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Zhaohui Feng , Ph.D. Feng

Assistant Professor

Division of Radiation Cancer Biology

Tel:    732-235-8814




  • M.D. Zhejiang University School of Medicine, Hangzhou, China
  • Ph.D. Zhejiang University School of Medicine, Hangzhou, China
  • Postdoc training: New York University School of Medicine

Cancer Institute of New Jersey/UMDNJ

Research Interests:

p53; tumor suppressor; stress response; apoptosis; energy metabolism; tumor; neurodegenerative diseases; aging.

As "the guardian of the genome”, the p53 tumor suppressor gene plays a critical role in maintaining genomic stability and tumor prevention. p53 is the most frequently-mutated gene in human tumors; over 50% of all tumors harbor mutations in the p53 gene, and over 80% of tumors have a dysfunctional p53 signaling pathway. The p53 protein responds to a wide variety of stress signals, including DNA damage (e.g. IR and UV), hypoxia, mitotic spindle damage, the inhibition of ribosome biogenesis, nutrition starvation and even the activation of oncogenes or the inactivation of tumor suppressor genes. These stress signals all interfere with the cellular homeostatic mechanisms that monitor and control the fidelity of DNA replication, chromosome segregation and cell division. As a transcription factor, once p53 is activated it selectively transcribes a set of target genes to initiate various cellular responses. Depending upon the cell type, and the type or degree of stress placed upon a cell, the p53 protein induces either cell cycle arrest, apoptosis or senescence to prevent the propagation of cells that could potentially become cancerous.

While cell cycle arrest, apoptosis and senescence are traditionally thought of as the major outputs of the p53 pathway, some recent studies are beginning to define additional functions of the p53 pathway. These functions include the regulation of DNA repair, IGF-1/mTOR pathways, energy metabolism, implantation of the embryo and aging. These findings suggest important functions of p53 in various cellular processes in addition to tumor suppression.

We are interested in the following research themes: 1) The role of p53 in regulating cellular energy metabolism and how this contributes to tumor suppression. Metabolic changes have been suggested to be a hallmark of tumor cells, and have been recently identified as possible contributors to malignant progression . Almost all t umor cells display altered energy metabolism, primarily utilizing glycolysis rather than the much more efficient aerobic respiration for their energy needs, a switch known as the Warburg effect. Recently, p53 has been shown to be directly involved in the regulation of mitochondrial respiration and p53 deficiency contributes to Warburg effect. We have identified some novel p53 target genes which may be directly involved in the regulation of cellular energy metabolism. We are studying how p53 regulates energy metabolism and tumor suppression through regulation of these genes. 2) p53 and aging. Like many other biological processes, aging is subject to regulation by genes that reside in pathways that have been conserved during evolution. The IGF-1/mTOR/p53 pathways are among those conserved pathways that impact upon longevity and aging-related diseases. Cancer is a disease of aging, and the accumulation of DNA mutations in critical genes (e.g. p53) in individual cells over a lifetime is thought to be the reason. Our recent finding demonstrates that p53 function declines with age especially in response to stress in mouse models, which may contribute to an enhanced mutation frequency and tumorigenesis in aged populations in addition to mutation accumulation. Furthermore, there is a great deal of communication between the p53 pathway and the IGF-1/mTOR pathways. These findings suggest the important role of p53 in regulation of aging and aging-related diseases. We are interested in studying mechanisms accounting for the decline of the p53 function in aging process and its effects on mutation, tumorigenesis and aging in both mouse models and human populations. 3) The role of p53 in regulation of physiological and pathophysiological functions of central nervous system, such as neurotransmission and neurodegenerative diseases.

Selected Peer-Reviewed Publications for the Recent 5 Years:

  1. Feng Z. , Hu W., Rajagopal G., Levine A.J. The Tumor Suppressor p53; Cancer and Aging. Cell Cycle . 2008; 7(7):842-847.
  2. Hu W., Feng Z. , Atwal G., Levine A.J. p53: a new player in reproduction. Cell Cycle. 2008; 7(7):848-852.
  3. Levine A.J., Hu W., Feng Z. Tumor suppressor genes. In: Mendelsohn et al (ed) The Molecular Basis of Cancer (third edition) , 2008, 31-39. Saunders, Elsevier, Philadelphia.
  4. Feng Z. , Hu W., Teresky A.K., Hernando E., Cordon-Cardo C., Levine A.J . Declining p53 function in aging: a possible mechanism for high tumor incidence in older populations . Proc Natl Acad Sci USA ., 2007; 104(42):16633-16638.
  5. Hu W., Feng Z (co-first author) , Teresky AK., Levine AJ. p53 regulates maternal reproduction through LIF. Nature ; 2007; 450 (7170): 721-724.
  6. Feng Z. , Hu W., de Stanchina E., Teresky A.K., Jin S., Lowe S., Levine A.J. The regulation of AMPK b 1, TSC 2 and PTEN expression by p53: Stress, cell and tissue specificity and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res., 2007; 67(7):3043-3053 .
  7. Hu W., Feng Z. , Ma L., Wagner J., Rice J.J., Stolovitzky G., Levine, A.J. A single nucleotide polymorphism in the Mdm2 gene disrupts the oscillation of p53 and Mdm2 levels in cells . Cancer Res., 2007; 67: 2757-2765 .
  8. Levine A.J., Hu W., Feng Z. , Gil G. Reconstructing Signal Transduction Pathways: Challenges and Opportunities. Ann N Y Acad Sci. 2007; 1115:32-50.
  9. Levine A.J., Hu W., Feng Z . The p53 pathway: what questions remain to be explored? Cell Death Differ. 2006; 13:1027-1036.
  10. Feng Z. , Jin S., Zupnick A., Hoh J., de Stanchina E., Lowe S.W, Prives C, Levine A.J. p53 Tumor Suppressor Protein Regulates the Levels of Huntingtin Gene Expression. Oncogene, 2006 ; 25:1-7.
  11. Levine A.J., Feng Z. , Mak T.W., You H., Jin S. Coordination and Communication between the p53 and IGF1-AKT-Tor signal transduction pathways. Genes & Development, 2006; 20:267-275.
  12. Feng Z. , Hu W., Yu H., Tang M.S. Acrolein is a major cigarette-related lung cancer agent: preferential binding at p53 mutational hotspots and inhibition of DNA repair. Proc Natl Acad Sci U S A, 2006;103:15404-15409.
  13. Feng Z. , Hu W., Marnett L.J., Tang M.S. Malondialdehyde, a major endogenous lipid peroxidation product, sensitizes human cells to UV- and BPDE-induced killing and mutagenesis through inhibition of nucleotide excision repair. Mutat. Res. 2006; 601:125-136.
  14. Feng Z. , Zhang H., Levine A.J., Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A, 2005;102:8204-8209.
  15. Harris, S.L., Gil, G., Hu, W., Robins, H., Bond, E., Hirshfield, K., Feng, Z., Yu, X., Teresky, A.K., Bond, G., Levine, A.J. Single-nucleotide polymorphisms in the p53 pathway. Cold Spring Harb Symp Quant Biol . 2005; 70 : 111-119.
  16. Feng Z. , Hu W., Tang M.S. Trans-4-hydroxy-2-nonenal inhibits nucleotide excision repair in human cells: a possible mechanism for lipid peroxidation-induced carcinogenesis. Proc Natl Acad Sci U S A, 2004 ; 101:8598-8602.
  17. Zhang X., Succi J., Feng Z. , Prithivirajsingh S., Story M.D., Legerski R.J. Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response. Mol Cell Biol., 2004; 24: 9207-9220.
  18. Hu W., Feng Z. , Tang M.S. Chromium(VI) enhances (+/-)-anti-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-induced cytotoxicity and mutagenicity in mammalian cells through its inhibitory effect on nucleotide excision repair. Biochemistry, 2004; 43:14282-14298.
  19. Hu W., Feng Z. , Tang M.S. Nickel (II) enhances benzo[a]pyrene diol epoxide-induced mutagenesis through inhibition of nucleotide excision repair in human cells: a possible mechanism for nickel (II)-induced carcinogenesis. Carcinogenesis, 2004; 25:455-462.
  20. Yoon J.H., Besaratinia A., Feng Z. , Tang M.S., Amin S., Luch A., Pfeifer G.P. DNA damage, repair, and mutation induction by (+)-Syn and (-)-anti-dibenzo[a,1]pyrene-11,12-diol-13,14-epoxides in mouse cells. Cancer Res. , 2004; 15:7321-7328.
  21. Feng Z. , Hu W., Chasin L.A., Tang M.S. Effects of genomic context and chromatin structure on transcription-coupled and global genomic repair in mammalian cells. Nucleic Acids Res, 2003; 31:5897-5906.
  22. Li J., Chen H., Ke Q., Feng Z. , Tang M.S., Liu B., Amin S., Costa M., Huang C. Differential effects of polycyclic aromatic hydrocarbons on transactivation of AP-1 and NF-kappaB in mouse epidermal cl41 cells. Mol. Carcinog., 2004; 40:104-115.
  23. Feng Z. , Hu W., Amin S., Tang M.S. Mutational spectrum and genotoxicity of the major lipid peroxidation product, trans-4-hydroxy-2-nonenal, induced DNA adducts in nucleotide excision repair-proficient and –deficient human cells. Biochemistry, 2003; 42 :7848-7854.
  24. Feng Z. , Hu W., Rom W., Costa M., Tang M.S. Chromium(VI) exposure enhances polycyclic aromatic hydrocarbon- DNA binding at the p53 gene in human lung cells. Carcinogenesis , 2003; 24:771-778.
  25. Hu W., Feng Z. , Tang M.S. Preferential carcinogen- DNA adduct formation at codons 12 and 14 in the human K-ras gene and their possible mechanisms. Biochemistry, 2003; 42:10012-10023.
  26. Hu W., Zhang Q., Su W.C., Feng Z. , Rom W., Chen L.C., Tang M.S., Huang X. Gene expression of primary human bronchial epithelial cells in response to coal dusts with different prevalence of coal workers' pneumoconiosis. J Toxicol Environ Health A, 2003; 66:1249-1265.