokine receptor CCR7 mediated chemotaxis of CD4 SP cells towards medulla, whereas a distinct pertussis-toxin sensitive pathway was required for medullary entry. These findings suggest that developmentally regulated responses to both chemotactic signals and specific migratory substrates guide thymocytes to specific locations in the thymus. [Copyright &y& Elsevier]
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- 2009
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9. Stems Cells and the Pathways to Aging and Cancer
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Rossi, Derrick J., Jamieson, Catriona H.M., and Weissman, Irving L.
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STEM cells , *PLANT diseases , *AGING , *DEVELOPMENTAL biology - Abstract
The aging of tissue-specific stem cell and progenitor cell compartments is believed to be central to the decline of tissue and organ integrity and function in the elderly. Here, we examine evidence linking stem cell dysfunction to the pathophysiological conditions accompanying aging, focusing on the mechanisms underlying stem cell decline and their contribution to disease pathogenesis. [Copyright &y& Elsevier]
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- 2008
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10. Stem Cells Are Units of Natural Selection in a Colonial Ascidian
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Laird, Diana J., De Tomaso, Anthony W., and Weissman, Irving L.
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STEM cells , *SEA squirts , *NATURAL selection , *GENETICS - Abstract
Summary: Stem cells are highly conserved biological units of development and regeneration. Here we formally demonstrate that stem cell lineages are also legitimate units of natural selection. In a colonial ascidian, Botryllus schlosseri, vascular fusion between genetically distinct individuals results in cellular parasitism of somatic tissues, gametes, or both. We show that genetic hierarchies of somatic and gametic parasitism following fusion can be replicated by transplanting cells between colonies. We prospectively isolate a population of multipotent, self-renewing stem cells that retain their competitive phenotype upon transplantation. Their single-cell contribution to either somatic or germline fates, but not to both, is consistent with separate lineages of somatic and germline stem cells or pluripotent stem cells that differentiate according to the niche in which they land. Since fusion is restricted to individuals that share a fusion/histocompatibility allele, these data suggest that histocompatibility genes in Botryllus evolved to protect the body from parasitic stem cells usurping asexual or sexual inheritance. [Copyright &y& Elsevier]
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- 2005
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11. JunB Deficiency Leads to a Myeloproliferative Disorder Arising from Hematopoietic Stem Cells
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Passegué, Emmanuelle, Wagner, Erwin F., and Weissman, Irving L.
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PROTEINS , *LEUKEMIA , *CANCER , *MACROPHAGES - Abstract
The AP-1 transcription factor JunB is a transcriptional regulator of myelopoiesis. Inactivation of JunB in postnatal mice results in a myeloproliferative disorder (MPD) resembling early human chronic myelogenous leukemia (CML). Here, we show that JunB regulates the numbers of hematopoietic stem cells (HSC). JunB overexpression decreases the frequency of long-term HSC (LT-HSC), while JunB inactivation specifically expands the numbers of LT-HSC and granulocyte/macrophage progenitors (GMP) resulting in chronic MPD. Further, we demonstrate that junB inactivation must take place in LT-HSC, and not at later stages of myelopoiesis, to induce MPD and that only junB-deficient LT-HSC are capable of transplanting the MPD to recipient mice. These results demonstrate a stem cell-specific role for JunB in normal and leukemic hematopoiesis and provide experimental evidence that leukemic stem cells (LSC) can reside at the LT-HSC stage of development in a mouse model of MPD. [Copyright &y& Elsevier]
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- 2004
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12. Purification and characterization of human neural stem and progenitor cells.
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Liu, Daniel Dan, He, Joy Q., Sinha, Rahul, Eastman, Anna E., Toland, Angus M., Morri, Maurizio, Neff, Norma F., Vogel, Hannes, Uchida, Nobuko, and Weissman, Irving L.
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NEURAL stem cells , *PROGENITOR cells , *NEUROGLIA , *FETAL brain , *ASTROCYTES , *DEVELOPMENTAL neurobiology , *OLIGODENDROGLIA , *NEURONS - Abstract
The human brain undergoes rapid development at mid-gestation from a pool of neural stem and progenitor cells (NSPCs) that give rise to the neurons, oligodendrocytes, and astrocytes of the mature brain. Functional study of these cell types has been hampered by a lack of precise purification methods. We describe a method for prospectively isolating ten distinct NSPC types from the developing human brain using cell-surface markers. CD24−THY1−/lo cells were enriched for radial glia, which robustly engrafted and differentiated into all three neural lineages in the mouse brain. THY1hi cells marked unipotent oligodendrocyte precursors committed to an oligodendroglial fate, and CD24+THY1−/lo cells marked committed excitatory and inhibitory neuronal lineages. Notably, we identify and functionally characterize a transcriptomically distinct THY1hiEGFRhiPDGFRA− bipotent glial progenitor cell (GPC), which is lineage-restricted to astrocytes and oligodendrocytes, but not to neurons. Our study provides a framework for the functional study of distinct cell types in human neurodevelopment. [Display omitted] • Purification, functional validation of 10 NSPC types in human neurodevelopment • Index-sorting maps transcriptome onto immunophenotype to derive a gating strategy • Identification of transcriptomically, functionally defined glial progenitor cell (GPC) • GPCs likely arise from oRG, giving rise to oligodendrocytes/astrocytes but not neurons A framework for the prospective isolation of neural stem and progenitor cells from the developing human brain is provided to facilitate the functional study of distinct cell types in human neurodevelopment. [ABSTRACT FROM AUTHOR]
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- 2023
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13. Stem Cells Are Units of Natural Selection in a Colonial Ascidian
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Laird, Diana J., De Tomaso, Anthony W., and Weissman, Irving L.
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- 2006
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14. Tuning Cytokine Receptor Signaling by Re-orienting Dimer Geometry with Surrogate Ligands.
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Moraga, Ignacio, Wernig, Gerlinde, Wilmes, Stephan, Gryshkova, Vitalina, Richter, Christian P., Hong, Wan-Jen, Sinha, Rahul, Guo, Feng, Fabionar, Hyna, Wehrman, Tom S., Krutzik, Peter, Demharter, Samuel, Plo, Isabelle, Weissman, Irving L., Minary, Peter, Majeti, Ravindra, Constantinescu, Stefan N., Piehler, Jacob, and Garcia, K. Christopher
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CELL membranes , *CYTOKINES , *GROWTH factors , *LIGANDS (Biochemistry) , *ERYTHROPOIETIN receptors , *CELLULAR signal transduction , *GENETIC regulation - Abstract
Summary Most cell-surface receptors for cytokines and growth factors signal as dimers, but it is unclear whether remodeling receptor dimer topology is a viable strategy to “tune” signaling output. We utilized diabodies (DA) as surrogate ligands in a prototypical dimeric receptor-ligand system, the cytokine Erythropoietin (EPO) and its receptor (EpoR), to dimerize EpoR ectodomains in non-native architectures. Diabody-induced signaling amplitudes varied from full to minimal agonism, and structures of these DA/EpoR complexes differed in EpoR dimer orientation and proximity. Diabodies also elicited biased or differential activation of signaling pathways and gene expression profiles compared to EPO. Non-signaling diabodies inhibited proliferation of erythroid precursors from patients with a myeloproliferative neoplasm due to a constitutively active JAK2V617F mutation. Thus, intracellular oncogenic mutations causing ligand-independent receptor activation can be counteracted by extracellular ligands that re-orient receptors into inactive dimer topologies. This approach has broad applications for tuning signaling output for many dimeric receptor systems. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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15. Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma
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Chao, Mark P., Alizadeh, Ash A., Tang, Chad, Myklebust, June H., Varghese, Bindu, Gill, Saar, Jan, Max, Cha, Adriel C., Chan, Charles K., Tan, Brent T., Park, Christopher Y., Zhao, Feifei, Kohrt, Holbrook E., Malumbres, Raquel, Briones, Javier, Gascoyne, Randy D., Lossos, Izidore S., Levy, Ronald, Weissman, Irving L., and Majeti, Ravindra
- Abstract
Summary: Monoclonal antibodies are standard therapeutics for several cancers including the anti-CD20 antibody rituximab for B cell non-Hodgkin lymphoma (NHL). Rituximab and other antibodies are not curative and must be combined with cytotoxic chemotherapy for clinical benefit. Here we report the eradication of human NHL solely with a monoclonal antibody therapy combining rituximab with a blocking anti-CD47 antibody. We identified increased expression of CD47 on human NHL cells and determined that higher CD47 expression independently predicted adverse clinical outcomes in multiple NHL subtypes. Blocking anti-CD47 antibodies preferentially enabled phagocytosis of NHL cells and synergized with rituximab. Treatment of human NHL-engrafted mice with anti-CD47 antibody reduced lymphoma burden and improved survival, while combination treatment with rituximab led to elimination of lymphoma and cure. These antibodies synergized through a mechanism combining Fc receptor (FcR)-dependent and FcR-independent stimulation of phagocytosis that might be applicable to many other cancers. [Copyright &y& Elsevier]
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- 2010
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16. New Evidence Supporting Megakaryocyte-Erythrocyte Potential of Flk2/Flt3+ Multipotent Hematopoietic Progenitors
- Author
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Forsberg, E. Camilla, Serwold, Thomas, Kogan, Scott, Weissman, Irving L., and Passegué, Emmanuelle
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HEMATOPOIETIC stem cells , *BLOOD cells , *BONE marrow cells , *STEM cells - Abstract
Summary: A model of hematopoietic development wherein multipotentiality is conserved until segregation of myeloid and lymphoid potential has recently been challenged, proposing that megakaryocyte/erythrocyte (MegE) potential is lost in Flk2/Flt3-expressing early progenitors. Here, we used sensitive in vivo approaches to quantitatively and kinetically assess the MegE potential of hematopoietic stem cells and various Flk2+ early progenitors and compared it with the MegE potential of downstream committed myeloid and lymphoid progenitors and with their ability to give rise to mature myelomonocytic and lymphoid cells. We demonstrate that Flk2+ early progenitors retain MegE potential in vivo both at the population and clonal levels. These results indicate that Flk2 expression by early progenitors is not at the expense of full multipotency and support the current model of hematopoietic development with segregation of myeloid and lymphoid lineages from multipotent progenitors. [Copyright &y& Elsevier]
- Published
- 2006
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17. fester, a Candidate Allorecognition Receptor from a Primitive Chordate
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Nyholm, Spencer V., Passegue, Emmanuelle, Ludington, William B., Voskoboynik, Ayelet, Mitchel, Katrina, Weissman, Irving L., and De Tomaso, Anthony W.
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TRANSPLANTATION immunology , *IMMUNOGLOBULINS , *MOLECULAR cloning , *MONOCLONAL antibodies - Abstract
Summary: Histocompatibility in the primitive chordate, Botryllus schlosseri, is controlled by a single, highly polymorphic locus, the FuHC. By taking a forward genetic approach, we have identified a locus encoded near the FuHC, called fester, which is polymorphic, polygenic, and inherited in distinct haplotypes. Somatic diversification occurs through extensive alternative splicing, with each individual expressing a unique repertoire of splice forms, both membrane bound and potentially secreted, all expressed in tissues intimately associated with histocompatibility. Functional studies, via both siRNA-mediated knockdown and direct blocking by monoclonal antibodies raised against fester, were able to disrupt predicted histocompatibility outcomes. The genetic and somatic diversity, coupled to the expression and functional data, suggests that fester is a receptor involved in histocompatibility. [Copyright &y& Elsevier]
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- 2006
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18. Isolation of Adult Mouse Myogenic Progenitors: Functional Heterogeneity of Cells within and Engrafting Skeletal Muscle
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Sherwood, Richard I., Christensen, Julie L., Conboy, Irina M., Conboy, Michael J., Rando, Thomas A., Weissman, Irving L., and Wagers, Amy J.
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MUSCLES , *NEURONS , *IMMUNE system , *CELLS - Abstract
Skeletal muscle regeneration in adults is thought to occur through the action of myogenic satellite cells located in close association with mature muscle fibers; however, these precursor cells have not been prospectively isolated, and recent studies have suggested that additional muscle progenitors, including cells of bone marrow or hematopoietic origin, may exist. To clarify the origin(s) of adult myogenic cells, we used phenotypic, morphological, and functional criteria to identify and prospectively isolate a subset of myofiber-associated cells capable at the single cell level of generating myogenic colonies at high frequency. Importantly, although muscle-engrafted cells from marrow and/or circulation localized to the same anatomic compartment as myogenic satellite cells and expressed some though not all satellite cell markers, they displayed no intrinsic myogenicity. Together, these studies describe the clonal isolation of functional adult myogenic progenitors and demonstrate that these cells do not arise from hematopoietic or other bone marrow or circulating precursors. [Copyright &y& Elsevier]
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- 2004
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19. Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling.
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Ho, Chia Chi M., Chhabra, Akanksha, Starkl, Philipp, Schnorr, Peter-John, Wilmes, Stephan, Moraga, Ignacio, Kwon, Hye-Sook, Gaudenzio, Nicolas, Sibilano, Riccardo, Wehrman, Tom S., Gakovic, Milica, Sockolosky, Jonathan T., Tiffany, Matthew R., Ring, Aaron M., Piehler, Jacob, Weissman, Irving L., Galli, Stephen J., Shizuru, Judith A., and Garcia, K. Christopher
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GENETIC pleiotropy , *STEM cell factor , *DIMERIZATION , *MAST cells , *CELLULAR signal transduction , *HEMATOPOIETIC stem cells - Abstract
Summary Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion but can be toxic when administered in vivo because it concurrently activates mast cells. We engineered a mechanism-based SCF partial agonist that impaired c-Kit dimerization, truncating downstream signaling amplitude. This SCF variant elicited biased activation of hematopoietic progenitors over mast cells in vitro and in vivo. Mouse models of SCF-mediated anaphylaxis, radioprotection, and hematopoietic expansion revealed that this SCF partial agonist retained therapeutic efficacy while exhibiting virtually no anaphylactic off-target effects. The approach of biasing cell activation by tuning signaling thresholds and outputs has applications to many dimeric receptor-ligand systems. [ABSTRACT FROM AUTHOR]
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- 2017
- Full Text
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