BBS Faculty Member - Kun Ping Lu

Kun Ping Lu

Department of Medicine

Beth Israel Deaconess Med. Ctr.
Center for Life Science, Room 0408
3 Blackfan Circle
Boston, MA 02115
Tel: 617-735-2016
Fax: 617-735-2050
Email: klu@bidmc.harvard.edu
Lab Members: 5 postdoctoral fellows, 1 graduate student
Visit my lab page here.



My laboratory has pioneered in elucidating the role of protein conformational regulation after proline-directed phosphorylation in cell signaling in health and disease, and also identified promising novel targeted therapies for treating cancer, autoimmune disorders, traumatic brain injury and Alzheimer’s disease.

Protein phosphorylation regulates diverse cellular processes in health and disease. Our lab has discovered a unique enzyme called Pin1 that introduces a pivotal new twist in phosphorylation signaling by converting phosphorylated proteins between two functionally distinct conformations,
cis and trans. Deregulation of this novel signaling mechanism leads to accumulation of proteins in the pathogenic conformations, thereby having profound impact on the development of many diseases, especially those related to aging or stress such as Alzheimer’s disease, traumatic brain injury, cancer and autoimmune disorders. More significantly, our lab has recently developed innovative antibody technology that can specifically detect and eliminate these pathogenic conformations, such as cis tau protein for early diagnosis and treatment of brain injury and Alzheimer’s disease. By developing high-throughput drug screens, we have also identified Pin1 small molecular inhibitors that potently block multiple disease-driving pathways in cancer, asthma and lupus. These discoveries have suggested a promising new paradigm for the development of diagnostics and therapeutics that specifically target the pathogenic protein conformations in a wide range of diseases.

The current projects focus on translating our new discoveries into clinical products for improving human health, notably Pin1 inhibitors to stop multiple cancer-driving pathways and conformation-specific antibody for early diagnosis and treatment of Alzheimer’s disease and traumatic brain injury.



Last Update: 7/27/2015



Publications

For a complete listing of publications click here.

 


 

Zhou, X. Z., Huang P., Lee, T. H., Shi, R., Lu, G., Bronson, R. and Lu, K. P . 2011, The telomerase inhibitor PinX1 is a major haploinsufficent tumor suppressor essential for chromosome stability in mice. J. Clin. Invest . 121: 1266-1282 (The Cover Story).

Nakamura, K., Greenwood, A., Binder, L., Bigio, E. H., Denial, S. J., Nicholson, L., Zhou, X. Z. and Lu, K. P . 2012. Proline isomer-specific antibodies reveal the early pathogenic tau conformation in Alzheimer's disease.
Cell 149 : 232-244.

Luo, M. L., Gong, C., Chen, C. H., Hu, H., Huang, P., Zheng, M., Yao, Y., Wei, S., Guo, W., Reinhard, F., Wulf, G., Lieberman, J., Zhou, X. Z., Song, E. and Lu, K. P. 2014, Prolyl isomerase Pin1 acts downstream of miR-200 to promote cancer stem-like cell traits in breast cancer.
Cancer Res 74: 3603-3616.

Wei, S., Kozono, S., Kats, L., Li, W., Nechama, M., Li, W., Guarnerio, J., Bozkurt, G., Luo, M., You, M. H., Yao, Y. Kondo, A., Hu, H., Moerke, N. J., Cao, S., Reschke, M., Rego, E. M., LoCoco, F., Cantley, L., Lee, T. H., Wu, H., Zhang, Y., Pandolfi, P. P., Zhou, X. Z., and Lu, K. P. 2014, Active Pin1 as a target of ATRA in acute promyelocytic leukemia and breast cancer.
Nature Med. 21: 457-466.

Kondo, A., Shahpasand, K., Mannix, R., Qiu, J., Moncaster, J., Chen, C. H., Yao, Y., Lin, Y. M., Driver, J. A., Sun, Y., Wei, S., Luo, M. L., Albayram, O., Huang, P., Rotenberg, A., Ryo, A., Goldstein, L. E., Pascual-Leone, A., Mckee, A., Meehan, M., Zhou, X. Z., and Lu, K. P. 2015, Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy.
Nature 523: 431-436 (Research Article).



© 2015 by the President and Fellows of Harvard College