Since joining in UNMC in 2006 as associate professor, Dr. David Wan-Cheng Li has received two NIH/NEI R01 grants and also several non-NIH external grants to support his research and published over thirty peer-reviewed research articles during this period.  He received the outstanding cataract research award from the National Foundation for Eye Research in 2006, and the Lotus Scholar Contribution Award from Hunan Province Government, China in 2009.  Dr. Li has been invited as reviewer over forty major international biomedical journals, and grants for different organizations. He served as editor, associate editor and editorial board members for various biomedical journals.  He has also served as organizer or co-organizer for dozens of national and international symposia or conference sessions.  He has trained half dozen postdoctoral fellows and more than a dozen Ph.D. students since he served as faculty member.  Research in Dr. David W. Li’s laboratory focuses on the molecular and cellular mechanisms of ocular development and diseases, and cancer. Currently, Li lab has been concentrated on the following projects.

Project 1.  Functional Mechanisms of Protein Serine/Threonine Phosphatases in Lens. (Grants Support: EY11372 1996-2002, $598,561; EY015765 2005-2010, $872,574; and Pending).

In 1995, we first proposed that stress-induced apoptosis of lens epithelial cells act as a common cellular mechanism for non-congenital cataract formation in human and other vertebrates. Since our initial work, about seven hundred research articles have been published on lens epithelial cell apoptosis and cataractogenesis from many laboratories over the world.

For this project, the first grant (EY11372) received from NIH/NEI supported following important discoveries:

  1. The regulatory components mediating apoptotic pathway in the ocular lens system including p53, Bax, Caspase-3;
  2. Protein serine/threonine phosphatase-1 (PP-1) is a major phosphatase in the ocular lens, preventing stress-induced apoptosis by oxidative stress and other stress conditions;
  3. Among the three major MAP kinases (ERK1/2, JNK1/2 and p38 kinases), expression and activities of ERK1/2 are very high in both young lens and old human lenses, in both lens epithelium and lens fiber cells;
  4. We first demonstrate that the human telomerase catalytic subunit can form functional complexes with the RNA template from rabbit and bovine;
  5. Besides the classical role of synthesizing telomere, telomerase can negatively regulate apoptosis, accelerate cell growth via RB-E2F pathway, and suppress lens cell differentiation through the modulation of the RAS/RAF/MEK/ERK signaling pathway;
  6. We demonstrate that the anti-proapoptotic gene, Bcl-2, can regulate gene expression through control of the RAS/RAF/MEK/ERK signaling pathway; By repressing expression of aB-crystallin, Bcl-2 lost its anti-apoptotic function;
  7. For the first time, we demonstrate that the two a-crystallins display differential abilities to regulate different signal transduction pathways and prevent stress-induced apoptosis;
  8. Oxidative stress regulates c-Jun, c-fos and c-myc in lens system to control other genes in the lens, which partially contributes to cataractogenesis.

These results are published in 12 research articles and 2 review articles:

Mao YW, Liu JP, Xiang H, Li DW. (2004). Human aA- and aB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis. Cell Death Differ. 11(5):512-26. PMID: 14752512

Feng H, Xiang H, Mao YW, Wang J, Liu JP, Huang XQ, Liu Y, Liu SJ, Luo C, Zhang XJ, Liu Y, Li DW. (2004). Human Bcl-2 activates ERK signaling pathway to regulate activating protein-1, lens epithelium-derived growth factor and downstream genes. Oncogene. 23(44):7310-7321. PMID: 15326476

Liu JP, Schlosser R, Ma WY, Dong Z, Feng H, Liu L, Huang XQ, Liu Y, Li DW. (2004). Human aA- and aB-crystallins prevent UVA-induced apoptosis through regulation of PKCa, RAF/MEK/ERK and AKT signaling pathways. Exp Eye Res. 79(3):393-403. Erratum in: Exp Eye Res.79(6):807. Corrected and republished in: Exp Eye Res. 79(6):393-403. PMID: 15669141

Li DW, Liu JP, Wang J, Mao YW, Hou LH. (2003). Expression and activity of the signaling molecules for mitogen-activated protein kinase pathways in human, bovine, and rat lenses. Invest Ophthalmol Vis Sci.44(12):5277-86. PMID: 14638727.

Xiang H, Wang J, Mao Y, Liu M, Reddy VN, Li DW. (2002). Human telomerase accelerates growth of lens epithelial cells through regulation of the genes mediating RB/E2F pathway. Oncogene. 21(23):3784-3791. PMID: 12032846.

Geissler FT, Li DW, James ER. (2001). Inhibition of lens epithelial cell growth by induction of apoptosis: potential for prevention of posterior capsule opacification. J Ocul Pharmacol Ther. 17(6):587-96. PMID: 11777182.

Li DW, Xiang H, Fass U, Zhang XY.(2001). Analysis of expression patterns of protein phosphatase-1 and phosphatase-2A in rat and bovine lenses. Invest Ophthalmol Vis Sci.42(11):2603-9. PMID: 11581206.

Li DW, Xiang H, Mao YW, Wang J, Fass U, Zhang XY, Xu C. (2001). Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis. Exp Cell Res. 266(2):279-91.PMID: 11399056.

Mao YW, Xiang H, Wang J, Korsmeyer S, Reddan J, Li DW. (2001). Human bcl-2 gene attenuates the ability of rabbit lens epithelial cells against H2O2-induced apoptosis through down-regulation of the alpha B-crystallin gene. J Biol Chem. 276(46):43435-45.PMID: 11546795.

Xiang H, Wang J, Mao YW, Li DW. (2000). hTERT can function with rabbit telomerase RNA: regulation of gene expression and attenuation of apoptosis. Biochem Biophys Res Commun. 278(3):503-510. PMID: 11095941.

Li DW, Fass U, Huizar I, Spector A. (1998). Okadaic acid-induced lens epithelial cell apoptosis requires inhibition of phosphatase-1 and is associated with induction of gene expression including p53 and bax. Eur J Biochem. 257(2):351-61. PMID: 9826180.

Li DW, Spector A. (1997). Hydrogen peroxide-induced expression of the proto-oncogenes, c-jun, c-fos and c-myc in rabbit lens epithelial cells. Mol Cell Biochem. 173(1-2):59-69. PMID: 9278255

Spector, A., Ho, Y-S., Wang, R-R., Ma, W., Yang, Y. and Li, W-C. (1998) Evaluation of the antiperoxide defense system of the lenses utilizing GSH peroxidase transgenics and knockouts. In Oxidative Stress and Redox Regulation: Cellular Signaling, AIDS, Cancer and Other Diseases. (Montagnier, Olivier and Pasquier, eds). Chapter 48, pp507-515. Marcel Dekker, Inc., New York . (review article).

Li, D. W-C. (1997). The lens epithelium, apoptosis and cataract formation. In Eye Lens Epithelium: Damaging Mechanisms and Lens Transparency. (Glaesser D, Hockwin O and Vrensen GF, eds). Chapter 8, pp81-108. Deutsche Akademic der Naturforscher Leopoldina (German Academy of Natural Sciences), Halle . Nova Acta Leopoldina. NF 75, Nr. 299, 81-108. ISSN 0369-5034. (review article).

The ongoing research on this project was subsequently funded by the second NIH/NEI grant (EY015765), which allowed us to make the following significant discoveries:

  1. The protein serine/threonine phosphatase-1 directly dephosphorylates p53 at Ser- 15, Ser-20, Ser-37 and Ser-46, and other sites to prevent stress-induced apoptosis;
  2. Dephosphorylation of p53 at these sites substantially changes its transcriptional activity and proapoptotic ability;
  3. We demonstrated for the first time that p53 directly regulates Bak expression to control apoptosis of human lens epithelial cells, and modulation of p53 phosphorylation status by PP-1 affects p53 control of apoptosis through regulation of Bak;
  4. The p53-Bak pathway is also involved in control of differentiation of lens epithelial cells through regulation of the p53 stability.
  5. Dephosphorylation of p53 at a single residue by PP-1 changes the global expression pattern of more than 80 p53 downstream target genes;
  6. We first demonstrate that p53 directly regulates c-Maf and Prox1, two important transcription factors for lens development to control lens differentiation;
  7. We show that p53 directly regulates lens crystallin genes to control lens differentiation;
  8. The protein serine/threonine phosphatase-2A also directly dephosphorylates p53 at Ser-15 to modulate p53-Bak pathway;
  9. We elucidated, for the first time, the molecular mechanism why the ocular lens does not develop natural tumor;
  10. We demonstrated that PP-1 directly dephosphorylates Pax-6, an important transcription factor controlling brain and eye development; dephosphorylation of Pax-6 by PP-1 significantly modulates Pax-6 function;
  11. We also demonstrate that PP-1 is one the major phosphatases that regulate AKT kinase activity to modulate lens proliferation, differentiation and apoptosis.
  12. We first demonstrate that sumoylation plays an important role in regulating lens differentiation.

These results are published over 2 dozens of research articles and several review articles:

Xiukun Cui, Lei Wang, Jing Zhang, Rong Du, Shengjie Liao, Duanzhuo Li, Chang Li, Tie Ke, David Wan-Cheng Li , Hua Huang, Zhan Yin,  Zhaohui Tang,  Mugen Liu (2013). HSF4 regulates DLAD expression and promotes lens de-nucleation. Biochim  Biophy Acta-Molecular Basis of Diseases1832:1167-1172. 

Weike Ji, Xiangcheng Tang,  Min Yi, Peichao Chen, Fang-Yuan Liu, Xiao-Hui Hu, Wenfeng Hu, Shujun Fu, Jifang Liu, Kaili Wu, Minxing Wu, Xialin Liu, Lixia Luo, Shan Huang, Zhenzhen Liu, Minbin Yu, Yi-Zhi Liu and David W-C Li (2013). p53 directly Regulates aA-, and bA3/A1-Crystallin Genes to Modulate Lens Differentiation. Curr. Mol. Med. 13(6): 968-978. 

Ling Li, Ling Wang, Tingting Li, Xi Li, Xiaoqin Huang, Xiao-Wen Chen, Zili Li, Xiangmin Lv,  Fang-Yuan Liu, Zhong-Wen Luo, Mugen Liu, Xiao-Hui Hu, Wen-Feng Hu, Zhao-Xia Huang, Ming Yi, Shao-Jun Liu, Yi-Zhi Liu, and David W. Li. (2013). ERK signaling pathway regulates embryonic survival and eye development in goldfish, Carassius auratus.  Curr. Mol. Med. 13(6): 959-967. 

Huang Xiao-Qin, Zhao-Xia Huang, Zili Li, Xiao-Wen Chen, Xi Li, Xiang-Cheng Tang, Fang-Yuan Liu, Yan Liu, Lili Chen, Wen-Jun Han, Long Liu, Kai-Li Wu, Ming-Xing Wu, Xia-Lin Liu, Li-Xia Luo, Min-Bin Yu, Yi-Zhi Liu, Shaojun Liu and David W. Li (2013). C-Jun terminal kinases play an important role in regulating embryonic survival and eye development in vertebrates.   Curr. Mol. Med. 13(1): 228-237. 

Wen-Bin Liu, Qin Yan, Fangyuan Liu, Xiangcheng Tang, He-Ge Chen, Jiao Liu, Nie Lei, Xu-Wen Zhang, Weike Ji, Xiao-Hui Hu, Wenfeng Hu, Zachary Woodward, Kaili Wu, Mingxing Wu, Xialin Liu, Lixia Luo, Minbin Yu, Yizhi Liu, Shao-Jun Liu, and David Wan-Cheng Li (2012). Protein Serine/Threonine Phosphotase-1 Is Essential in Governing Normal Development of Vertebrate Eye.  Curr. Mol. Med. 12(10): 1361-1371. 

M. Deng, P. Chen., F. Liu., S. Fu., H. Tang., Y. Fu., Z. Xiong., S. Hui., W. Ji., X. Zhang., L. Zhang., L. Gong., X. Xu., W. Hu., S. Sun., J. Liu., L. Xiao., W.-B. Liu., Y.-M. Xiao., S. –J. Liu, Y. Liu and D. W.-C. Li (2012). The p53-Bak Apoptotic Signaling  Axis Plays An Essential Role in Regulating Differentiation of the Ocular Lens.  Curr. Mol. Med.  12(8): 901-916. 

Fangyuan Liu, Xiang-Cheng Tang, Mi Deng, Weike Ji, Xinyan Zhang, Lili Gong, Jiao Liu, Lan Zhang4 Shuming Sun, Kaili Wu, Ming-Xing Wu, Xia-Lin Liu, Ming-Bin Yu, Yizhi Liu, and David W-C Li. (2012). The Tumor Suppressor p53 directly Regulates c-Maf and Prox-1 to Control Lens Differentiation. Curr. Mol. Med.  12(8):917-928. 

J Liu, WK Ji, SM Sun, L Zhang, H-G Chen, Y Mao, L Liu, X Zhang, L Gong, M Deng, L Chen, W-J Han, P-C Chen, W-F Hu, XH Hu, JP Liu, Z Woodward, W-B Liu,  Y-M Xiao, S-P Liang, Yun Liu S-J Liu and D W-C Li  (2012) The PP2A-Ab Gene Is Regulated by Multiple Transcriptional Factors Including Ets-1, SP1/SP3, and RXRa/b. Curr. Mol. Med.  12(8): 982-994.

Cui X, Zhang J, Du R, Wang L, Archacki S, Zhang Y, Yuan M, Ke T, Li H, Li D, Li C,  Li DW, Tang Z, Yin Zand Liu M. (2012). HSF4 is involved in DNA damage repair and cataract formation via regulation of rad51.  Biochim  Biophy Acta 1822(8):1308-1315.  PMID:22587838.

Mitchell DC, Brad BA, Liu L, Hu X-H, Huang X-Q,  Ji W-K, Chen P-C, Hu W-F, Liu J-P, Liu, Zhang J, Liu M, Li DW-C (2011). GEFT, a rho family guanine nucleotide exchange factor regulates lens differentiation in vertebrate eye. Curr. Mol. Med. 11(6): 465-480. 

Zhang L, Sun S, Zhou J, Liu J, Lv JH, Yu XQ, Li C, Gong L, Yan Q, Deng M, Xiao L, Ma H, Liu JP, Peng YL,Wang D, Liao GP, Zou LJ, Liu WB, Xiao YM, Li DW. (2011). Knockdown of Akt1 Promotes Akt2 Upregulation and Resistance to Oxidative Stress-Induced Apoptosis through Control of Multiple Signaling Pathways. Antioxid Redox Signal. 15(1):1-16.  PMID: 21303257

Yan Q, Gong L, Deng M, Zhang L, Sun S, Liu J, Ma H, Yuan D, Chen PC, Hu X, Liu J, Qin J, Xiao L, Huang XQ, Zhang J, Li DW. (2010). Sumoylation activates the transcriptional activity of Pax-6, an important transcription factor for eye and brain development.  Proc Natl Acad Sci U S A. 107(49):21034-9. PMID: 21084637.

Xiao L, L Gong, D Yuan, M Deng, X-M Zeng, L Chen, L Zhang, Q Yan, J-P Liu, X-H Hu, S-M Sun, J Liu, H-L Ma, C-B Zheng, H Fu, P-C Chen, J-Q Zhao, S-S Xie, L–J Zou, Y-M Xiao, W-B Liu, J Zhang, Y Liu and Li, DW-C. (2010). Protein phosphatase-1 regulates Akt1 signaling transduction pathway to control gene expression, cell survival and lens differentiation. Cell Death & Differentiation. 17(9):1448-1462. PMID: 20186153.

Mi Deng, Pei-Chao Chen, Sisi Xie, Jun-Qiong Zhao, Lili Gong, Jinping Liu, Lan Zhang, Shuming Sun, Jiao Liu, Haili Ma, Surinder Batra, and Li, D.W.-C. (2010). The Small Heal Shock Protein αA-Crystallin Is Expressed In Pancreas and Acts as A Negative Regulator of Carcinogenesis. Biochem. Biophys. Acta.-Molecular Basis of Diseases. 1802:621-631. PMID: 20434541.

Chen H-G, W-J Han, M Deng, Qin J-C, J-P Liu, D Yuan, Liu J-P, Xiao L, Gong L, Liang S-P, Zhang J, Liu Y and Li D. W-C (2009). Transcriptional Regulation of PP2A-Aa is mediated by multiple factors including AP-2a, CREB, ETS, and SP-1. PLoS One. 4(9): e7019. PMID:19750005.

Ma H-L, Y-L Peng, L Gong, W-B Liu, S Sun, J Liu, C-B Zheng, H Fu, D Yuan, J-Q Zhao, P-C Chen, S-S Xie, X-M Zeng, Y-M Xiao, Y Liu and D W-C Li. (2009). The goldfish SG2NA gene encodes two a-type regulatory subunits for PP-2A and displays distinct developmental expression pattern. Gene Regulation & System Biol. 3:115-129. PMID: 19838339.

Qin J-C, He-Ge Chen, Qin Yan, Mi Deng, Liu J-P, S. Doerge, W-Y., Ma, Z. Dong, and Li, D. W-C. (2008). Protein phosphatase-2A is a target of epigallocatechin-3-gallate and modulates the p53-Bak apoptotic pathway. Cancer Res. 68(11):4150-4162. PMID: 18519674.

Liu, W-B, Y Li, L Zhang, H-G Chen, J-P Liu, S-M Sun, Yun Liu and Li, D. W-C (2008). Differential expression of the catalytic subunits for PP-1 and PP-2A and the regulatory subunits for PP–2A in mouse eye. Mol. Vis. 14:762-773. PMID: 18432318.

Yan Q, W-B Liu, J Qin, J-P Liu, H-G Chen, X Huang, L-L Chen, S-M Sun, M Deng, L-L Gong, Y Li, L Zhang, Y Liu, H Feng, Y-M Xiao, Y Liu, and Li DW-C. (2007). Protein Phosphatase-1 dephosphorylates Pax-6, a transcription factor controlling brain and eye development. J. Biol. Chem. 282 (19):13954-13965. PMID:17374606.

Mitchell DC, BA Bryan, J-P Liu, Liu WB, Zhang L, Qu J, Zhou X, Liu M, DW-C Li (2007). Developmental expression of three small GTPases in mouse eye. Mol. Vis. 13:1144-1153. PMID: 17653061.

Li, D. W-C., Liu Y, Liu J-P., P.C. Schmid., R. Schelosser, H. Feng, Y-M Xiao, W-B. Liu, Yan Q, Gong L, Sun S-M, Deng M, and Yun Liu (2006). Protein Serine/Threonine Phosphatase-1 Dephosphorylates p53 at Ser-15 and Ser-37 to Modulate its Transcriptional and Apoptotic Activities. Oncogene. 25:3006-3022. PMID: 16501611.

Wang J, Feng H, Huang X-Q, Xiang H, Y-W. Mao, Liu J-P, Yan Q, Liu W-B, Liu Y, Deng M, Gong L, Sun S-M, Yun Liu and Li, D. W-C. (2005). hTERT immortalizes bovine lens epithelial cells and suppresses differentiation through regulation of the ERK signaling pathway. J. Biol. Chem. 280: 22776-22787. PMID:15849192

Li, D. W-C., Liu, J-P., Mao Y. W., H. Xiang, J. Wang, W-Y Ma, Z. Dong, H. M. Pike, Rhoderick E. Brown and J. C., Reed (2005). Calcium-Activated RAF/MEK/ERK pathway mediates p53-dependent apoptosis and is abrogated by aB-crystallin through Inhibition of Ras Activation. Mol. Biol. Cell. 16:4437-4453. PMID:16000378

Li, D. W-C., L Gong, M Deng, J-P Liu, M Liu, and Y-W Mao (2010). The two lens structural proteins, aA- and aB-crystallins, prevent stress-induced apoptosis through regulation of multiple signaling transduction pathways.  In: Arrigo, Simon (eds). Small Stress Proteins and Human Diseases.  Nova Science Publisher, Inc NY, USA. Chapter 1.1 pp89-116. (review article).

Zhang L, Yan Q, Liu J-P, Zou L-J, Liu J, Sun S-M, Deng M, Gong L, Ji W-K, Li D W-C (2010). Apoptosis: Its Functions and Control in the Ocular Lens.  Curr. Mol. Med.  10(9):864-875. (review article).

Yan, Q., Mao Y-W and Li, D. W-C. (2009) Protein serine/threonine phosphatases in the nervous system. In: Binder, Hirokawa, Windhorst (eds). Encyclopedia of Neuroscience, Vol. 4. Springer, Heidelberg , pp 3325-3329. (review article).

Yan Q, Liu J-P, Li DW-C. (2006) Apoptosis in lens development and pathology. Differentiation. 74:195-211. (review article).

Currently, we are continuing to work on this project. Support on this project is pending. We are addressing the answers to the following questions regarding PP-1 control of lens differentiation and cataractogenesis in this project:

  1. How many residues in p53 are subjected to PP-1 regulation through dephosphorylation and how does dephosphorylation in these residues modulate p53 functions?
  2. How do p53 and other major lens transcription factors synergistically regulate lens genes to control lens differentiation?
  3. What are other major targets in the ocular lens that can be modulated by PP-1?

Project 2. Functional Mechanisms of Alpha-Crystallins (Grant Support: EY018380, 2009-2012, $1,028,456; and Pending).

The ocular lens is constantly exposed to stress conditions and thus lens epithelial cell apoptosis induced by stress factors is inevitable, the lens carries extremely efficient anti-apoptotic system to guard apoptosis. The lens structure proteins, aA- and aB-crystallins, are distinct anti-apoptotic regulators, which protect lens epithelial cells from apoptosis induced by a large number of stress factors as shown first by Dr. AP Arrigo's laboratory and later by many other laboratories including us. Although it is well established that the two a-crystallins are excellent anti-apoptotic regulators, the molecular mechanisms mediating their anti-apoptotic functions remains largely unknown.  The project supported by the above grant allows us to study the functional mechanisms of aA- and  aB-crystallins.  We have demonstrated that aA- and aB-crystallins can regulate apoptosis at multiple signaling steps and targets as summarized below:

  1. We demonstrated that aB-crystallin interacts with the procaspase-3 and partially processed procaspase-3 to repress caspase-3 activation;
  2. We revealed that a-crystallins can regulate the translocation of the proapoptotic members of the Bcl-2 family from cytoplasm into mitochondria to suppress apoptosis;
  3. We demonstrated that in response to UVA-induced apoptosis, aB-crystallin but not aA-crystallin can repress activation of the RAS/RAF/MEK/ERK signaling pathway to resist on the UVA and calcimycin-induced apoptosis;
  4. We showed that in response to UVA-induced apoptosis, aA-crystallin helps to activate the PI3K-AKT pathway to resist on the UVA-induced apoptosis;
  5. We demonstrated that a-crystallins interact with Caspase-3 and Bax in the developing lens to guard developmental apoptosis;
  6. We showed that aB-crystallin regulates GRF2 to control the RAS/RAF/MEK/ERK signaling pathway;
  7. We revealed that aA-crystallin is highly expressed in the pancreas besides its abundant expression in lens;
  8. We demonstrated that aA-crystallin negatively regulates carcinogenesis in pancreas;
  9. We showed that aA-crystallin can regulate TGF beta signaling pathway.

These results have been published in 10 research articles and 2 review articles:

Gong Lili et al. (2012). aA-crystallin negatively regulates p53-mediated intrinsic apoptotic pathway to enhance resistance of ocular pathogenesis.  Submitted.

Hu X-H et al.. (2012). Human alphaA- and alphaB-crystallins regulate DNA damaging signaling pathways to attenuate UVA-induced apoptosis.  Submitted.

Peichao Chen, Wei-Ke Ji, Fang-yuan Liu, Hong-Jiao Tang, Shujun Fu, Xinyan Zhang, Mugen Liu, Lili Gong, Mi Deng, Wen-Feng Hu, Xiao-Hui Hu, Xiao-Wen Chen,  Zi-li Li, Xi Li, Liu J-P, Li D W-C (2012). Alpha-Crystallin and Carcinogenesis.  Curr. Mol. Med. 12(9):1163-1173.

Wen-Feng Hu, Gong Lili, Zhi-Jun Cao, Haili Ma, Weike Ji, Mi Deng, Mugen Liu, Xiao-Hui Hu, Peichao Chen, Qin Yan, He-Ge Chen, Jiao Liu, Shuming Sun, Lan Zhang, Jinping Liu, Eric Wawrousek, and Li, D.W.-C. (2012). a-Crystallins interact with caspase-3 and Bax  to guard mouse lens development.  Curr. Mol. Med. 12(2): 177-187.

Mi Deng, Pei-Chao Chen, Sisi Xie, Jun-Qiong Zhao, Lili Gong, Jinping Liu, Lan Zhang, Shuming Sun, Jiao Liu, Haili Ma, Surinder Batra, and Li, D.W.-C. (2010). The Small Heal Shock Protein aA-Crystallin Is Expressed In Pancreas and Acts as A Negative Regulator of Carcinogenesis. Biochem. Biophys. Acta.-Molecular Basis of Diseases. 1802:621-631. PMID: 20434541.

Li, D. W-C., L Gong, M Deng, J-P Liu,M Liu, and Y-W Mao(2010). The two lens structural proteins, aA- and  aB-crystallins, prevent stress-induced apoptosis through regulation of multiple signaling transduction pathways. In: Arrigo, Simon (eds). Small Stress Proteins and Human Diseases. Nova Science Publisher, Inc NY, USA. Chapter 1.1:89-116. (review article).

Li H, C Li, Q. Lu, T Su, T Ke, D W-C Li, M Yuan, J Liu, X Ren, Z Zhang, S Zeng, Q K. Wang and M Liu (2008). Cataract mutation P20S of aB-crystalline impairs chaperone activity of aA-crystalline and induces apoptosis of human lens epithelial cells. Biophy. Biochem. Acta. 1782:303-309.

Li D W-C, Liu J-P, Mao YW, Xiang H, Wang J, Ma WY, Dong Z, Pike HM, Brown RE, Reed JC. (2005). Calcium-Activated RAF/MEK/ERK pathway mediates p53-dependent apoptosis and is abrogated by aB-crystallin through Inhibition of Ras Activation. Mol. Biol. Cell. 16:4437-4453.

Mao Y-W, Liu J, Xiang H, Li DW-C. (2004). Human aA and aB-Crystallins Bind to Bax and Bcl-XS to sequester their translocation during staurosporine- induced apoptosis. Cell Death and Differ. 11:512-526.

Liu JP, Schlosser R, Ma WY, Dong Z, Feng H, Liu L, Huang XQ, Liu Y, Li DW. (2004). Human aA- and aB-crystallins prevent UVA-induced apoptosis through regulation of PKCalpha, RAF/MEK/ERK and AKT signaling pathways. Exp Eye Res. 79(3):393-403. Erratum in: Exp Eye Res.79(6):807. Corrected and republished in: Exp Eye Res. 79(6):393-403. PMID: 15669141

Li DW-C, Xiang H, Mao YW, Wang J, Fass U, Zhang XY, Xu C. (2001). Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis. Exp Cell Res. 266(2):279-91.PMID: 11399056.

Mao YW, Xiang H, Wang J, Korsmeyer S, Reddan J, Li DW-C. (2001). Human bcl-2 gene attenuates the ability of rabbit lens epithelial cells against H2O2-induced apoptosis through down-regulation of the aB-crystallin gene. J Biol Chem. 276:43435-45.PMID: 11546795.

Currently, we are studying how a-crystallins regulate these different pathways and signaling targets to prevent lens cell apoptosis and cataractogenesis. 

Project 3. Role of Protein Serine/Threonine Phosphatases–2A in Carcinogenesis (Grant Support: W81XWH- 01-1-0474 from DOD, $750,000, 2008-2011,  PI: Ming-Fong Lin. Li DW-C, Co-Investigator; and Pending).

PP-2A is highly expressed in most cancer cells and modulate many different targets during carcinogenesis. Mutations of the scaffold subunits in PP-2A cause various types of cancer. Our recent work revealed that various transcription factors including Ets-1, CREB, AP-2a and SP-1 regulate PP2A-Aa. Moreover, we demonstrate that PP-2A is a target of the EGCG and PP-2A plays an important role in EGCG-mediated chemoprevention of carcinogenesis.  More recently, we have shown that PP-1 is also involved in regulation of carcinogenesis.

Our results on cancer research have been published in the following articles:

P-C Chen, C Li, D Wang, Z-W Luo, S-J Fu, X Li, Z-L Li, X-W Chen,

L Li, Z-X Huang, W-K Ji, X-H Hu, W-F Hu, M Deng, L Gong, JP Liu and D W-C Li. (2013). PP-1a and PP-1g Display Antagonism and Differential Roles in Tumorigenisity of Lung Cancer Cells.  Curr. Mol. Med. 13(1): 220-227.

P-C Chen, W-K Ji, F-Y Liu, H-J Tang, S-J Fu, X-Y Zhang, M Liu, L Gong, M Deng, W-F Hu, X-H Hu, X-W Chen,  Z-L Li, X Li, Liu J-P, Li D W-C (2012). Alpha-Crystallin and Carcinogenesis.  Curr. Mol. Med. 12(9):1164-1173.

C-H Liu, M Deng, J Xiang, H-L Ma, W Hu, Y Zhao, D. W.-C. Li**, and Song-Ping Liang** (2012). A novel spider peptide toxin suppresses tumorigenesis.  Curr Mol. Med. 12(10): 1350-1360

J Liu, WK Ji, SM Sun, L Zhang, H-G Chen, Y Mao, L Liu, X Zhang, L Gong, M Deng, L Chen, W-J Han, P-C Chen, W-F Hu, XH Hu, JP Liu, Z Woodward, W-B Liu,  Y-M Xiao, S-P Liang, Yun Liu S-J Liu and D W-C Li  (2012) The PP2A-Ab Gene Is Regulated by Multiple Transcriptional Factors Including Ets-1, SP1/SP3, and RXRa/b. Curr. Mol. Med.  12(8): 982-994.

Mi Deng, Pei-Chao Chen, Sisi Xie, Jun-Qiong Zhao, Lili Gong, Jinping Liu, Lan Zhang, Shuming Sun, Jiao Liu, Haili Ma, Surinder Batra, and Li, D.W.-C. (2010). The Small Heal Shock Protein aA-Crystallin Is Expressed In Pancreas and Acts as A Negative Regulator of Carcinogenesis. Biochem. Biophys. Acta.-Molecular Basis of Diseases. 1802:621-631. PMID: 20434541.

Chen H-G, W-J Han, M Deng, Qin J-C, J-P Liu, D Yuan, Liu J-P, Xiao L, Gong L, Liang S-P, Zhang J, Liu Y and Li D. W-C (2009). Transcriptional Regulation of PP2A-Aa is mediated by multiple factors including AP-2a, CREB, ETS, and SP-1. PLoS One. 4(9): e7019. PMID:19750005.

Qin J-C, He-Ge Chen, Qin Yan, Mi Deng, Liu J-P, S. Doerge, W-Y., Ma, Z. Dong, and Li, D. W-C. (2008). Protein phosphatase-2A is a target of epigallocatechin-3-gallate and modulates the p53-Bak apoptotic pathway. Cancer Res. 68(11):4150-4162. PMID: 18519674.

Currently, we are studying the key targets regulated by PP-2A and exploring how PP-2A regulates carcinogenesis through these targets.

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