Daohong Zhou, M.D.

Professor
Pathology and Laboratory Medicine

Phone: (843) 792-7532
Fax: (843) 792-0368

Room 401
Walton Research Building

Education:

Research Interests:

  1. Elucidate the cellular and molecular mechanisms by which ionizing radiation (IR) and chemotherapy cause normal tissue damage and develop new interventions to ameliorate IR and chemotherapy-induced bone marrow suppression. Several novel antioxidants and cyto/radioprotectants have been developed in my laboratory and are currently undergoing extensive pre-clinical evaluation.
  2. Study the effects of genotoxic stress on hematopoietic stem cell (HSC) self-renewal and plasticity and examine if induction of senescence in HSCs contributes to cancer therapy-induced long-term bone marrow injury and premature ageing in an animal model.
  3. Understand the underlying mechanisms of tumor resistance to IR and chemotherapy by comparing the cellular responses (apoptosis, senescence or others) of normal adult tissue stem cells and those of tumor stem cells to IR and chemotherapy.

Current Funding: The studies outlined above are primarily supported by grants from the National Institutes of Health (NIH) and the Department of Defense (DOD):

Representative Recent Publications:

Zhou, D., Yu, T., Chen, G., Brown, S.A., Yu, Z., Mattson, M.P., Thompson, J.S. Effect of the gene-targeted disruption of the NF-kB1 (p50) gene on ionizing radiation-induced NF-kB activation and TNFa, IL-1a, IL-1b and IL-6 mRNA expression in vivo. Int. J. Radiat. Biol., 77:763-772, 2001.

Zhou, D., Lauderback, C.M., Yu, T., Brown, S.A., Butterfield, D.A., Thompson. J.S. D609 inhibits ionizing radiation-induced oxidative damage by acting as a potent antioxidant. J. Pharmacol. Exp. Ther., 298:103-109, 2001.

Chen, G., Yu, Z.. Zhou, D., Mattson, M.P.:  Phosphatidylinositol-3-Kinase - Akt and p42/p44 Mitogen-Activated Protein Kinases Mediate the Neurotrophic and Excitoprotective Actions of the Secreted Form of Amyloid Precursor Protein. Exp. Neurol. 175:407-14, 2002.

Lauderback, C.M., Drake, J.L., Zhou, D., Hackett, J.M., Castegna, A., Kanski, J., Tsoras, M., Varadarajan, S., and Butterfield, D.A.: Derivatives of xanthic acid are novel antioxidants: Application to synaptosomes. Free Radical Research, 37:355-365, 2003.

Meng, A., Wang, Y., Van Zant, G., Zhou, D. Ionizing Radiation and Busulfan Induce Premature Senescence in Murine Bone Marrow Hematopoietic Cells. Cancer Research, 63:5414-9, 2003.

Meng, A., Wang, Y., Brown, S.A., Van Zant, G., Zhou, D. Ionizing Radiation and Busulfan Inhibit Murine Bone Marrow Cell Hematopoietic Function via Apoptosis Dependent and Independent Mechanisms. Experimental Hematology, 31:1348-1356, 2003.

Meng, A., Yu, T., Chen, G., Brown, SA., Thompson, JS., Zhou,D.: Cellular Origin of IR-Induced NF-kB Activation in vivo and Role of NF-kB in Ionizing Radiation-Induced Lymphocyte Apoptosis. Int. J. Radiat. Biol., 79:849-861, 2003.

Brown SA, Konopa JL, Zhou D, Thompson JS. Expression of TNF-alpha by CD3 and F4/80 Positive Cells following Allogeneic Spleen Cell Transplantation. Bone Marrow Transplantation, 33(4):359-65, 2004.   

Meng A, Luberto C, Meier P, Bai A, Yang X, Hannun YA, Zhou D. Sphingomyelin synthase as a potential target for D609-induced apoptosis in U937 human monocytic leukemia cells. Experimental Cell Research, 292(2): 385-92, 2004.

Bai A, Meier GP, Wang Y, Luberto C, Hannun YA, Zhou D. Prodrug modification increases D609 chemical stability and cytotoxicity against U937 leukemia cells. Journal of Pharmacology and Experimental Therapeutics, 309: 1051-9, 2004.

Wang Y, Meng A, Zhou D. Role of Phosphatidylinositol-3-Kinase in Oxidative Stress-Induced Premature Senescence in Human Diploid Fibroblasts. Experimental Cell Research, 289:188-196, 2004.

Wang Y, Meng A, Lang H, Brown SA, Konopa JL, Kindy MS., Schmiedt RA, Thompson JA, Zhou, D. Lack of the NF-kB p50 or p65 gene sensitizes mice to ionizing radiation by increasing intestinal epithelial damage. Cancer Research, 63: 8791-812, 2004.

Grdina DJ, Murley JS, Kataoka Y, Zhou D, Seed TM. Radioprotectors: current status and new directions. Radiat Res. 163:704-5, 2005.

Wang Y, Schulte BA, Larue AC, Ogawa M, Zhou D. Total body irradiation selectively induces murine hematopoietic stem cell senescence. Blood, 107:358-66, 2006.

Wang Y, Schulte BA, Zhou D. Hematopoietic Stem Cell Senescence and Long-Term Bone Marrow Injury. Cell Cycle, 5:35-38, 2006.

Kawamori T, Osta W, Johnson KR, Pettus BJ, Tanaka T, Wargovich MJ, Reddy BS, Obeid LM, Hannun YA, Zhou D. Sphingosine kinase 1 is up-regulated in colon carcinogenesis. FASEB J, 20:386-8, 2006

Lang H, Schulte BA, Zhou D, Smythe N, Spicer SS, Schmiedt RA.  Deficiency of the p50 subunit of nuclear-factor kB causes progressive age-related auditory nerve degeneration and increased susceptibility to noise-induced hearing loss.  J Neuroscience, 26:3541-3550, 2006.

Lang, H., Ebihara Y, Schmiedt RA, Minamiguchi H, Zhou D, Smythe N, Liu L, Ogawa M, Schulte BA. Contribution of bone marrow hematopoietic stem cells to adult mouse inner ear: Mesenchymal cells and fibrocytes. Journal of Comparative Neurology, 496:187-201, 2006.

Wang Y, Probin V, Zhou D. Cancer therapy-induced residual bone marrow injury-Mechanisms of induction and implication for therapy. Current Cancer Therapy Review, 2: 271-279, 2006.

Probin V, Wang Y, Bai A, Zhou D. Busulfan selectively induces cellular senescence via a p53-independent but ERK-p38 MAPK-dependent mechanism. J. Pharmacol. Exp. Ther.  319:551-60, 2006.

Probin V, Wang Y, Zhou D. Busulfan-induced senescence is dependent upon ROS production upstream of the MAPK pathway. Free Radical Biology and Medicine, in revision, 2006.

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