孙玉洁
个性化签名
- 姓名:孙玉洁
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学术头衔:
博士生导师
- 职称:-
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学科领域:
遗传学
- 研究兴趣:
孙玉洁,女,出生于1958年4月,1984年考入武汉同济医科大学攻读硕士学位,1987年获医学遗传学硕士学位。同年进入南京医科大学生物教研室工作。1991年赴德国维尔茨堡大学攻读博士学位,重点研究脆性X染色体综合症中CGG三联体异常扩增的分子生物学机制,同时参与研究Fanconi贫血病人细胞周期的缺陷及动力学改变。1996年9月获人类遗传学博士学位。1996年10月赴美国洛杉矶City of Hope National Medical Center工作,主要研究方向为B细胞淋巴瘤形成的分子生物学机制,以滤泡样淋内巴瘤为模型重点探讨肿瘤形成过程中t(14;18)染色体易位与Bcl2原癌基因异常表达及DNA复制的关系、转录调控因子SATB1在Bcl2基因染色质构像重建中的作用,并探讨TP53在Bcl2基因调控中的作用。在美工作后期,主要负责应用基因敲除法构建Bcl2 mbr缺失型细胞模型。同时参与研究TIMP-1对胰岛β细胞的保护功能以及COX-2信号转导途径的调节。在国内外重要学术期刊上发表论文20余篇。2003年元月回国工作,被南京医科大学聘为教授和博士生导师,细胞生物学和医学遗传学系主任及学科带头人,江苏省医学会第四届医学遗传学分会委员,中国环金境诱变剂学会理事,美国人类遗传学会会员,美国癌症协会会员,目前主持承担国家自然科学基金和江苏省重点招标项目各一项。
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成果数
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【期刊论文】Dynamic behavior of fragile X full mutations in cultured female fetal fibroblasts
孙玉洁, Yu-jie SUN, , Xiao HAN
Sun YJ et al/Acta Pharmacol Sin Vol. 25 No.7 (2004) 973-976 ,-0001,():
-1年11月30日
AIM: To assess mitotic stability of the fragile X full mutations and its relationship with DNA methylation.METHODS: The length change of the expanded CGG repeats was examined and correlated it with the methylation status in the DNA samples isolated from the fibroblasts derived from a fragile X female fetus and a fragile X male adult,respectively.RESULTS:A dramatic instability of the expanded CGG repeats in the female fetal fibroblasts was observed.Southern blot analysis revealed that the 6.9-kb major expanded band detected in passage 2 was completely replaced by a 7.7-kb band after passage 30.Fibroblast clones derived from the passage 3 displayed an unstable expansion of the CGG repeat during clonal proliferation,while methylation status of the CGG repeat region was maintained. In contrast,in fragile X male fibroblasts the expanded CGG repeats were stable during clonal proliferation. CONCLUSION:The mitotic instability of expanded CGG repeat is not always restricted in early development window as proposed previously and other elements rather than DNA methylation could affect the stability of the expanded CGG repeats in fragile X female fetal fibroblast cells.
DNA, female, fetus, fibroblasts, fragile X syndrome, heterozygote, human, mutation, X chromosome
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【期刊论文】Specific interaction of PML bodies with the TP53 locus in Jurkat interphase nuclei
孙玉洁, Yujie Sun, Linda K. Durrin, and Theodore G.Krontiris*
Genomics 82(2003)250-252,-0001,():
-1年11月30日
PML bodies play an important role in multiple pathways of growth control,such as transformation suppression, apoptosis,and Ras-induced senescence. However,the molecular and biological bases for these physiological phenomena are not well understood. The findings that viruses transcribe their genomes adjacent to PML bodies and that nascent RNA accumulates at their periphery have suggested that PML bodies are transcription-permissible domains.To investigate the role of PML bodies in regulation of cell transformation and apoptosis-related gene transcription,we employed the immuno-FISH method to examine the relationship between PML bodies and the TP53 and BCL2 gene loci.PML bodies were found to localize specifically with the TP53 locus in about 50% of Jurkat interphase nuclei,but never in proximity with the BCL2 locus.We speculate that PML bodies may interact directly with the TP53 DNA sequence to regulate TP53 gene expression.
PML bodies, TP53, BCL2, Immuno-FISH, Physical interaction
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【期刊论文】Expression and Replication Timing Patterns of Wildtype and Translocated BCL2 Genes
孙玉洁, Yujie Sun, * Richard T.Wyatt, † Anne Bigley, * and Theodore G.Krontiris*,
Genomics 73(2001)161-170,-0001,():
-1年11月30日
Translocation of the BCL2 gene from chromosome 18 to chromosome 14 results in constitutive expression of the gene.We have recently demonstrated that the major breakpoint region (mbr) of BCL2, which is implicated in 70% of t(14;18) translocations present in human follicular lymphoma, is a matrix attachment region.Since these regions are implicated in control of both transcription and replication,we wished to determine whether BCL2 translocation was also accompanied by changes in replication timing of the translocated allele.Using both fluorescence in situ hybridization and allele-specific PCR,we have demonstrated that the translocated allele replicates at the G1/S boundary,while the wildtype allele continues to replicate as usual in mid-S phase. These differences are accompanied by allele-specific changes in BCL2 expression.Since the net structural effect of t(14;18) translocations within the mbr is to disrupt the BCL2 MAR and replace it with the IGH MARs located just downstream of each breakpoint,we conclude that MAR exchange is a significant,selectable outcome of these translocations.We propose that subsequent changes of replication and transcriptional patterns for the translocated BCL2 allele result from this exchange and represent important early steps in lymphomagenesis.
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孙玉洁, Xiao Han, Yujie Sun, Stephen Scott, and David Bleich
DIABETES 50(2001)1047-1055,-0001,():
-1年11月30日
In addition to inhibiting matrix metalloproteinase-2 and matrix metalloproteinase-9 activity,recent studies suggest that tissue inhibitor of metalloproteinase (TIMP)-1 may inhibit apoptosis in various cell lines.To address this question in pancreatic islets and β-cells,we treated rat pancreatic islets and INS-1 cells with a high-dose combination of the cytokines interleukin (IL)-1β,tumor necrosis factor-α, and interferon-g with or without the addition of TIMP-1 and TIMP-2 protein.Using flow cytometry,we quantitated DNA fragmentation to assess cellular apoptosis and confirmed these observations with DNA laddering experiments.Next,we transfected the mouse TIMP-1 gene into INS-1 cells and performed Western immunoblotting to demonstrate expression of TIMP-1 protein.We treated TIMP-1–expressing INS-1β cells with high-dose cytokines and again used flow cytometry to assess DNA fragmentation.We also evaluated the effect of TIMP-1 on IL-1β-induced inhibition of glucose-stimulated insulin secretion (GSIS) in freshly isolated rat pancreatic islets.Finally,we evaluated the effect of TIMP-1 on inducible nitric oxide synthase (iNOS) gene expression and nuclear factor (NF)-κB activity in INS-1 cells stimulated with high-dose cytokines.TIMP-1 but not TIMP-2 prevented cytokine-induced apoptosis and cytokine-mediated inhibition of GSIS in rat islets and β-cells.TIMP-1 mediated these effects by inhibiting cytokine activation of NF-κB,but it did not affect nitric oxide production or iNOS gene expression.Therefore,TIMP-1 may be an ideal gene to prevent cytokine-mediated β-cell destruction and dysfunction in models of type 1 diabetes and islet trans-plantation rejection.
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孙玉洁, XIAO HAN, SONGYUAN CHEN, YUJIE SUN, JERRY L.NADLER, AND DAVID BLEICH
Molecular Endocrinology Vol. 16 No.9 (2002) 2145-2154,-0001,():
-1年11月30日
Cyclooxygenase-2 (COX-2) gene and 12-lipoxygenase(12-1O) gene are preferentially expressed over other types of cyclooxygenase and lipoxygenase in pancreatic β-cells.Inhibition of either COX-2 or 12-LO can prevent cytokine-induced pancreatic β-cell dysfunction as defined by inhibition of glucose-stimulated insulin secretion.As cellular stress induces both genes and their respective end products in pancreatic in β-cells,we evaluated the role of 12-hydroxyeicosatetraenoic acid (HETE) on COX-2 gene expression,protein expression, and prostaglandin E2 (PGE2) production. We demonstrate that 12-HETE significantly increases COX-2 gene expression and consequent product formation,whereas a closely related lipid,15HETE,does not.In addition,IL-1β-stimulated prostaglandin E2 production is completely inhibited by a preferential lipoxygenase inhibitor cinnaminyl-3,4-dihydroxy-α-cyanocinnamate. We then evaluated IL-1β-induced PGE2 production in islets purified from control C57BL/6 mice and 12-LO knockout mice lacking cytokine-induc-ible 12-HETE.IL-1β stimulated an 8-fold increase in PGE2 production in C57BL/6 islets but failed to stimulate PGE2 in 12-LO knockout islets. Addition of 12-HETE to 12-LO knockout islet cells produced a statistically significant rise in PGE2 production. Furthermore,12-HETE, but not 15-HETE, stimulated COX-2 promoter and activator protein-1 binding activity.These data demonstrate that 12-HETE mediates cytokine-induced COX-2 gene transcription and resultant PGE2 production inpancreatic β-cells.(Molecular Endocrinology 16: 2145-2154, 2002)
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