Anna Aldovini, MD
|Hospital Title||Research Associate|
|Academic Title||Associate Professor of Pediatrics|
300 Longwood Avenue
Boston MA 02115
Anna Aldovini has a long-standing interest in the molecular biology of HIV and AIDS. The two goals of the laboratory are to improve understanding of HIV host-pathogen interactions and to develop new approaches to HIV/AIDS vaccines. Her studies in the area of HIV host-pathogen interactions are focused on how the virus affects host cell biology and progression to AIDS. The approaches to vaccine development that have emerged from her laboratory include the identification of non-infectious viral mutants and their use as DNA vaccines for mucosal immunization.
The long term goal in the area of HIV host-pathogen interactions is to understand the response to HIV-1 infection in the major target cells for this virus: dendritic cells, macrophages and T cells. Her laboratory explored the effects of HIV-1 and its Tat transactivator on primary antigen-presenting cells such as immature dendritic cells using DNA microarray analysis and functional assays and found that HIV-1 infection or Tat expression induces interferon-responsive genes in these cells without inducing maturation. Chemokines that recruit activated T-cells and macrophages, the ultimate target cells for the virus, were among the dendritic cell gene products induced by HIV-1 and Tat. Chemokine induction was shown to occurs also during retroviral infection in vivo. These results reveal a novel function for HIV-1 Tat, namely the reprogramming of host dendritic cell gene expression to facilitate expansion of the infection.
The goal of AIDS vaccine research is to establish an immunization regimen capable of stimulating both systemic and mucosal humoral and cell mediated immunity. Ongoing experiments are evaluating the effectiveness of mucosal DNA vaccination administered via different routes, how vaccine-induced immunity can be improved, and how an immunization regimen that involves different mucosal and systemic routes can provide high levels of systemic and mucosal responses within the same animal and contribute to protection from AIDS. The results of should be important not only for an AIDS vaccine development but also for the development of DNA vaccines for other mucosal pathogens.
About Dr. Aldovini
Dr. Aldovini obtained her M.D. from the University of Padua Medical School, Italy, where she also did her residency in Oncology. Subsequently she was a Fogarty Fellow at the N.I.H. in Bethesda, MD, and then a Research Scientist at the Whitehead Institute, Cambridge, MA.
- Izmailova , E., Bertley F., Huang, Q., Makori N., Miller C. J., Young R.A. and Anna Aldovini. HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T-cells and macrophages. Nature Medicine 2003 9:191-197.
- Wang S. W., Noonan, K. and Anna Aldovini. Nucleocapsid-RNA interactions are essential to structural stability but not to assembly of retroviruses. J. Virol., 78:716-723 (2004).
- Bertley F., Wang S.W., Kozlowski, P. A, Chappelle, J., A. Carville, K. Mansfield, D. Montefiori, J. D. Lifson, and A. Aldovini. Control of SHIV viremia and disease progression after nasal mucosa vaccination with a DNA-MVA Prime-Boost Vaccination Regimen. J. Immunology, 172: 3745 - 3757 (2004).
- Kim N, Dabrowska A, Jenner RG, and Aldovini A. Human and simian immunodeficiency virus-mediated upregulation of the apoptotic factor TRAIL occurs in antigen-presenting cells from AIDS-susceptible but not from AIDS-resistant species. Journal of Virology, J. Virology, 81:7584-97, (2007).
- Manrique M, Micewicz E., Kozlowski P, Wang SW, Aurora D, Wilson RL, Ghebremichael M, Mazzara G, Montefiori D, Carville A, Mansfield KG, and Aldovini A. DNA-MVA vaccine protection after X4 SHIV challenge in macaques correlates with day-of -challenge antiviral CD4+ T cell-mediated immunity levels and post-challenge preservation of CD4+ T cell memory. AIDS Research and Human Retroviruses, 24: 505-519, (2007).
- Dabrowska A., Kim N, and Aldovini A. Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T-lymphocytes. J. Immunology (in press). J. Immunology, 181:8460-8477, (2008).
- Mariana Manrique M., P. A. Kozlowski, S.-W. Wang, R. L. Wilson, E. Micewicz, D. Montefiori, K. G. Mansfield, A. Carville, and A. Aldovini. Nasal DNA-MVA SIV vaccination provides more significant protection from progression to AIDS than a similar intramuscular vaccination. Mucosal Immunology,2:439-449 (2009).
- Kim Nayoung, S. Kukkonen, S. Gupta and A. Aldovini. Association of Tat with the PP2A and PTEN promoters is the key event in transcriptional activation of apoptotic pathways in HIV-infected CD4+ T cells. PLoS Pathogens 6(9): e1001103. doi:10.1371/journal.ppat.1001103 (2010).
- Manrique M., P. A. Kozlowski, A. Cobo-Molinos, S.W. Wang, R.L. Wilson, D. C. Montefiori, K.G. Mansfield, A.Carville, and A. Aldovini. Long-term complete suppression of SIV viremia in half of infected female Rhesus macaques nasally vaccinated with DNA/rMVA. Journal of immunology, 2011;186;3581-3593.