Dr. Mangala Rao received her Ph.D. in Biochemistry from The Indian Institute of Science, Bangalore, India. She completed her postdoctoral fellowship on IgE receptors on B lymphocytes in the laboratories of Dr. Arnold Froese, University of Manitoba, Canada, and Dr. Daniel H. Conrad, Johns Hopkins University School of Medicine, Baltimore, MD. She joined Dr. Carl R. Alving in 1990 as an NRC Senior Research Associate in the Department of Membrane Biochemistry, Division of Biochemistry at the Walter Reed Army Institute of Research and then became a research chemist in 1994. The department later merged with the US Military HIV Research Program.
The focus of the Rao laboratory has been to develop liposomes as carriers of antigens and vaccines, develop novel technologies for delivery of antigens and vaccines, including needle-free technology, elucidate the mechanisms involved in the processing and presentation of liposome-encapsulated antigens, and conduct preclinical testing of vaccines. These projects have utilized malaria, Ebola, dengue, anthrax and HIV antigens with a particular focus on HIV.
One of the major modes of HIV transmission is through the sexual route. Surprisingly there are major gaps in our understanding of the timing and the major events that occur upon HIV-1 entry at the early time points, the types of cells and receptors involved and the early immune responses generated. To address some of these questions, the Rao lab is utilizing a humanized DRAG mouse (NOD.Rag1KO.IL2RγcKO mice expressing HLA-DR0401molecules) generated by the Navy malaria group and in collaboration with them has shown that T follicular helper cells accumulate in the gut and female reproductive tract of these mice and are highly permissive to HIV. The abundance of human effector CD4 memory T cells and the high accumulation of TFH cells in the mucosal tissues of humanized DRAG mice makes this a suitable model to study HIV pathogenesis, the functional role of TFH cells, and to evaluate candidate vaccines. The Rao lab is actively pursuing the following research areas.
• Understanding the role of neutralizing antibodies in preventing the early entry of HIV into cells
• Elucidating the role of macrophages in HIV and characterizing the receptors on macrophages involved in HIV entry
• Understanding the role of 47 receptors in preventing HIV entry
• Understanding the role of T follicular helper cells in HIV infection
• Determining the immune responses generated in animals and in human clinical trials, in particular HIV V2-specific antibody responses during early infection and after vaccination with novel adjuvants and carrier systems
• Evaluating the efficacy of potential candidate HIV vaccines in humanized DRAG mice
Complete list of published work
1. Allam A, Majji S, Peachman K, Jagodzinski L, Kim J, Ratto-Kim S, Wijayalath W, Merbah M, Kim JH, Michael NL, Alving CR, Casares S, Rao M. (2015). TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1. Scientific Reports 5:10443. doi: 10.1038/srep10443.PMID:26034905.
2. Rao, M., Peachman, K.K., Kim, J., Gao, G., Alving, C.R., Michael, N.L., and Rao, V.B (2013). HIV-1 Variable Loop 2 and its Importance in HIV-1 Infection and Vaccine Development. Current HIV Research 5:427-438.2.
3. Alving, C.R., Peachman, K.K., Rao, M., Reed, S.G. (2012). Adjuvants for human vaccines. Curr Opin Immunol 24:310-315.
4. Karasavvas, N., Billings, E., Rao, M., Williams, C., Zolla-Pazner, S., Bailer, R.T., Koup, R.A., Madnote, S., Arworn, D., Shen, X., Tomaras, G.D., Currier, J.R., Jiang, M., Magaret, C., Andrews, C., Gottardo, R., Gilbert, P., Cardozo, T.J., Rerks-Ngarm, S., Nitayaphan, S., Pitisuttithum, P., Kaewkungwal, J., Paris, R., Greene, K., Gao, H., Gurunathan, S., Tartaglia, J., Sinangil, F., Korber, B.T., Montefiori, D.C., Mascola, J.R., Robb, M.L., Haynes, B.F., Ngauy, V., Michael, N.L., Kim, J.H., de Souza For The Moph Taveg Collaboration MS. (2012). AIDS Res Hum Retroviruses. 28:1444-1457.
5. Peachman, K.K., Wieczorek, L., Matyas, G.R., Polonis, V.R., Alving, C.R., Rao, M. (2010). The Importance of Antibody Isotype in HIV-1 Virus Capture Assay and in TZM-bl Neutralization. Viral Immunology 23:627-632.