马骊
1.T细胞识别活化的基础和应用研究。2.干细胞基因治疗研究。
个性化签名
- 姓名:马骊
- 目前身份:
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学术头衔:
博士生导师, 教育部“新世纪优秀人才支持计划”入选者
- 职称:-
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学科领域:
人体免疫学
- 研究兴趣:1.T细胞识别活化的基础和应用研究。2.干细胞基因治疗研究。
马骊,生物技术系(分子免疫学研究所)主任,博士,教授,博士生导师。
近五年来,主持国家“十一五”863计划、“十五”863计划、政府间国际科技合作、国家自然科学基金等省部级以上科研课题18项,获资助692.5万元;作为副组长,协助主持国家重大科技攻关计划、“十五”863计划等省部级以上科研课题5项。获广东省科技进步一等奖1项(第一完成人)、二等奖1项、三等奖2项,申请国家发明专利4项,获专利证书2项,获国家II类新药证书1项。在国内外杂志上发表论文97篇、SCI收录24篇,参编专著2部。2006年荣获第八届广东省丁颖科技奖,并被评为广东省高等学校“千百十工程”第四批省级培养对象,2007年入选教育部新世纪优秀人才支持计划,2008年被评为第二届“南医优秀教师”,2009年入选南方医科大学首届“国家杰出青年科学基金培育计划”。
研究方向:1.T细胞识别活化的基础和应用研究:① 外周αβ T淋巴细胞TCR二次重排方向性研究;② T细胞免疫相关疾病TCR CDR3谱型研究;③ 抗原特异TCR在抗结核免疫治疗中的应用。2.干细胞基因治疗研究:① HGF基因修饰骨髓基质干细胞治疗股骨头缺血性坏死的研究;② HGF基因修饰骨髓基质干细胞治疗缺血性心脏病的研究。
个人主页:http://web2.fimmu.com/swjs/xyjg.asp?classid=5
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成果数
9
【期刊论文】Expression,Purification,and Refolding of Recombinant Fusion Protein hlL-2/mGM-CSF.
马骊, QIAN WEN#, LI MA#, WEI LUO#, MING—QIAN ZHOU#, AND XIAO NING WANG#
BIOMEDICALAND ENVIRONMENTAL SCIENCES 21, 509-513 (2008),-0001,():
-1年11月30日
To study the activities of interleukin(IL)-2 and granulocyte-macrophage colony-stimulating factor(GM-CSF)(hlL-2linGM-CSF). Methods SOE PCR was used to change the linker of the fusion protein for higher activities. The fusion protein was expressed in Escherichia colf (Ecoli) BL21 (DE3) in inclusion body (IB) form. Afler IB was extracted and clarified. it was denatured and purified by afinity chromato graphy. The protein was refolded by dilution in a L-arginine refolding buffer and refined by anion chromatography. The protein activity was detected by cytokine-dependent cell proliferation assay. Results The expression of hlL-2/mGM-CSF in E coli yielded approximately 20 mg protein/L culture and the purity was about 90%.The specific activities of 1L-2 and GM-CSF were 54xl0. IU/mg and 7.1xl0. IU/mg. respectively. Conclusion This research provides important information about the anti. tumor activity of hiL-2/mGM-CSF r/vivo. thus facilitating future clinical research on hlL-2/mGM-CSF used in immune therapy.
HIL-2/, mGM-CSF, Fusion protein, Purification, Refolding
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【期刊论文】A Rabbit Model of Hormone-induced Early Avascular Necrosis of the Femoral Head.
马骊, QIAN WEN#, Ll MA#, YAN—PING CHEN&, LIN YANG&, WEI LUO#, AND XIAO-NING WANG*
BIOMEDICAL AND ENVIRONMENT L SCIENCES 21, 398-403 (2008),-0001,():
-1年11月30日
0biective To establish an experimental model of early stage avascular necrosis of the femoral head(ANFH)caused by corticosteroid in adult rabbits and to observe the pathological changes with various imaging techniques. Methotis ANFH was induced by fl combination of hypersensifivity vasculitis caused by injection of horse serum and subsequent administration of a high dose of corticosteroid.The pathological changes were detected with digital radiography(DR), computed tomography(CT), magnetic resonance imaging(MRI), ink artery infusion angiography, hematoxylin-eosin staining, and immunohistochemistry.Results The imageological and pathological changes corresponded to the clinical characteristics of early stage ANFH.DR showed bilaterally increased bone density.an unclear epiphyseai line, and blurred texture of cancellous bone.CT showed spot-like low-density imaging of cancellous bone thinner cortical bone, osteoporosis, and an unclear epiphyseal Iine.MRI showed bone marrow edem a and spot-like high signals in T2-weighted imaging in cancellous bone.Ink artery infusion angiography showed fewer obstructed blood vessels in the femoral head.I1E staining of pathological sections showed fewer trabeculae and thin bone, an increased proportion of empty osteocyte lacunae, decreased hematopoiesis, thrombosis, and fat eell hypertrophy. tmmunohistochem istry showed attenuated expression of vascular endothelial growth factor in osteoblasts and chondrocytes, and on the inner membrane of blood vessels. Conclusion Experimental rabbit mode1 of early stage ANFH caused by corticosteroid can be successfully established and provide the foundation for developing effective me山ods to treat early stage ANFH
Avascular necrosis of the femoral head: Corticosteroid: Animal model
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马骊, Tao Liu†, Qian Zhang†, , Lingling Wang†, Lu Yu, Wenchuan Leng, Jian Yang, Lihong Chen, Junping Peng, Li Ma, Jie Dong, Xingye Xu, Ying Xue, Yafang Zhu, Wenliang Zhang, Li Yang, Weijun Li, Lilian Sun, Zhe Wan, Guohui Ding, Fudong Yu, Kang Tu, Ziliang Qian, Ruoyu Li, Yan Shen, Yixue Li and Qi Jin*
BMC Genomics 2007, 8: 100,-0001,():
-1年11月30日
We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD). A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions.
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【期刊论文】Research article Analysis of the dermatophyte Trichophyton rubrum expressed sequence tags
马骊, Lingling Wang†, Li Ma†, Wenchuan Leng†, Tao Liu, Lu Yu, Jian Yang, Li Yang, Wenliang Zhang, Qian Zhang, Jie Dong, Ying Xue, Yafang Zhu, Xingye Xu, Zhe Wan, Guohui Ding, Fudong Yu, Kang Tu, Yixue Li, Ruoyu Li, Yan Shen and Qi Jin*,
BMC Genomics 2006, 7: 255,-0001,():
-1年11月30日
Dermatophytes are the primary causative agent of dermatophytoses, a disease that affects billions of individuals worldwide. Trichophyton rubrum is the most common of the superficial fungi. Although T. rubrum is a recognized pathogen for humans, little is known about how its transcriptional pattern is related to development of the fungus and establishment of disease. It is therefore necessary to identify genes whose expression is relevant to growth, metabolism and virulence of T. rubrum.
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马骊, Guang-Ping Ruan a, Li Ma a, *, Min-Jie Meng a, Yong Zhu c, Ze-Hong Chen c, Ying Lin b, Zheng-Qiang Wu b, Xiao-Wei He b, Ju-Fang Wang b, Xiao-Ning Wang b
Journal of Immunological Methods 312(2006)148-156,-0001,():
-1年11月30日
Different methods were used to prepare HLA tetramers and the yields of each method were compared. Our results indicate that preliminary refolding of the heavy chain (Hc) and light chain (β2m) yields more monomer than the typical conventional method with urea-solubilized Hc and β2m. We then used the corresponding tetramers to detect cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL). Increasing data suggest that the adoptive transfer of CMV-specific CTL constitutes an effective strategy against CMV infections. We designed a method that efficiently induces CMV-specific CTL to a higher frequency in vitro than is currently achieved. This method increased the percentage of CMV-specific CTL from below 1% to 20% of PBL, accounting for more than 40% of CD8+ T cells. Successful HLA tetramer preparation provides the basis for the subsequent detection of CMVspecific CTL in clinical applications.
Class I HLA tetramers, CMV-specific CTL, Preparation, Detection
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马骊, Guang-Ping Ruan a, Li Ma a, Xiao-Wei He b, Min-Jie Meng a, Yong Zhu c, Ming-Qian Zhou a, Zhi-Ming Hu a, Xiao-Ning Wang a, b, *
Protein Expression and PuriWcation 44(2005)45-51,-0001,():
-1年11月30日
The importance of eggs as a source of speciWc antibodies is well recognized. Egg yolk contains 8-20 mg immunoglobulins (IgY) per milliliter. However, the major problem in separating IgY is to remove the high concentrations of lipids in egg yolk. We Wrst used water dilution method to get the supernatant containing IgY, then puriWed the antibody by caprylic acid–ammonium sulfate method, and obtained speciWc antibody with satisfactory purity and activity. By comparison of these several methods, each has its advantages, one can be chosen to purify IgY according to practical need. The puriWed IgY produced by the immunized chickens can stain the human peripheral blood mononuclear cell eVectively when labeled with Xuorescent FITC.
Egg yolk, IgY, Immunoglobulin extraction, Caprylic acid, HLA-A*, 0201 heavy chain, β2-Microglobulin, IgY-FITC
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马骊, Qi-Rui Wanga, Li Maa, Ming-Qian Zhoua, Nu-Yun Liua, Shen-Rong Jingb, Quan-Ming Zoub, Xiao-Ning wanga, *
Protein Expression and PuriWcation 39(2005)131-136,-0001,():
-1年11月30日
Interleukin-2 (IL-2) can stimulate T cell proliferation and diVerentiation when binding to its receptor on T cells. It produces a marked eVect by enhancing the cytotoxicity of CD8+ T cells and natural killer cells. Granulocyte-macrophage colony stimulating factor (GM-CSF) is associated with many cells proliferation, such as dendritic cells, macrophages. Here, we report the construction, expression and puriWcation of a bifunctional protein, hIL-2/GM-CSF, which may facilitate interaction between T cells and the antigen presentation cells and improve the eYciency of antigen presentation. We found that the use of chemicals and temperature shift is a peculiar system for induction of the Escherichia coli transformed with an IPTG-regulated hIL-2/GM-CSF expression vector in this research. After renaturation, anion exchange chromatography, metal aYnity chromatography, and strict endotoxin-free cation exchange chromatography, the fusion protein devoid of endotoxin showed high purity. Cell proliferation experiments proved that this bifunctional protein retains both hIL-2 and GM-CSF biological activities. These results will facilitate the numerous subsequent studies on this bifunctional molecule.
Interleukin-2, Granulocyte-macrophage colony stimulating factor, Bifunctional molecule, Expression, Renaturation, PuriWcation, Bioactivity
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【期刊论文】Analysis of part of the Trichophyton rubrum ESTs
马骊, WANG Lingling*, MA Li, *, †, LENG Wenchuan, YANG Jian, ZHU Junping, DONG Jie, XUE Ying, WAN Zhe, LI Ruoyu & JIN Qi
Science in China Ser. C Life Sciences 2004 Vol. 47 No.5 389-395,-0001,():
-1年11月30日
Trichophyton rubrum (T. rubrum) is the most common of the superficial fungi. In an effort to better understand the genetic and biochemical makeup of T. rubrum, we generated cDNA libraries from 3 growth stages and used these to isolate 4002 unique expressed sequence tags (ESTs). Sequence comparisons with the Genbank database allowed 1226 of the ESTs to be assigned putative functions or matched with homologs from other organisms. Of the remaining ESTs, 989 were only weakly similar to known sequences and 1787 had no identifiable functions, suggesting that they represent novel genes. We further analyzed the presence of several important genes involved in the growth, metabolism, signal transduction, pathogenesis and drug resistance in T. rubrum. This information was used to newly elucidate important metabolic pathways in T. rubrum. Taken together, our results should form the molecular basis for continued research on the physiological processes and pathogenic mechanisms of T. rubrum, and may lead to a better understanding of fungal drug resistance and identification of new drug targets.
Trichophyton rubrum,, functional genomics,, cDNA library,, expressed sequence Tags,, drug targets.,
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马骊, MA Li (马骊), ZHANG Zhiqing (张智清), WANG Xiaoning (王小宁), SUN Dajun (孙大军), ZHOU Xiaoming (周小明), CHEN Aijun (陈爱君) & YAO Lihong (姚立红)
SCIENCE IN CHINA (Series C) October 2001 Vol. 44 No.5,-0001,():
-1年11月30日
Four human vascular endothelial growth factor receptor Flt-1 cDNA fragments containing extracellular domain loops 2, 1-2, 2-3 and 1-3 respectively were amplified from human placental cDNA library by PCR and used for screening ligand binding domains by yeast two-hybrid system. The result showed that, not only loop 1-3, but also the smaller fragment loop 2-3 could bind to hVEGF165. Recombinant expression plasmids pPIC9K/Flt-1(1-3) and pPIC9K/Flt-1(2-3) were constructed and transformed to Pichia. pastoris host strain GS115, cultured in flasks, and expressed under the induction of 1% methanol. The expressed product existed in supernatant in the form of soluble molecules and contained more than 60% of total protein after being induced for 4d. After being purified by CM-Sepharose FF and Sephacryl S-100 chromatography, its purity reached above 90%. Biological assay in vitro showed that the binding capacity of expressed soluble Flt-1(2-3) to hVEGF165 and its inhibiting effect on the proliferation of human umbilical veins endothelial cells (HUVEC) stimulated with hVEGF165 were close to those of sFlt-1(1-3). Animal test showed that sFlt-1(2-3) could inhibit the formation of regenerate blood vessels stimulated with hVEGF165 significantly.
vascular endothelial growth factor (, VEGF), ,, receptor,, yeast two-hybrid,, Pichia., pastoris,, gene expression.,
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