The long-term goals of the Li laboratory are to identify and characterize novel molecular mechanisms that regulate cellular stress response and cell death signaling. We hope that our study will shed light on novel therapeutic targets for treatment of human diseases, such as cancer and neurodegenerative diseases.
College:
09/1983-07/1988 University of Science & Technology of China,Hefei, Anhui, China
B.Sc. Biology
Graduate School:
09/1989-12/1994 Dept. of Biological Sciences, Wayne State University, Detroit, MI,
USA
PhD Biology, Mentor: Dr. Allan Nicolson
Post-doctoral training:
02/1995-03/2000 Dept. of Cell Biology, Harvard Medical School, Boston, MA, USA
Postdoc fellow
NIGMS R01 "Functional study of C53 protein as a novel regulator of checkpoint kinases"
1. C53/LZAP: A putative tumor suppressor that regulates DNA damage checkpoint signaling and NF-kB transcriptional activity.
C53 (also known as Cdk5rap3 and LZAP) is a highly conserved protein, and its orthologues are found in vertebrate, invertebrate and plants but not in yeast and bacteria. We originally reported that C53/LZAP protein sensitized cancer cells to DNA damage-induced cell death by modulating the G2/M checkpoint (Jiang et al, 2005). Subsequently, it was reported that C53/LZAP functioned as a tumor suppressor via inhibiting NF-kB transcriptional activity. Our research aims to further characterize its roles in signal transduction, animal development and disease pathogenesis, and to elucidate the molecular mechanism of its action.
2. RCAD/KIAA0776: A novel C53/LZAP-binding protein that regulates protein stability of C53/LZAP and NF-kB signaling
To further dissect the molecular mechanism of C53/LZAP function, we attempted to identify potential C53/LZAP interactors. We have identified a novel C53/LZAP-binding protein RCAD (Regulator of C53/LZAP and DDRGK1) that plays a critical role in regulation of C53/LZAP protein stability (Wu et al, 2010). Our future study aims to investigate the role of RCAD in C53/LZAP-mediated signaling pathways, its potential involvement in cancer biology as well as underlying biochemical and molecular mechanisms of RCAD's function.
3. The Ufm1 conjugation system: a novel ubiquitin-like system.
Protein modifications by Ubiquitin (Ub) and Ubiquitin-like protein modifiers (Ubls) play crucial roles in many cellular processes such as transcription, signal transduction and cell cycle progression. Human Ubiquitin-fold modifier 1 (UFM1) is a newly identified Ubl with 85 amino acid residues. Like some of other Ubls, Ufm1 is conjugated to other targets through a series of enzymatic reactions. The process of protein modification by Ufm1 was termed as "Ufmylation". Yet the physiological targets and biological functions of the UFM1 conjugation system remain largely unknown. Interestingly, our results indicated that C53/LZAP and its binding partner RCAD are involved in the Ufm1-mediation protein modification. Our research aims to identify the physiological targets of the Ufm1 conjugation systems, and to elucidate its biological functions in animal development and cell signal transduction. Furthermore, we will investigate the biochemical role of C53/LZAP and RCAD proteins in the Ufm1-mediated conjugation.
Li, H. and Nicholson, A. W. (1996) Defining the enzyme binding domain of a ribonuclease III processing signal. Ethylation interference and hydroxyl radical footprinting using catalytically inactive RNase III mutants. EMBO J. 15, 1421-1433.
Shi, L., Chen, G., MacDonald, G., Bergeron, L., Li, H., Miura, M., Rotello, R. J., Miller, D. K., Li, P., Seshadri, T., Yuan, J., Greenberg, A. H. (1996) Activation of an interleukin 1 converting enzyme-dependent apoptosis pathway by granzyme B. Proc. Natl. Acad. Sci. USA 93, 11002-11007.
Cryns, V. L., Bergeron, L., Zhu, H., Li, H., Yuan, J. (1996) Specific cleavage of alpha-fodrin during Fas- and tumor necrosis factor-induced apoptosis is mediated by an interleukin-1beta-converting enzyme/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease. J. Biol. Chem. 271, 31277-31282.
Li, H., Bergeron, L., Cryns, V., Pasternack, M. S., Zhu, H., Shi, L., Greenberg, A., Yuan, J. (1997) Activation of caspase-2 in apoptosis. J. Biol. Chem. 272, 21010-21017.
Haviv, R., Lindenboim, L., Li, H., Yuan, J., Stein, R. (1997) Need for caspases in apoptosis of trophic factor-deprived PC12 cells. J. Neurosci. Res. 50, 69-80.
Zhou, B-B., Li, H., Yuan, J., Kirschner, M. W. (1998) Caspase-dependent activation of cyclin-dependent kinases during Fas-induced apoptosis in Jurkat cells. Proc. Natl. Acad. Sci. USA 95, 6786-6790.
Li, H., Zhu, H., Xu, C., Yuan, J. (1998) Cleavage of BID by caspase-8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell94, 491-501.
Chou, J. J., Li, H., Salvesen, G., Yuan, J. and Wagner, G. (1999) Solution structure of Bid, an intracellular amplifier of apoptotic signaling. Cell 96, 615-624
Li, H. and Yuan, J. (1999) Deciphering the pathways of life and death. Current Opinion in Cell Biology 11, 261-266.
Ruffolo, S. C., Breckenridge, D. G., Nguyen, M., Goping, I. S., Gross, A., Korsmeyer, S. J., Li, H., Yuan, J., Shore, G. C. (2000) BID-dependent and BID-independent pathways for BAX insertion into mitochondria. Cell Death Differ 7, 1101-1108.
Tong, X. and Li, H. (2004) eNOS protects from prostate cancer cells from TRAIL-induced apoptosis. Cancer Letters 210, 63-71.
Fu, T., Blei, A.T., Takamura, N., Lin, T., Guo, D., Li, H., O'Gorman, M.R., Soriano, H.E. (2004)Hypothermia inhibits Fas-mediated apoptosis of primary mouse hepatocytes in culture. Cell Transplant 13, 667-676.
Wu, J., Luo, S., Hai, J., Li, H. (2005) Mammalian CHORD-containing protein 1 is a novel heat shock protein 90-interacting protein. FEBS letters 579, 421-426.
Jiang, H., Luo, S., Li, H. (2005) Cdk5 activator binding protein C53 regulates apoptosis induced by genotoxic stress via modulating cyclin B1 phosphorylation. J. Biol. Chem. 280, 20651-20659
Yang, W., Monroe, J. Zhang, Y., George, D., Bremer, E, Li, H. (2006) Proteasome inhibition induces both pro-and anti-cell death pathways in prostate cancer cells. Cancer Letters 243, 217-227.
Zhao, Y., Fedczyna, T. O., McVicker, V., Caliendo, J., Li, H., Pachman, L. M. (2007) Apoptosis in the skeletal muscle of untreated children with juvenile dermatomyositis: Impact of duration of untreated disease. Clin Immunol 125, 165-172.
Jiang, H., Wu, J., He, C., Yang, W., Li, H. (2009) A tumor suppressor C53 protein antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation. Cell Research 19, 458-468.
Wu, J., Lei, G., Mei, M, Li, H. (2010) A novel C53/LZAP-interacting protein regulates C53/LZAP stability and NF-kB signaling. J. Biol. Chem. 285, 15126-15136.
Zhu, S., Zhang, J., Bai, G., Li, H. (2011) Necrostatin-1 ameliorates symptoms in R6/2 transgenic mouse model of Huntington's disease. Cell Death and Diseases 2, e115.
