Professor & Director Center for Genomics
Basic Sciences
Division of Microbiology
School of Medicine
Loma Linda University
Loma Linda, CA 92350
U.S.A
Phone:(909) 558-8759
Fax:(909) 558-4035
E-mail: chwang@llu.edu
Research Interest
Epigenomics and longevity/health
What determines lifespan in humans? Recent findings in animal models show that lifespan is not exclusively encoded in genes, and that epigenetic factors such as DNA methylation and histone modification of the genome have important roles. Longevity is therefore regulated by both genetic and environmental factors. To decipher the relationship between longevity and factors such as diet, life style, faith and other variables, a large and unique human study, the Adventist Health Study (AHS2), was initiated at LLU in Loma Linda, CA, one of the five blue zones in the world where many people enjoy a long and healthy life span. We will use state-of-the-art next-generation sequencing (NGS) technologies and cutting-edge genomic and bioinformatic tools to map out the epigenomic and transcriptomic fingerprints that are characteristic of longevity. Using systems biology approaches and through a 3-D study design, our objectives are: 1) decipher genome-wide DNA methylation and its relationship with aging/longevity; 2) determine long-term dietary (vegan) modulations and reprogramming of the epigenome and their relationship with aging; 3) define the molecular underpinning of health and disease by interrogating the epigenome and transcriptome of the AHS2 population. Our long-term goal is to gain a better understanding (from a systems biology perspective) of epigenomic reprogramming due to diet and life style in relation to longevity. This study is in collaboration with Dr. Penelope Duerksen-Hughes and Dr. Gary Fraser.
Other Collaborations (Wang NIH S10 Grant)
Dr. Lubo Zhang, PhD, Professor & Director of Center for Perinatal Biology, school of Medicine, LLU (Major User)
Gary Fraser, MD, PhD, Professor and Associate Dean of School of Public Health, LLU (Major User)
Hansel Fletcher, PhD, Professor & Vice Chair of the Department of Basic Sciences, Assistant Dean, School of Medicine, LLU (Major User)
Carlos Casiano, PhD, Professor & Associate Director, Center for Health Disparities and Molecular Medicine, School of Medicine, LLU (Major User)
Selected Publications
2015
1. Zhang, Y., Zhong, J., Qiu, H., MacLellan, W., Dr. Marban, E. and Wang, C. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells. Sci. Reports (NPG) 5, 17686; doi: 10.1038/srep17686 (2015).
2. Mitchell CJ, Getnet D, Kim MS, Manda SS, Kumar P, Huang TC, Pinto SM, Nirujogi RS, Iwasaki M,Shaw PG, Wu X, Zhong J, Chaerkady R, Marimuthu A, Muthusamy B, Sahasrabuddhe NA,Raju R, Bowman C, Danilova L, Cutler J, Kelkar DS, Drake CG, Prasad TS, Marchionni L, Murakami PN, Scott AF, Shi L, Thierry-Mieg J, Thierry- Mieg D, Irizarry R, Cope L, Ishihama Y, Wang C, Gowda H, Pandey A. A multi-omic analysis of human naïve CD+ T cells. BMC Syst Biol. 2015 Nov 6;9(1):75. doi: 10.1186/s12918-015-0225-4.
3. Boutrin MC, Yu Y, Wang C, Aruni W, Dou Y, et al. A putative TetR regulator is involved in nitric oxide stress resistance in Porphyromonas gingivalis. Mol. Oral Microbiol. 2015 doi: 10.1111/omi.12128.
4. Dou Y, Aruni W, Muthiah A, Roy F, Wang C, et al. Studies of the extracytoplasmic function sigma factor PG0162 in Porphyromonas gingivalis. Mol. Oral Microbiol. 2015 Jul 27. doi: 10.1111/omi.12122.
5. Zhang W, Yu Y, Hertwig F, Thierry-Mieg J, Zhang W, et al. Comparison of RNA-seq and microarray-based models for clinical endpoint prediction. Genome Biol. 2015 Jun 25;16:133. doi: 10.1186/s13059-015-0694-1.
2014
6.Wang Y, Han E, Xing Q, Yan J, Arrington A, et al. Baicalein upregulates DDIT4 expression which mediates mTOR inhibition and growth inhibition in cancer cells. Cancer Lett. 2015 Mar 28;358(2):170-9. doi: 10.1016/j.canlet.2014.12.033.
7. Dou, Y., Aruni, A., Luo, T., Roy, F., Wang, C. and Fletcher, H. Involvement of PG2212 a Zinc-finger protein in the regulation of oxidative stress resistance in Porphyromonas gingivalis W83. J. Bacteriol., 196 (23): 4057-4070, Sept. 2014
8. Gong B, Wang C, Su Z, Hong H, Sansone S-A, Rocca-Serra P, Auerbach S, Shi L, Tong W, Xu J. Transcriptomic profiling of rat liver samples in a comprehensive study design by RNA-seq. Sci. Data (NPG), 2014, 1:140021. DOI: 10.1038/sdata.2014.21.
9. Munro, S., Lund, S., Pine, P., Binder, H, Clevert, DA et al. Assessing Technical Performance in Differential Gene Expression Experiments with External Spike-in RNA Control Ratio Mixtures. Nature Commun., 2014 Sept.; 5:5125. doi: 10.1038/ncomms6125. PMID:25254650.
10. Li, S., Labai, P. P., Zubmo, P., Sykacek, P., Shi, W., Shi, L., Phan, J., Wu, PY, Wang, M., Wang, C. et al. Detecting and correcting systematic variation in large scale RNA sequencing data. Nature Biotechnol. Aug. 2014 (doi:10.1038/nbt.3000).
11. Su Z, Labaj PP, Li S, Thierry-Mieg J, Thierry-Mieg D, Shi W, Wang C. et. al. A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium. Nature Biotechnol. Aug. 2014 (doi:10.1038/nbt.2957).
12. Wang C, Gong B, Bushel, P. R., Thierry-Mieg J, Thierry-Mieg D. et al. Concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance. Nature Biotechnol. Aug. 2014 (doi:10.1038/nbt.3001).
13. Kelkar DS, Provost E, Chaerkady R, Muthusamy B, Manda SS… Wang, C and Pandey, A. Annotation of the zebrafish genome through an integrated transcriptomic and proteomic analysis. Mol. Cell Proteomics. 2014 Nov;13(11):3184-98. doi: 10.1074/mcp.M114.038299.
14. Wu, S., Li, X., Gunawaqrdana, M., Maquire, K., Guerrero-Given, D., Schaudinn, C., Wang, C., Baum, M., M. and Webster, P. Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism, PLoS ONE, July 09, 2014 DOI: 10.1371/journal.pone.0099204
15. Yu, Y., Zhao, C., Su, Z., Wang, C., Fuscoe, J., Tong, W., Shi, L. Comprehensive RNA-Seq transcriptomic profiling across 11 organs, 4 ages, and 2 sexes of Fischer 344 rats. Sci. Data (NPG), June 2014 (doi:10.1038/sdata.2014.13).
16. Yu, Y., Fuscoe, J. C., Chao, C., Guo, Chao, Jia, M., Qing, T., I Bannon, D. I Lancashire, L., Bao, W., et al. and Shi L. & Wang, C. A rat RNASeq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nature Commun., 5, 3230 2014 (doi:10.1038/ncomms4230).
2013
17. Zuo, C., Chen, X., Wang, Z., Wang, C., Xu, J., Wen, Z., Shi, L., Chow, M. S. S., Huang, Y. Utilization of Gene expression Signature for Quality Control of Traditional Chinese Medicine formula Si-Wu-Tang. AAPS, 2013, 15(3):884-92. doi: 10.1208/s12248-013-9491-5.
18. Warden, C., Lee, H., Tompkins, J. Li, X., Wang, C., Riggs, A., Yu, H., Jove, R., Yuan, YC. An integrative genomic pipeline for single-nucleotide resolution DNA methylation analysis. Nucleic Acid Res., 2013 April 17 PMID: 23598999.
19. Gunawardana M, Mullen M, Moss JA, Pyles RB, Nusbaum RJ, Patel, J, Vincent, KL, Wang, C et al. Global Expression of Molecular Transporters in the Human Vaginal Tract: Implications for HIV Chemoprophylaxis. PLoS ONE 8(10): 2013 e77340. doi:10.1371/journal.pone.0077340.
20. Nguyen GK, Hwang BH, Zhang Y, Monahan JFW, Davis GB, Lee, YS, Ragina, NP, Wang, C et al. Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps. PLoS ONE 8(8): 2013, e71628. doi:10.1371/journal.pone.0071628.
21. Chen G, Wang C, Shi L, et al. Comprehensively identifying and characterizing the missing gene sequences in human reference genome with integrated analytic approaches. Hum Genet., 2013, 132: 899-911.
22. IsHak, W. W., Elbau, I., Delaloye, S., Ha, K., Bolotaulo, N. I., Nashawati, R., Cassmassi, B., Wang, C. Quality of life in borderline personality disorder. Harvard Rev. Psychiat., 2013;21(3):138-150.
23. Liu, M., Fan, J., Wang, S., Wang, Z., Wang, C., Zuo, Z., Chow, S. S. C., Shi, L., Wen, Z., and Huang, Y. Transcriptional profiling of Chinese medicinal formula Si-Wu-Tang on breast cancer cells reveals phytoestrogenic activity. BMC Complement. Altern. Med., 13:11, 2013 (doi:10.1186/1472-6882-13-11).
24. Chen, G., Wang, C. Shi, L., Qu, X. Chen, J. Yang, J. Shi. C., Chen, L., Zhou, P. Y., Ning, B., Tong, W. and Shi, T. Incorporating the human gene annotations in different databases significantly improved transcriptomic and genetic analyses. RNA, 19(4): 479-489, 2013.
25. Niesen, C. E., Xu, J., Fan, S., Li, X., Wheeler, C. J., Mamelak, A., C., Wang, C. Transcriptomic profiling of human peritumoral neocortex tissue revealed genes possibly involved in tumor-induced epilepsy. PLoS ONE, 8(2): e56077, 2013.
2012
26. Li, W., Tian, E., Chen, Z., Sun, G. Q., Ye, P., Yang, S., Lu, D., Xie, J., Ho, T.V., Tsark, W. M., Wang, C., Horne, D. A., Riggs, A. D., Yi, M. L. R. and Shi, Y. Identification of Oct4- activating compounds that enhance reprogramming efficiency. PNAS, 109 (51): 20853- 20858, 2012.
27. Hines, H. M., Papa, R., Ruiz, M., Papanicolaou, A., Wang, C., Nijhout, F., McMillan, W. O., and Reed, R. D. Transcriptome analysis reveals novel patterning and pigmentation genes underlying Heliconius butterfly wing pattern variation. BMC Genomics, 13(288):1-16, 2012.
28. Tsui, S., Gao, J., Wang, C & Lu, L. CTCF mediates effect of insulin on glucagon expression. Exp. Cell Res., 318(8): 887-895, 2012.
29. Zheng, L., Dai, H., Zhou, M., Li, X. J., Liu, C., Guo, Z., Wu, X., Wu, J., Wang, C., Zhong, J., Huang, Q., Garcia-Aguila, J., Pfeifer, G. P., Shen, B. Polyploid cells rewire DNA damage response and repair networks to overcome DNA replication stress-induced senescence barriers for tumor progression. Nature Commun., 3(815), 2012.
30. Jin, W., Reddy, M. A., Chen, Z., Putta, S., Lanting, L., Kato, M., Park, J. T., Chandra, M., Wang, C., Tangirala, R., and Natarajan, R. Small RNA sequencing reveals microRNAs that modulate angiotensin II effects in vascular smooth muscle cells. J. Biological Chem.,2012
31. Boutrin, M. C., Wang, C., A. Wilson Aruni, A., Li, X., and Fletcher, H. M. Nitric oxide stress resistance in Porphyromonas gingivalis is mediated by pg0893 and other hypothetical genes of unknown function. J. Bacteriol. 2012, 194(6):1582.
Other Selected
32. Shi, L., Campbell, G., Jones, W. D., Campagne, F., Walker, S. J., Su, Z., Goodsaid, F. M., Pusztai, L., Shaughnessy, J. D., Oberthuer, A., …, Wang, C., Tong, W., Wolfinger, R. D. The MAQC-II Project: A comprehensive study of common practices for the development and validation of microarray-based predictive models. Nature Biotechnol., 2010, 28: 827-838.
33. Guo, L., Lobenhofer, E., K., Wang, C., Shippy, R., Harris, S. C., Zhang, L., Mei, N., Chen, T., Herman, D., Goodsaid, F. M., Hurban, P., Phillips, K. L., Xu, J., Deng, X., Sun, Y. A., Tong, T., Dragan Y. P., & Shi, L. Rat toxicogenomic study reveals analytical consistency across microarray platforms. Nature Biotechnol., 2006, 24: 1162-1169.
34. Shi, L., Reid, L., Jones, W…..Wang, C. Wilson, M. et al. The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements. Nature Biotechnol., 2006, 24: 1151-1161.