方琰
1]麻醉学;2]量子生物学;3]纳米生物医药;4]生物电子学;5]学科交叉与综合前沿。
个性化签名
- 姓名:方琰
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
临床医学
- 研究兴趣:1]麻醉学;2]量子生物学;3]纳米生物医药;4]生物电子学;5]学科交叉与综合前沿。
方琰,麻醉执业医师、研究员、研究生导师。学历:1983年7月获医学学士学位,1990年7月获医学博士学位。医、教、研工作简历:1983年起从事临床麻醉,带教医学系本科生、进修医师、研究生和研究相关临床医学应用基础和学科交叉综合前沿问题。1992-1994年作为项目负责人主持并按期完成国家自然科学基金项目和国家自然科学基金国际合作研究项目(NSFC No.39100136 & NSFC No.39410120518)及其国际人类前沿科学项目(HFSP No.224-93)。1993年获得HFSP创新研究奖励。1994年7-10月以NSFC和HFSP客座研究员身份赴美国UMDNJ大学主持并按期完成中-美合作研究。1998-2001年作为课题负责人主持完成本单位中青年科研启动基金课题两项(专项A-25和A-27)。2001-2003年作为中方课题负责人主持完成科技部和教育部中-德学者科技合作项目(MOST-CNNCBD & BMBF-DLR:GCH 01/03、MOE & DFG Gz 224 CHV 112/36/02),其间(2003/04-05)以MOE & DFG客座教授身份赴德国国家于利希研究中心超薄膜和生物化学传感器研究所主持并按期完成中-德双边合作研究。2003-2005年作为课题负责人主持并按期完成上海市科学技术委员会基础处学科交叉与综合前沿重点课题“基因反馈调控的模拟与功能再现”(STC No.03JC14020)。目前作为负责人主持承担国家自然科学基金面上项目(NSFC No.30470409,2004-2007)和上海市纳米科技攻关课题(STC No. 0453nm0850,2004-2006)。目前所从事的研究领域是:1]麻醉学;2]量子生物学;3]纳米生物医药;4]生物电子学;5]学科交叉与综合前沿。创新研究成果:在创新药物领域,以独立发明人获得中国发明专利授权一项、2004-2005年间在纳米科技领域,获得中国发明专利受理三项并进入国际专利申请阶段;第一作者即通讯作者论文20余篇,其中SCI收录6篇,题录如下:
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419
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成果数
6
【期刊论文】ADMET Biosensors: Up-to-date Issues and Strategies
方琰, Yan Fang, AEFG, Andrease OffenhaeusserBCD
Med Sci Monit, 2004; 10 (12): MT127-132,-0001,():
-1年11月30日
This insight review introduces the new concepts, theories, technology, instruments, frontier issues, and key strategies of ADMET (absorption, distribution, metabolism, elimination, and toxicity) biosensors, from the fermi to the quantum levels. Information about ADMET, originating from one author's invention, a patented pharmacotherapy for rescuing cardio-cerebral vascular stunning and regulating vascular endothelial growth-factor signaling at the post-genomic level, can be detected by a new generation of ADMET biosensor. This is a single-cell/single-molecule fi eld-effect transistor (FET) hybrid system, where single molecules or single cells are assembled at the FET surface in a high density array manner via complementary metal-oxide-semiconductor (CMOS)-compatible technologies. Within a given nanometer distance, ADMET-mediated oxidation-reduction (redox) potentials, electrochemistry responses, and electron transfer processes can be simultaneously and directly probed by the gates of fi eld-effect transistor arrays. The nanometer details of the functional coupling principles and characterization technologies of DNA single-molecule/singlecell FETs, as well as the design of lab-on-a-chip instruments, are indicated. Four frontier issues and key strategies are elucidated in detail. This can lead to innovative technology for high-throughout screening of labs-on-chips to resolve the pharmaceutical industry's current bottleneck via novel, FET-based drug discovery and single-molecule/single-cell screening methods, which can bring about a pharmaceutical industry revolution in the 21st century.
drug discovery • lab-on-a chip medical technology
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【期刊论文】INTERACTIONS OF Na+, H2O2 AND THE Na+-Ca2+ EXCHANGER STIMULATE Ca2+ RELEASE IN CK1.4 CELLS
方琰, Yan Fang, * Mingyang Rang† and Lianfang He†
Chinical and Perimental Pharmacology and Physiology (1997) 24, 170-174,-0001,():
-1年11月30日
1. The present study aimed to demonstrate that interactions of cations hydrogen peroxied (H2O2) and the Na+-Ca2+ exchanger stimulate Ca2+ release and oscillations of cytosolic Ca2+[Ca2+]I in non-transfected Chinese Hamster Ovary (CHO) C1 cells and in transfected CHO (CK1.4) cells that contained an expression vector coding the Na+-Can2+ exchanger sequence. 2. The [45Ca2+] uptake assay, fura-2 fluorescence imaging and 2 2and 2 3 factorial orthogonal statistics provide compara-tive, direct, efficient, quantitative and transient methods to delineate the effects of such interactons on Ca2+ influx, Ca2+ release and [Ca2+]i in C1 and CK1.4 cells. 3. In contrast to the control of either Na2+-, Ca2+- or H2O2-free or C1 cells, ana elevated [45Ca2+] uptake was induced by Ca2+, Na+ and H2O2 individually and in combination, intra-cellular Ca2+ release was activated by H2O2 and by combinations of either H2O2 and Na+, H2O2 and the Na+-Ca2+ exchanger, Na+ and the Na+-Ca2+ exchanger or by H2O2, Na+ and the Na+-Ca2+ exchanger and a rise in [Ca2+]i was triggered by H2O2 Na+ and a combination of Na+ and the Na+-Ca2+ exchanger. 4. These results indicated that interactions between H2O2, Na+ and the Na+-Ca2+ exchanger stimulate intracellular Ca2+Na+ and the Na+-Ca2+ exchanger stimulate intracellular Ca2+ mobilization via Ca2+-induced Ca2+ release mechanisms, ATP-activated G-protein coupled P2y-purinoceptor-sensitive path-ways, Na+-Ca2+ exchanger-mediated Ca2+ influx and cation-π interaction (a strong non-covalent force between the cation and theπ face of an aromatic structure in the transmembrane protein). 5. The present findings, provide important clues for under-standing Ca2+ signal transduction mechanisms from the plasma membrane to the endoplasmic reticulum.
words, calcium metabolism,, cations,, freee radicals,, membrane protein physiology.,
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方琰, Y Fang, M Rang, L He, C Zhou
Biomed & Pharmacother 1998; 52; 145-56,-0001,():
-1年11月30日
Summary-Mode-actions of the Na+-Ca2+ exchanger from genes to mechanisms to a new strategy for brain disorders were comparatively s*udlea in oxidative stress, Io tran~femed Chinese hamster ovary (CHO) cells steadily expressing the Na+-Ca2+ exchanger's gone. Ca+-efflux via an active mode of the Na+-Ca2+ exchanger was elicited by hydrogen peroxide (H2O2) after preincubation of the cell with a Ca2+-free medium, whereas Ca2+-influx via a reverse mode of the Na+-Ca2+ exchanger was dramatically evoked by H2O2 after preincuhatlon of the cell with a Ca2+ medium, as a prelude to neuronal death. Accnrding to (45Ca2+) uptake of transfected CHO cells at given time inlervals or extracelluiar Na+[Na+]. gradients, hyperbola, logarithmic and sigmoid curve equations of the Na+-Ca2+ exchanger's mode-actions were respeetively defined in the absence and the presence of H2O2. The Na+-Ca2+ exchanger's eonfornational transition in oxidative stress was dominated by adenosine triphosphate (ATP)-dependent cytoskeletal redox modification, eation-π interactions and secondary Ca2+ activation These echanisms were used to generate an intracellularly distributed tetra-cluster (named VISA931) for rescuing G-protein agonist-sensitive signal transduetion and cortico-cerebral somatosensury evoke potential (SEP) from oxidation via activating forward o0eration of the Na+-Ca2+ exchanger, the β-adrenergic and the P2-purinergic receptors, bilking Ca2+ influx and catalyzing the dismutation ol superoxide anions (O2) to H2O2, In conclusion, knowledge-bascd drug design is a new strategy for developing promising candidates of neuroprotective agents
membrane proteins/, oxidative stress/, pharmaeology
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【期刊论文】Interaction of the Na+-Ca2+ exchanger with small molecules on cell Ca2+ signaling
方琰, Y Fang, M Rang, L He
Blamed & Pharmacothee 1998: 52: 459-64,-0001,():
-1年11月30日
Summary-Interactions of the Na+-Ca2+ exchanger with small molecules on celt Ca2+ signaling were elucidated in Chinese hamster ovary (CHO) CI cells, which transfected a control vector without any expression of the Na*-Ca2+ exchanger's gene while CHO CK 1.4 cells transfected an expression vector encoding the bovine cardiac Na+-Caz+ exchanger's eDNA, treated with lithium or sodlum-buffer medRIm respectively, by using L16(2)15 muhifaetnrial orthogonal stallstics and fura-2 fluorescence real-time intaging In contrast to controls of Li*-treated Cl cells, [he store dependent CaZ+-influx (SDCI) was enhanced by either the Na*-Ca2+ exchanger, Na+, 1-β-3-(4-methoxyphenvl)propnxy1-4-methoxyphcnethyl}-IH-im daze e HC (SK&F96365 of nuahain. and by interactions of the Na*-Ca2+ exchanger with either Na" SK&F96365 or both SK&F96365 and ouabain; and ATP induced Ca2+. release (AICR) was activated by SK&F96365 or Na+ alone, interactions of the Na+-Ca2+ exchanger with SK&F96365 or Na+, and an interaetion between SK&F96365 and ouabain The dramatic interaction of the Na+-Ca2+ exchanger with small molecules indieates that cell Ca2+ signaling is generated by nositol triphnsphale (InsP3)-dependent pathways, allnsterie effects el the G protein coupled P2y&2u. purinoceptor and mnlti-sile recognition Our findings provide meaningful clues for designing new strategies of cardiocerebral vascular oxidative diseases
CHO cells/, calcium metabolism/, cations/, membrane proteins/, multifactorial interactions
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方琰, Y. Fang*, M. Hu, K. Liu
Biomed Pharmacother 2001; 55: 102-10,-0001,():
-1年11月30日
Summary-Ras-VEGF concerned angiogenesis is correlated with oncogene maintenance, tumori-gagesis, metastasis and resistance to anti cancer therapies; however, this association is not clearly elucidated by serum VEGF, due to VEGF signalling in blood cells themselves The present study aimed to elucidate tumorigenic VEGF eignalling in eight human HCC cell types and reveal the kinetics of tumorigenic VEG F signalling in three time intervals, thereby discovering the relationships Of VEGF concemed argiogenesis signalling with the extent of the human HCC cell growth, metastasis and resistance to anti-cancer drugs, by using the poorly metastatic SMMC7721, 7402/D+ (doxorubicin- resistance) and 7402/b (dOxoruhicin withdrawal), the highly metastatic MHCC1 non-transfected human HCC cell lines, and the highly melaetatic A3-1, FS, Ftf and E3 human HCC cell lines trans teated with exgressing green fluorescence protein into the phenotype of MHCC1 ceils, and quantita- tive 'sandwtch" ELISA analyses. The unique results indicated attdbetes and objective taws as follows Human HCC cell growth requites time dependent tumorigenic VEGF signalling; levets ot VEGF sig nailing are positively correlated with each cell phenotyge itself; and levels at VEGF signalling are inversely correlated with the possibility of rnetaslaSis and drug resistance. The contrast data first feveal important elues for exploring dual metastatic mechanisms via tumor celt-generated non- endothelium vasculogenesis and VEGF-endetheliurn-attached anglogeneeis that may be essential for developing novel strategies aimed at VEGF-concerned signal networks in iSchemic/metastatic dis- eases arid transgenic models.
angiogenesis/, cytokines/, tumor biology
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方琰, Y. Fang*, M. Hu, K. Liu
Biomed Pharmacother 2002; 56: 50-5,-0001,():
-1年11月30日
The 'angiogenic switch' concept has been used to discover various pro-and anti-angiogenic molecules as pharmacotherapeutic strategies for cancers and other ischemic and inflam matory diseases; however, surprisingly little is known about the tumor angiogenic switch' in response to complex interplay between environmental and genetic mechanisms that are most impodantiy, hypothesis-ddven, largely unsolved at the postgenomic level The present study's aim is to identify those interplays between the expressing green fluorescence protein (EGFP) transcript and redoxdriven vascular endothelial growth factor (VEGF) upstream mechanisms that influence tumodgenic VEGF signalling, by using mugifactorial orthogonal statistical analyses, the non-transfected and trans-fected human hepatoceliular carcinoma (HCC) cell lines, and quantitative 'sandwich' Elisa immunoas-says. Tbe unique results indicate valuable findings on the postgenomic level as follows. Fusion of the EG FP significantly triggers tumorigenic VEG F signalling in th roe E3-, F11-and A31-transfected human HCC cell lines, compared with the parental EGFP-free malignant hepatocellular carcinoma (MHCC)I celIline; Redox-regulated VEGF upstream mechanism interplays dramatically mediate dual responses, either down or upregulating tumorigenic VEGF signalling, which depends on individual post-transcriptional regulation or upstream modification of the VEGF promoter in the three MHCC1, SMCCC7721 and doxerubicin-resistance 7402/D+ non-transfected human HCC cell lines; and mechanism-based strategies for stimulating β-adrenergic and P2-purinergic signal transduction and counteracting O2-and Ca2+-inflow significantly trigger tumodgenic VEGF signalling in ATRA/ATRP-driven networks, compared with controls of the non-transfected cell types examined. The contrast data offer first pilot paradigms of searching for hypothesis-driven multgactorial interplays on tumori-genic VEGF signalling, which are valuable for further deciphedng postgenome-wide VEGF upstream regulatory networks of switching on the tumor angiogenesis, and developing mechanism-based novel pharmacotherapeutic strategies.
angiogenic signalling/, postgenomic mechanisms/, tumor biology
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