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Han, Simeng

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Han

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Simeng

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Han, Simeng
Author's Publications: search.filters.isAuthorOfPublication.15298c4f-4190-4b26-bb9d-ca75fea8d37d

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    Statistical Methods for Aggregation of Indirect Information
    (2014-06-06) Han, Simeng; Liu, Jun; Harrington, David; Wei, Lee-Jen
    How to properly aggregate indirect information is more and more important. In this dissertation, we will present two aspects of the issue: indirect comparison of treatment effects and aggregation of ordered-based rank data.
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    NF2/Merlin Is a Novel Negative Regulator of mTOR Complex 1, and Activation of mTORC1 Is Associated with Meningioma and Schwannoma Growth
    (American Society for Microbiology, 2009) James, Marianne F.; Han, Simeng; Polizzano, Carolyn; Plotkin, Scott; Manning, Brendan; Stemmer-Rachamimov, Anat; Gusella, James; Ramesh, Vijaya
    Inactivating mutations of the neurofibromatosis 2 (NF2) gene, NF2, result predominantly in benign neurological tumors, schwannomas and meningiomas, in humans; however, mutations in murine Nf2 lead to a broad spectrum of cancerous tumors. The tumor-suppressive function of the NF2 protein, merlin, a membrane-cytoskeleton linker, remains unclear. Here, we identify the mammalian target of rapamycin complex 1 (mTORC1) as a novel mediator of merlin's tumor suppressor activity. Merlin-deficient human meningioma cells and merlin knockdown arachnoidal cells, the nonneoplastic cell counterparts of meningiomas, exhibit rapamycin-sensitive constitutive mTORC1 activation and increased growth. NF2 patient tumors and Nf2-deficient mouse embryonic fibroblasts demonstrate elevated mTORC1 signaling. Conversely, the exogenous expression of wild-type merlin isoforms, but not a patient-derived L64P mutant, suppresses mTORC1 signaling. Merlin does not regulate mTORC1 via the established mechanism of phosphoinositide 3-kinase-Akt or mitogen-activated protein kinase/extracellular signal-regulated kinase-mediated TSC2 inactivation and may instead regulate TSC/mTOR signaling in a novel fashion. In conclusion, the deregulation of mTORC1 activation underlies the aberrant growth and proliferation of NF2-associated tumors and may restrain the growth of these lesions through negative feedback mechanisms, suggesting that rapamycin in combination with phosphoinositide 3-kinase inhibitors may be therapeutic for NF2.