李夏璐博士 - 科学研究 - 北京生命科学研究所

李夏璐博士

北京生命科学研究所研究员

Xialu Li, Ph.D.
Assistant Investigator, NIBS, Beijing, China

教育经历

Education

2000	中国科学院上海生物化学研究所分子生物学博士
	Ph.D. degree in molecular biology Shanghai Institute of Biochemistry, Chinese AcademyofSciences, P.R.China
1995	复旦大学生物化学系生物化学学士
	B.S.degree in Biochemistry Department of Biochemistry, Fu-Dan University, Shanghai, P. R. China

工作经历

Professional Experience

June 2006-2014	北京生命科学研究所研究员
	National Institute of Biological Sciences, Beijing,China
2005-June 2006	美国哥伦比亚大学生物系助理研究员
	Associate Research Scientist
2000-2005	美国哥伦比亚大学生物系博士后
	Post-Doctoral Research Scientist Department of Biological Sciences,Columbia UniversityU.S.A.

研究概述：

转录是生命不可或缺的重要生物学过程。然而，在过去的三十年中，越来越多的实验证据表明，转录也是生物体内引起基因组非稳性的主要原因之一。本实验室的主要研究兴趣在于运用遗传学，分子生物学，生物化学和生物信息学等方法，研究与转录相关的基因组非稳性，并探索这一机制的潜在病理意义。目前，我们的工作集中于：

1. R loop与基因组非稳性: R loop是一种在转录过程中产生的由新生RNA链与模板DNA链配对形成的RNA:DNA杂合分子。我们之前的研究工作揭示，从细菌到人类细胞，这种RNA：DNA杂合分子的形成都会破坏基因组完整性。我们希望后续工作可以：

a．解析哺乳动物细胞预防和解除R-loop结构的机制

b．探究R-loop介导的基因组非稳性在人类疾病形成中的潜在的作用

2. 癌症基因组的进化：我们最近的一项研究结果表明转录失调可以导致人染色体特定区域稳定性下降。基因组非稳性和转录重编排与许多人类疾病密切相关，其中包括癌症。由上述工作引出的一个重要而有趣的问题是：转录是否在癌症基因组进化中扮演了重要但是尚未了解的角色。目前我们正在探索转录相关基因组非稳性在卵巢癌基因组变化中的作用。

Research Description:

Transcription is a fundamental and ineluctable process of life. However, in the past three decades, a considerable body of evidence has established that transcription is one of the key contributors to genome instability. The main research goal of our lab is to understand molecular mechanism(s) and pathological relevance(s) of transcription-associated genome instability in mammalian cells by using a variety of genetic, molecular, biochemical and bioinformatic approaches. Our current interests focus on:

1. R loop and genome instability: Cotranscriptionl R loop is a structure in which a nascent transcript is hybridized with the template DNA strand, leaving the non-template strand unpaired. Our previous studies have established that such RNA:DNA hybrid has an inherent impact on the integrity of the genome from bacteria to mammals. We are currently interested to:

a. elucidate the mechanism(s) underlying R loop-mediated genome instability

b. dissect the mechanism(s) by which mammalian cells prevent and resolve R loop during transcription

c. investigate the pathological consequence(s) of transcriptional R loop formation

2. Cancer genome evolution: One of our recent studies has established a striking link between transcription disorder and the expression of chromosome fragility in human cells. Gross chromosome abnormality and transcription reprogramming are hallmarks of a number of human diseases, including cancer. Extending from the above study, we are currently pursuing the potential role(s) of transcription-associated genome instability in ovarian cancer genome evolution.

1. Yi Wei*, Fan Yang*, Jie Liu, Yonggong Zhai and Xialu Li, R loop underlies transcription-associated chromosome fragility in human cells (*These authors contribute equally) (in preparation)

2. Wenjian Gan, Zhishuang Guan and Xialu Li, Impairment of replication fork progression is an evolutionally conserved mechanism underlying R loop-mediated genome instability. (in preparation)

3. Xialu Li and James L. Manley, 2009, The Role of Alternative Splicing During the Cell Cycle and Programmed Cell Death. In Ralph A. Bradshaw and Edward A. Dennis, editors: Handbook of Cell Signaling 2nd edition, Oxford:Academic Press, , pp. 2329-2334. (invited book chapter)

4. Xialu Li*, Tianhui Niu., and James L Manley. 2007. The RNA binding protein RNPS1 alleviates ASF/SF2 depletion-induced genomic instability. RNA 13(12): 2108-2115 (*corresponding author).

5. Xialu Li and James L Manley, 2006, Co-transcriptional processes and their influence on genome stability. Genes & Development, 2006; 20(14):1838-1847.

6. Xialu Li and James L Manley. 2006. Alternative Splicing and Control of Apoptotic DNA Fragmentation. Cell Cycle 5(12).1286-1288

7. Xialu Li and James L. Manley, 2005, New talents for an old acquaintance: the SR protein splicing factor ASF/SF2 functions in the maintenance of genome stability. Cell cycle, 4(12): 1706-1708.

8. Xialu Li, Jin Wang and James L Manley, 2005, Loss of splicing factor ASF/SF2 induces G2 cell-cycle arrest and apoptosis, but inhibits internucleosomal DNA fragmentation, Genes & Development, 19(22):2705-2714.

9. Xialu Li and James L Manley, 2005, Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell, 122 (3), p365-378.

10. Boliang Li, Xialu Li et al., 1999, Human acyl-CoA:Cholesterol acyltransferase-1 (ACAT-1) gene organization and evidence that the 4.3-kilobase ACAT-1 mRNA is produced from two different chromosomes., J Biol Chem, 274 (16): p11060-11071