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Davide Zella, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Biochemistry and Molecular Biology

Additional Title:

Co-Head of the Laboratory of Tumor Cell Biology-Institute of Human Virology Member, Program in Tumor Immunology and Immunotherapy, Greenebaum Comprehensive Cancer Center

Location:

725 W. Lombard Street N458

Phone (Primary):

(410) 706-0995

Education and Training

1987: PhD: Biological Sciences, University of Pavia, Italy.

1989-1992: Post Doctoral fellow: National Research Council, Pavia, Italy.

1992-1995: Guest Researcher: Laboratory of Tumor Cell Biology, NCI, NIH, Bethesda, MD.

Biosketch

After completing his Ph.D. and post doctoral training, Dr. Davide Zella joined the Laboratory of Dr. R.C. Gallo at the National Institutes of Health in Bethesda, Maryland. Subsequently he followed Dr. RC. Gallo and joined the Institute of Human Virology and the School of Medicine at the University of Maryland, Baltimore. Dr. Davide Zella has more than 25 years of experience in the field of microbiology/virology, immunology, cancer biology and molecular biology. He has more than 50 publications, including peer reviewed articles and books chapters. Early in his career, Dr. Zella studied  the interactions between IFN-alpha and the immuno-system, in particular the anti-proliferative ability of IFN-alpha, the regulation of chemokine receptors by Interferons, and mechanisms of intracellular replication of HIV. Currently his Lab is studying the mechanism(s) of cellular transformation following interactions between components of the human microbiota and their host cells. We demonstrated that a strain of Mycoplasma promotes lymphomagenesis in an in vivo mouse model; and that a bacterial chaperone protein, DnaK, is implicated in the transformation process and resistance to anti-cancer drugs, by interfering with important pathways related to both DNA-damage control/repair and cell-cycle/apoptosis. Other tumor-associated bacteria carry a similar DnaK protein. Our data suggest a common mechanism whereby bacteria can be involved in cellular transformation and resistance to anti-cancer drugs by a hit and hide/run mechanism. Previous focus of Dr Zella's research has been done is collaboration with Professor Lu’s laboratory, leading to the characterization of the interactions between p53 and its antagonists (MDM2 and MDMX). In fact, inhibition of p53 through interaction with these antagonists is observed in about 50% of cancers, even though P53 is fully functional. Indeed, activation of p53 results in some cases in partial reduction of cancer cells number. Aim of the study was to design peptides able to block such interaction, thus reactivating p53.

Research/Clinical Keywords

Cancer biology, p53, microbiota, Mycoplasma.

Highlighted Publications

  1. Maciejewski J.P., Weichold F.F., Young N.S., Cara A., Zella D., Reitz M.S. and Gallo R.C. Intracellular expression of antibody fragments directed against HIV-1 reverse transcriptase prevents HIV-1 infection in vitro. Nature Medicine, 1:667, 1995
  2. Crowley R.W., Secchiero P., Zella D., Cara A., Gallo R.C. and Lusso P. Interference between human herpesvirus 7 and HIV-1 in monuclear phagocytes. J. Immunol., 156: 2004, 1996.
  3. Zella D., Barabitskaja O., Burns J. M., Romerio F., Revello M.G., Gerna G., Reitz M. S. Jr., Gallo R.C. and Weichold F.F. Interferon-gamma increases expression of chemokine receptors CCR1, CCR3 and CCR5, but not CXCR4 in monocytoid U937 cells. Blood, 91:4444, 1998.
  4. Zella D., Barabitskaja O., Casareto L., Romerio F., Secchiero P., Reitz M.S. Jr., Gallo R.C. and Weichold F.F. Recombinant IFN-alpha(2b) increases the expression of apoptosis receptor CD95 and chemokine receptors CCR1 and CCR3 in monocytoid cells. J. Immunol., 163: 3169, 1999.
  5. Zella D., Romerio F., Curreli S., Secchiero P., Zagury D. and Gallo R.C. IFN-alpha2b reduces IL-2 production and IL-2 receptor function in primary CD4+ T-cells. J. Immunol., 164: 2296, 2000
  6. *Secchiero P.,* Zella D., Curreli S., Mirandola P., Capitani S., Gallo R.C. and Zauli G. Pivotal role of cyclic nucleoside phosphodiesterase 4 in Tat-mediated CD4+ T cell hyperactivation and HIV type 1 replication. Proc. Natl. Acad. Sci., USA 97:14620, 2000.
  7. Romerio F, Zella D. MEK and ERK inhibitors enhance the anti-proliferative effect of interferon-alpha2b.  FASEB J.,  16:1680, 2002,
  8. Heredia A., Davis C., Amoroso A., Dominique J.K., Le N., Klingebiel E., Reardon E., Zella D. and Redfield RR. Induction of G1 cell cycle arrest in peripheral blood mononuclear cells results in increased extracellular levels of RANTES, MIP-1alpha and MIP-1beta: a strategy to inhibit replication of R5 strains of HIV-1. Proc. Natl. Acad. Sci. 100:4179, 2003.
  9.  Li C, Liu M, Monbo J, Zou G, Li C, Yuan W, Zella D, Lu WY, Lu W. Turning a scoprion toxin into an antitumor protein. J. Am. Chem. Soc., 130: 13546, 2008
  10. Pazgier M, Liu M, Zou G, Yuan W, Li C, Li C, Li J, Monbo J, Zella D, Tarasov SG, Lu W. Structural basis for the high-affinity peptide inibition of p53 interactions with MDM2 and MDMX. Proc. Natl. Acad. Sci., U S A.,  106:4665, 2009.
  11. Benedetti F, Davinelli S, Krishnan S, Gallo RC, Scapagnini G, Zella D, Curreli S. Sulfur compounds block MCP-1 production by Mycoplasma fermentans-infected machrophages through NF-KB inhibition.  J. Transl. Med., 12:145, 2014.
  12. Curreli S, Krishnan S, Reitz M, Lunardi-Iskandar Y, Lafferty MK, Garzino-Demo A, Zella D, Gallo RC, Bryant J. B cell lymphoma in HIV transgenic mice. Retrovirology., 10: 92, 2013.
  13. Benedetti F, Curreli S, Krishnan S, Davinelli S, Cocchi F, Scapagnini G, Gallo RC, Zella D. Anti-inflammatory effects of H2S during acute bacterial infection: a review. J Transl Med. 15: 100, 2017.
  14. Adebamowo SN, MA B, Zella D, Famooto A, Ravel J, Adebamowo C and the ACCME Research Group. Mycoplasma hominis and Mycoplasma genitalium in the vaginal microbiota and persistent high-risk human papilloma virus infection. Front. Public Health, 5:140, 2017.
  15. Zella D, Curreli S, Benedetti F, Krishnan S, Cocchi F, Latinovic OS, Denaro F, Romerio F, Djavani M, Charurat ME, Bryant JL, Tettelin H, Gallo RC. Mycoplasma promotes malignant transformation in vivo and its DnaK has broad oncogenic properties.  Proc. Natl. Acad. Sci., U S A., accepted for publication