Neuroblastoma is a common childhood tumor that arises from the peripheral neural crest. Maximal s... more Neuroblastoma is a common childhood tumor that arises from the peripheral neural crest. Maximal surgery, chemotherapy, radiation therapy and bone marrow replacement are often not sufficient to save the lives of the 60% of children with neuroblastoma whose disease has already disseminated at the time of their initial diagnoses. Development of novel therapeutic approaches for neuroblastoma is dependent upon in vitro and in vivo model systems in which to pilot such therapies. Cell culture models, primary cultures of human neuroblastomas, and in vivo animal models make possible the preclinical development of new approaches to this tumor.Kathryn Albers – University of Pittsburgh, Pittsburgh, USA
The National Institute of Neurological Disorders and Stroke (NINDS) held a workshop entitled, &qu... more The National Institute of Neurological Disorders and Stroke (NINDS) held a workshop entitled, "Next Generation Strategies for Gene-Targeted Therapies of Central Nervous System (CNS) Disorders" in September 2019 in Bethesda, Maryland. The meeting brought together a multi-disciplinary group of experts in the field of CNS-directed gene-targeted therapy delivery from academia, industry, advocacy, and the government. The group was charged with identifying the key challenges and gaps in this evolving field, as well as suggesting potential solutions. The workshop was divided into four sessions: (1) Control of Level and Location; (2) Improving Delivery and Distribution; (3) Enhancing Models and Manufacturing; and (4) Impacting Patients. Prior to the workshop, NINDS established working groups of key opinion leaders (KOLs) for each session. In pre-meeting teleconferences, KOLs were tasked with identifying the research gaps and key obstacles that delay and/or prevent gene-targeted therapies to move into the clinic. This approach allowed for the workshop to begin with problem-solving discussions and strategy development as the key issues had been established. The overall purpose of the workshop was to consider knowledge gaps and potential strategies to inform the community around CNS gene-targeted therapies, including but not limited to researchers and funders.
Our understanding of the mechanisms of cell death is ever evolving. Once thought to be a random, ... more Our understanding of the mechanisms of cell death is ever evolving. Once thought to be a random, passive process, cell death can be energy-requiring, orderly, and critically important for proper development of the nervous system. Two major pathways to cell death have been recognized and characterized.
High-risk neuroblastoma is a lethal childhood tumor characterized by increased oncoprotein MYCN e... more High-risk neuroblastoma is a lethal childhood tumor characterized by increased oncoprotein MYCN expression. As strategies for modulation of MYCN function itself have proved challenging, targeting of MYCN's downstream effectors may provide an alternative option. Protein arginine methyltransferase 1 (PRMT1) has been reported as a MYCN target gene in neuroblastoma; high expression of PRMT1 is significantly associated with a poor prognosis. Importantly, PRMT1-deficient cells have been shown to be hypersensitive to chemotherapy-induced DNA damage, suggesting that targeting PRMT1 may overcome drug resistance for patients with advanced neuroblastoma. However, the underlying mechanisms of how PRMT1 contributes to chemoresistance and tumor progression are still largely unknown. We report here that PRMT1 forms a novel complex with EYA1, a phosphatase and transcriptional coactivator that may serve as the crucial determinant of survival versus apoptotic responses to DNA damage through dephosphorylation of histones. Interestingly, we found that EYA1 is highly expressed in advanced neuroblastoma and that PRMT1 physically associates with EYA1 through direct interaction. Further, rendering EYA1 refractory to methylation by PRMT1 abolishes its phosphatase activity. These findings suggest that PRMT1 methylase, EYA1 phosphatase, and PRMT1-EYA1 may be druggable targets for the therapy of neuroblastoma. Citation Format: Xingguo Li, Simeng Wang, Nina F. Schor. Methylase meets phosphatase: roles of PRMT and EYA1 in neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 464. doi:10.1158/1538-7445.AM2014-464
At the end of 2020, the National Institute of Neurological Disorders and Stroke, an institute of ... more At the end of 2020, the National Institute of Neurological Disorders and Stroke, an institute of the NIH, completed an 18-month-long strategic planning process that involved and engaged diverse internal and external biomedical and general stakeholders. The institute published and disseminated its 2021–2026 Strategic Plan online in December 2020. Now, 1 year into its implementation, this progress report presents accomplishments to date, new initiatives and opportunities, and a preview of the metrics and benchmarks we will use to gauge the future progress of the strategic plan's implementation.
The lupus anticoagulant has been theoretically linked with cerebrovascular dysfunction. All previ... more The lupus anticoagulant has been theoretically linked with cerebrovascular dysfunction. All previously described patients, however, have had other concomitant conditions known to predispose them to stroke. The patient described herein demonstrates the association of a lupuslike anticoagulant with thrombotic vascular occlusion in the central nervous system in the absence of other causes of vasculopathy.
Neuroblastoma is a common childhood tumor that arises from the peripheral neural crest. Maximal s... more Neuroblastoma is a common childhood tumor that arises from the peripheral neural crest. Maximal surgery, chemotherapy, radiation therapy and bone marrow replacement are often not sufficient to save the lives of the 60% of children with neuroblastoma whose disease has already disseminated at the time of their initial diagnoses. Development of novel therapeutic approaches for neuroblastoma is dependent upon in vitro and in vivo model systems in which to pilot such therapies. Cell culture models, primary cultures of human neuroblastomas, and in vivo animal models make possible the preclinical development of new approaches to this tumor.Kathryn Albers – University of Pittsburgh, Pittsburgh, USA
The National Institute of Neurological Disorders and Stroke (NINDS) held a workshop entitled, &qu... more The National Institute of Neurological Disorders and Stroke (NINDS) held a workshop entitled, "Next Generation Strategies for Gene-Targeted Therapies of Central Nervous System (CNS) Disorders" in September 2019 in Bethesda, Maryland. The meeting brought together a multi-disciplinary group of experts in the field of CNS-directed gene-targeted therapy delivery from academia, industry, advocacy, and the government. The group was charged with identifying the key challenges and gaps in this evolving field, as well as suggesting potential solutions. The workshop was divided into four sessions: (1) Control of Level and Location; (2) Improving Delivery and Distribution; (3) Enhancing Models and Manufacturing; and (4) Impacting Patients. Prior to the workshop, NINDS established working groups of key opinion leaders (KOLs) for each session. In pre-meeting teleconferences, KOLs were tasked with identifying the research gaps and key obstacles that delay and/or prevent gene-targeted therapies to move into the clinic. This approach allowed for the workshop to begin with problem-solving discussions and strategy development as the key issues had been established. The overall purpose of the workshop was to consider knowledge gaps and potential strategies to inform the community around CNS gene-targeted therapies, including but not limited to researchers and funders.
Our understanding of the mechanisms of cell death is ever evolving. Once thought to be a random, ... more Our understanding of the mechanisms of cell death is ever evolving. Once thought to be a random, passive process, cell death can be energy-requiring, orderly, and critically important for proper development of the nervous system. Two major pathways to cell death have been recognized and characterized.
High-risk neuroblastoma is a lethal childhood tumor characterized by increased oncoprotein MYCN e... more High-risk neuroblastoma is a lethal childhood tumor characterized by increased oncoprotein MYCN expression. As strategies for modulation of MYCN function itself have proved challenging, targeting of MYCN's downstream effectors may provide an alternative option. Protein arginine methyltransferase 1 (PRMT1) has been reported as a MYCN target gene in neuroblastoma; high expression of PRMT1 is significantly associated with a poor prognosis. Importantly, PRMT1-deficient cells have been shown to be hypersensitive to chemotherapy-induced DNA damage, suggesting that targeting PRMT1 may overcome drug resistance for patients with advanced neuroblastoma. However, the underlying mechanisms of how PRMT1 contributes to chemoresistance and tumor progression are still largely unknown. We report here that PRMT1 forms a novel complex with EYA1, a phosphatase and transcriptional coactivator that may serve as the crucial determinant of survival versus apoptotic responses to DNA damage through dephosphorylation of histones. Interestingly, we found that EYA1 is highly expressed in advanced neuroblastoma and that PRMT1 physically associates with EYA1 through direct interaction. Further, rendering EYA1 refractory to methylation by PRMT1 abolishes its phosphatase activity. These findings suggest that PRMT1 methylase, EYA1 phosphatase, and PRMT1-EYA1 may be druggable targets for the therapy of neuroblastoma. Citation Format: Xingguo Li, Simeng Wang, Nina F. Schor. Methylase meets phosphatase: roles of PRMT and EYA1 in neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 464. doi:10.1158/1538-7445.AM2014-464
At the end of 2020, the National Institute of Neurological Disorders and Stroke, an institute of ... more At the end of 2020, the National Institute of Neurological Disorders and Stroke, an institute of the NIH, completed an 18-month-long strategic planning process that involved and engaged diverse internal and external biomedical and general stakeholders. The institute published and disseminated its 2021–2026 Strategic Plan online in December 2020. Now, 1 year into its implementation, this progress report presents accomplishments to date, new initiatives and opportunities, and a preview of the metrics and benchmarks we will use to gauge the future progress of the strategic plan's implementation.
The lupus anticoagulant has been theoretically linked with cerebrovascular dysfunction. All previ... more The lupus anticoagulant has been theoretically linked with cerebrovascular dysfunction. All previously described patients, however, have had other concomitant conditions known to predispose them to stroke. The patient described herein demonstrates the association of a lupuslike anticoagulant with thrombotic vascular occlusion in the central nervous system in the absence of other causes of vasculopathy.
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Papers by Nina Schor