Download 摘要： 卢坤平，现任美国哈佛大学医学院副教授、Beth Israel

摘要：
卢坤平，现任美国哈佛大学医学院副教授、Beth Israel Deaconess 医学中
心医学部 Ping Lu 实验室负责人，美国国立卫生研究院、中国国家自然科学基金
委、哈佛大学 Beth Israel Deaconess 医学中心等五个专业委员会会委员；
《Nature》、《EMBO》等数十个国际著名科技期刊审稿人。2005 年被聘为南方
医科大学生物化学与分子生物学专业特聘教授，并推荐为 2005 年长江学者讲座
教授。获得各项研究经费 980 万美元。发现了一个以个人名字命名的重要基因家
族（pin 1, 2..X）及其表达产物，并在此基础上，研究了细胞周期调节及端粒
酶调控的分子机制，为阐明 Pin 系列蛋白质与癌症以及 Alzheimer 病的重要关系
做出贡献。发现了 Pin 系列蛋白质在肿瘤和衰老过程中的重要作用。所取得的原
创性突破得到学术界公认，先后在 SCI 收录的高影响因子期刊上共发表论文 52
篇，其中《Cell》3 篇，《Nature》7 篇，《Science》2 篇。申请美国专利 11
项，其中 2 项已获得授权。
Dr. Kun Ping Lu Associate Professor Harvard Medical School Department of
Medicine Beth Israel Deaconess Medical Center Harvard Institutes of
Medicine, Room 1047 77 Avenue Louis Pasteur Boston, MA 02115 Tel: (617)
667-4143 Fax: (617) 667-06
Dr. Kun Ping Lu Associate Professor
Harvard Medical School
Department of Medicine
Beth Israel Deaconess Medical Center
Harvard Institutes of Medicine, Room 1047
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: (617) 667-4143
Fax: (617) 667-0610
Email: [email protected]
lab:
http://www.research.bidmc.harvard.edu/HemOnc/PingLab/index.htm
Education:
1979-1984 M.D. Fujian Medical College (P. R. China)
1984-1987 M.Sc. (Pharmacology) Suzhou Medical College (P. R. China)
1989-1992 Ph.D. (Cell Biology) Duke University
Postdoctoral Training:
1993-1996 Research Associate, Molecular Biology, Salk Institute
Field Of Research:
Cell Cycle Control and Tumorigenesis
Research Interest:
Cell proliferation is regulated by several control points, termed checkpoints, and
deregulation of these checkpoints may lead to cancer. Protein phosphorylation by the
mitotic kinase Cdc2, mainly on Ser/Thr-Pro motifs, plays an essential role in triggering
a programmed set of mitotic events. We have recently cloned two novel genes, Pini and
Pin2, involved in mitotic regulation. Pini is a novel and conserved peptidyl-prolyl
isomerase that specifically catalyzes prolyl isomerization of the phosphorylated
Ser/Thr-Pro bond and is the only PPIase documented to be essential for cell survival.
Pini uses its N-terminal WW domain, a novel phosphoserine-binding module, to interact
with a defined subset of mitosis-specific phosphoproteins, including Cdc2 regulators
and substrates. Furthermore, Pini regulates the activity of phosphoproteins and controls
the timing of mitotic entry, presumably by phosphorylation-dependent prolyl
isomerization. Thus, Pini is a novel post-phosphorylation regulator. Pin2 is a major
expressed product of the Pin2/TRF1 gene, which regulates maintenance of telomeres.
Telomeres are genetic elements that are essential for preserving chromosome integrity
and are implicated in mitotic checkpoint control. Interestingly, Pin2 is also involved
in regulation of mitosis. Pin2 interacts with and is also phosphorylated by the ATM
protein kinase, encoded by the gene responsible for the human genetic disorder ataxia
telangiectasia. This autosomal recessive disorder displays a wide range of abnormalities,
including genomic instability, cell cycle checkpoint defects and predisposition to
cancer and aging, which are believed to be related to telomere dysfunction. Based on
the above findings, we hypothesize that Pini and Pin2 play critical roles in coordinating
telomere maintenance and cell division, whose aberrations contribute to oncogenesis.
To test this hypothesis, we will :
1. elucidate the molecular mechanism of Pin 1-dependent mitotic regulation,
2. determine the role of the Pin2 and ATM interaction in regulating the cell cycle
and telomere maintenance, and
3. evaluate the role of Pin 1 and Pin2 in cancer. These studies should help us
understand the molecular mechanisms underlying control of the cell cycle and
oncogenesis, and may eventually lead to the development of new therapeutic
reagents