肖洲生
分子药理学
个性化签名
- 姓名:肖洲生
- 目前身份:
- 担任导师情况:
- 学位:
-
学术头衔:
博士生导师
- 职称:-
-
学科领域:
药物化学
- 研究兴趣:分子药理学
肖洲生,男,1964年出生,教授,博士生导师。1987年毕业于衡阳医学院医疗系本科并获临床医学学士学位,毕业后在湖南医科大学药理学任讲师,此后一直致力于分子药理学的教学与科研。1987-1993年,先后从师于我国著名心血管药理学家陈修教授,李元建教授等进行药物防治心肌缺血/再灌注损伤的研究,该课题1998年获国家教育部科技进步三等奖。1993-1995年,从师于我国著名遗传药理学家周宏灏教授,进行药物代谢酶个体和种族差异及其分子机理的研究。1995-1996年,在美国国立环境与健康研究所进行博士后研究,从师于美国著名药理学家Goldstein JA教授, 进行CYP2C19酶在中国人群中的基因突变分析。该课题1999-2003年先后获教育部科学技术进步一等奖和中华医学奖一等奖。1996-1999年,在美国杜克大学医学中心任副研究员,从师于美国著名骨与矿物质代谢疾病研究专家Quarles LD教授, 进行成骨细胞分化的基因调控研究。1999-2001年,中南大学湘雅医学院分子药理研究室任副主任,副教授,硕士研究生导师,从事用药物与基因干预骨髓间质干细胞向成骨细胞分化的调控研究。2002年至今,中南大学临床药理研究所分子药理研究室主任,教授,博士研究生导师。2001年至今,先后在美国杜克大学医学中心骨与矿物质研究所、美国Kansas州立大学医学中心肾脏研究所任助理教授,从事转基因小鼠模型探讨骨髓间质干细胞向成骨细胞分化的调控机制,力求在理论和实践上为防治骨代谢性疾病拓开新的途径。该研究得到美国NIH基金和中国国家自然科学基金资助,研究论文曾先后多次被ASBMR国际会议采用,作大会发言和精选墙报展示,受到与会专家一致好评。曾在《J Biol Chem》、《J Pharmacol Exper Ther》、《Gene》、《Am J Physiol》、《J Cell Biochem》等国际核期刊发表第一作者论文数十篇,多篇论文被国内外学者引用,有较高的学术价值和影响力。目前正致力于Cbfa1基因表达调控的研究,开发防治骨质疏松症的新药,为在基因和细胞水平治疗骨质疏松症提供新的途径。
-
主页访问
1988
-
关注数
0
-
成果阅读
395
-
成果数
9
肖洲生
,-0001,():
-1年11月30日
-
49浏览
-
0点赞
-
0收藏
-
0分享
-
71下载
-
0评论
-
引用
【期刊论文】Intrinsic mineralization defect in Hyp mouse osteoblasts
肖洲生, Z. S. XIAO, M. CRENSHAW, R. GUO, T. NESBITT, M. K. DREZNER, AND L. D. QUARLES
,-0001,():
-1年11月30日
Intrinsic mineralization defect in Hyp mouse osteoblasts. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E700-E708, 1998.-X-linked hypophosphatemia (XLH) is caused by inactivating mutations of PEX, an endopeptidase of uncertain function. This defect is shared by Hyp mice, the murine homologue of the human disease, in which a 38 Pex deletion has been documented. In the present study, we report that immortalized osteoblasts derived from the simian virus 40 (SV40) transgenic Hyp mouse (TMOb-Hyp) have an impaired capacity to mineralize extracellular matrix in vitro. Compared with immortalized osteoblasts from the SV40 transgenic normal mouse (TMOb-Nl), osteoblast cultures from the SV40 Hyp mouse exhibit diminished 45Ca accumulation into extracellular matrix (37±6 vs. 1,484±68 counts·min-1 ·μg protein-1) and reduced formation of mineralization nodules. Moreover, in coculture experiments, we found evidence that osteoblasts from the SV40 Hyp mouse produce a diffusible factor that blocks mineralization of extracellular matrix in normal osteoblasts. Our findings indicate that abnormal PEX in osteoblasts is associated with the accumulation of a factor(s) that inhibits ineralization of extracellular matrix in vitro.
X-linked phosphaturia, osteomalacia, osteocalcin
-
26浏览
-
0点赞
-
0收藏
-
0分享
-
100下载
-
0评论
-
引用
【期刊论文】Inhibition of MEPE cleavage by Phex
肖洲生, Rong Guo, a Peter S.N. Rowe, b Shiguang Liu, a Leigh G. Simpson, a Zhou-Sheng Xiao, a and L. Darryl Quarlesa, *
Biochemical and Biophysical Research Communications 297(2002)38-45,-0001,():
-1年11月30日
X-linked hypophosphatemia (XLH) and the Hyp-mouse disease homolog are caused by inactivating mutations of Phex which results in the local accumulation of an unknown autocrine/paracrine factor in bone that inhibits mineralization of extracellular matrix. In these studies, we evaluated whether the matrix phosphoglycoprotein MEPE, which is increased in calvaria from Hyp mice, is a substrate for Phex. Using recombinant full-length Phex (rPhexWT) produced in Sf9 cells, we failed to observe Phexdependent hydrolysis of recombinant human MEPE (rMEPE). Rather, we found that rPhex-WT inhibited cleavage of rMEPE by endogenous cathepsin-like enzyme activity present in Sf9 membrane. Sf9 membranes as well as purified cathepsin B cleaved MEPE into two major fragments of 50 and 42 kDa. rPhexWT protein in Sf9 membrane fractions, co-incubation of rPhexWT and cathepsin B, and pre-treatment of Sf9 membranes with leupeptin prevented the hydrolysis of MEPE in vitro. The C-terminal domain of Phex was required for inhibition of MEPE cleavage, since the C-terminal deletion mutant rPhex (1-433) [rPhex30M] failed to inhibit Sf9-dependent metabolism of MEPE. Phex-dependent inhibition of MEPE degradation, however, did not require Phex enzymatic activity, since EDTA, an inhibitor of rPhex, failed to block rPhexWT inhibition of MEPE cleavage by Sf9 membranes. Since we were unable to identify interactions of Phex with MEPE or actions of Phex to metabolize cathepsin B, Phex may be acting to interfere with the actions of other enzymes that degrade extracellular matrix proteins. Although the molecular mechanism and biological relevance of non-enzymatic actions of Phex need to be established, these findings indicate that MEPE may be involved in the pathogenesis defective mineralization due to Phex deficiency in XLH and the Hyp-mouse.
M13 endopeptidase, Mineralization, Bone, XLH, Hyp
-
34浏览
-
0点赞
-
0收藏
-
0分享
-
142下载
-
0评论
-
引用
肖洲生, Z.S. Xiao, R. Thomas, T.K. Hinson, L.D. Quarles *
Gene 214(1998)187-197,-0001,():
-1年11月30日
Although the CBFA1 gene encodes an osteoblast-specific transcription factor that regulates osteoblast differentiation, uncertainty exists about the organization of its 5¾ end and the relevance of a novel N-terminal sequence identified in the mouse Cbfa1/Osf2 isoform. We found the novel 5'Cbfa1/Osf2 sequence is encoded by a previously unrecognized upstream exon, designated exon−1, which is highly conserved in mouse, rat and human. In addition, two splice donor sites may be utilized to generate Cbfa1/Osf2 cDNAs containing different N-terminal sequences. The first ATG and splice donor site in exon −1 is predicted to transcribe a cDNA containing the unique Osf2 5¾ sequence, whereas a second donor splice site gives rise to cDNAs that contain sequences encoding an 11 amino acid insert. In the human CBFA1 gene, an additional 2-bp nucleotide insert shifts the reading frame and results in stop codons in the cDNA sequence derived from exon−1. The 5'-most exon of the human CBFA1 gene, therefore, contains the 5'non-coding region rather than a human OSF2 homolog. The absence of a homologous OSF2 coding sequence in the human CBFA1 cDNA suggests that the novel mouse N-terminal Osf2 sequence is not essential for functioning of the CBFA1 gene product. In addition, multiple transcripts derived from a single CBFA1/Cbfa1 gene were detected in osteoblasts by Northern analysis and RT-PCR, including additional Cbfa1/Osf2 isoforms containing deletions of exons 1 and 4. Thus, the alternative use of transcription start sites and splicing leads to the genesis of CBFA1/Cbfa1 isoforms with possible differences in transactivation potentials.
Core-binding factor, PEBP2aA, AML-3, Osteoblast, Differentiation
-
64浏览
-
0点赞
-
0收藏
-
0分享
-
108下载
-
0评论
-
引用
【期刊论文】CYP2C19 genotype and S -mephenytoin 4
肖洲生, Nan He
EurJ Clin Pharmacol (2002) 58: 15-18,-0001,():
-1年11月30日
Aims: To investigate the incidence of the CYP2C19 polymorphism in the Chinese Dai population. Methods: One hundred and ninety-three healthy Chinese Dai volunteers were identified with respect to CYP2C19 by genotype and phenotype analyses. A polymerase chain reaction-restriction fragment length polymorphism method was performed for genotyping procedures. The 4¢-hydroxymephenytoin (4¢-OH-MP) and S/R-mephenytoin (S/R-MP) excreted in the urine were determined by high-performance liquid chromatography and gas chromatography, respectively. Results: Eighteen subjects were identified as poor metabolisers (PMs). The frequency of PMs in the Chinese Dai subjects was 9.3% (95% confidence interval 5.2, 13.4), which is lowerthan that in the Chinese Han population (P<0.05). Chinese Dai subjects had a higher frequency of the mutant CYP2C19*2 allele (0.303) and a lowerfr equency of the mutant CYP2C19*3 allele (0.034). These two mutant alleles could explain all deficiencies of CYP2C19 activity in the Chinese Dai subjects. The frequency of the CYP2C19*3 allele is significantly lowerthan that in the Chinese Han population (P<0.05). The mean S/R ratio was lower in the homozygous extensive metabolisers (EMs) compared with that in heterozygous EMs (P<0.01), and the latter was lowerthan that in the PMs (P<0.01). Furthermore, the mean S/R ratio in CYP2C19*3/CYP2C19*2 heterozygous PMs was possibly lower than that in the CYP2C19*2/CYP2C19*2 homozygous PMs (P<0.05). Conclusion: The frequencies of PMs and CYP2C19*3 allele in the Chinese Dai population are significantly lowerthan those in the Han population. The CYP2C19 genotype analysis is largely consistent with the mephenytoin phenotype analysis. The variability of S/R ratios in EMs and PMs shows a gene–dosage effect.
S-mephenytoin
-
36浏览
-
0点赞
-
0收藏
-
0分享
-
71下载
-
0评论
-
引用
【期刊论文】Characterization of the Upstream Mouse Cbfa1/Runx2 Promoter
肖洲生, Z. S. Xiao, Shi-Guang Liu, T. K. Hinson, and L. D. Quarles*
Journal of Cellular Biochemistry 82: 647-659 (2001),-0001,():
-1年11月30日
Cbfa1 (or Runx2/AML-3/PEPB2a) is a transcriptional activator of osteoblastic differentiation. To investigate the regulation of Cbfa1 expression, we isolated and characterized a portion of the 50-
trans, c, r, i, p, t, ion factors, Cbfa1, Osf2, osteoblasts, Runx2
-
19浏览
-
0点赞
-
0收藏
-
0分享
-
187下载
-
0评论
-
引用
肖洲生, Yuan-Jian Li*, Zhou-Sheng Xiao, Chang-Fu Peng, Han-Wu Deng
European Journal of Pharmacology 311(1996)163-167,-0001,():
-1年11月30日
Our previous work has suggested that the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) can abolish the protective effect of ischemic preconditioning in the isolated rat heart. Therefore we tested the hypothesis that CGRP- or capsaicin-induced preconditioning protects against ischemia-reperfusion injury in the isolated perfused rat heart. Thirty minutes of global ischemia and 30 min of reperfusion caused a significant cardiac contractile dysfunction, ventricular arrhythmia, and an increased release of creatine phosphate kinase. Pretreatment with CGRP or capsaicin, which evokes release of CGRP from cardiac sensory nerves, for 5 min produced a significant improvement of cardiac function, a reduction in the incidence of ventricular arrhythmia, and a decrease in the release of creatine phosphate kinase. However, the cardioprotection provided by CGRP- or capsaicin-induced preconditioning was abolished by CGRP-(8-37) and ruthenium red, respectively. These findings suggest that CGRP- or capsaicin-induced preconditioning protects against ischemic myocardial injury. The present results also suggest that CGRP may be an endogenous myocardial protective substance in the rat.
Heart,, rat, Preconditioning, CGRP (, calcitonin gene-related peptide), , CGRP-(, 8-37), , Capsaicin, Ruthenium red
-
52浏览
-
0点赞
-
0收藏
-
0分享
-
47下载
-
0评论
-
引用
肖洲生, 周宏灏
中国药理学通报,2001,17(4):365~368,-0001,():
-1年11月30日
Cbrαl基因编码一个成骨细胞特异性转录因子,调控成骨细胞发育、分化和骨的形成。Cbrαl基因含9个外显子,但它的多个外显子存在选择性剪接,产生多样Cbrαl的异构体,具有不同的转录激活潜能。多条信号传导通路如RasMAPK、cAMP、Smads DPC4通路等涉及到Cbrαl的活性或表达的调控。这些研究为药物调控成骨细胞分化和骨的形成及基因治疗骨质疏松症开拓新的思路。
Cbrαl基因, 成骨细胞分化, 信号传导通路, 表达调控
-
53浏览
-
0点赞
-
0收藏
-
0分享
-
70下载
-
0评论
-
引用