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Thomas Jefferson University - René Daniel, M.D., Ph.D.
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Qualifications
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M.D., 1st Medical School, Charles University, Prague, 1991
Ph.D., Molecular Biology and Genetics, Temple University, 1997
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Expertise and Research Interests
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My laboratory focuses on a key step of the HIV-1 life-cycle, called integration. During this step, HIV-1 DNA is joined to host cell DNA. We explore the role of host cell proteins in this process. We have shown that this step involves host cell DNA repair proteins involved in double-strand break DNA repair. These include proteins on the cellular non-homologous end joining pathway (NHEJ), ands ATM and ATR kinases. We demonstrated that these proteins are involved in the last, repair step of integration, also called post-integration repair. Our research results indicate that inhibition of these proteins results in a block in HIV-1 replication. Thus, the proteins may serve as targets for anti-HIV-1 therapy.
Our current experiments focus on the molecular analysis of the role of cellular proteins in targeting integration, and on development of new methods to target integration of retroviral gene therapy vectors to predetermined chromosomal regions.
The second area of research in my laboratory concerns differentiation of stem cells, including induced pluripotent stem (iPS) cells, which are made by reprogramming of somatic cells. Our objectives are: to determine how genetic diseases affect development and differentiation of stem cells (1); cellular co-factors that are specific for stem cells and control integration of retroviral vectors in this cell type (2).
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Publications
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- Recent selected Publications:
- Daniel, R., Katz, R.A. and Skalka, A.M. A role for DNA PK in retroviral integration. Science 284: 644-647, 1999.
- Daniel, R., Katz, R.A., Merkel, G., Hittle, J.C., Yen, T.J. and Skalka, A.M. Wortmannin potentiates integrase-mediated killing of lymphocytes and reduces the efficiency of stable transduction by retroviruses. Mol. Cell. Biol. 21: 1164-1172, 2001.
- Daniel, R., Litwin, S., Katz, R.A. and Skalka, A.M. Computational analysis of retrovirus-induced scid cell death, J. Virol. 75: 3121-3128, 2001.
- Daniel, R., Kao, G., Taganov, K., Favorova, O., Merkel, G., Yen, T.J., Katz, R.A., and Skalka, A.M. Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response, Proc. Natl. Acad. Sci. USA 100:4778-4783,2003.
- Daniel, R., Myers, C.B., Taganov, K., Greger, J.G., Merkel, G., Weber, I.T., Torshin, I., Harrison, R.W., and Skalka, A.M. Characterization of a novel inhibitor of retroviral integrases, AIDS Res Hum Retroviruses. 20:135-44, 2004.
- Daniel, R., Greger, J.G., Katz, R.A, Taganov, K.D., Wu, X., Kappes, J.C., and Skalka, A.M. Evidence that stable retroviral transduction and cell survival following DNA integration depend on components of the nonhomologous end joining repair pathway. J Virol. 78:8573-81, 2004
- Daniel, R., Ramcharan, J., Rogakou, E., Taganov, K.D., Greger J.G., Bonner, W., Nussenzweig, A., Katz, R.A., and Skalka, A.M. Histone H2AX is phosphorylated at sites of retroviral DNA integration but is dispensable for postintegration repair. J Biol Chem. 279:45810-4, 2004.
- Nunnari, G., Argyris, E., Fang, J., Mehlman, K., Pomerantz, R.J., and Daniel, R. Inhibition of HIV-1 Replication by the ATR and ATM Inhibitor Caffeine and Caffeine-Related Methylxanthines. Virology, 335: 177-184, 2005.
- Daniel, R. and Pomerantz, R.J. ATM: HIV-1s Achilles Heel? Nat. Cell Biol 7: 452-453, 2005.
- Smith, J.A., Wang, F.-X., Zhang, H., Wu, K.-J., Williams, K.J. and Daniel, R. Evidence that the Nijmegen breakage protein, an early sensor of double-strand DNA breaks (DSB), is involved in HIV-1 post-integration repair by recruiting the ataxia telangiectasia mutated kinase in a process similar to, but distinct from, cellular DSB repair. Virology J 5: 11-23, 2008.
- Daniel, R., and Smith, J.A. Integration site selection by retroviral vectors: molecular mechanism and clinical consequences. Hum Gene Ther 19: 558-67, 2008.
- Silvers, R., Smith, J.A., Schowalter, M., Litwin, S., Liang, Z., Geary, K, and Daniel, R. Modification of Integration Site Preferences of an HIV-1-based Vector by Expression of a Novel Synthetic Protein. Hum Gene Ther, in press, 2009.
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Individual Expertise profile of
René Daniel, M.D., Ph.D. , Copyright © René Daniel, M.D., Ph.D. .
Last Updated
by Admin
: Friday, November 13, 2009 1:04:16 PM
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