Edward Janoff
Professor M.D., University of Arizona School of Medicine
Current Research
We focus on diseases of international importance, such as diarrheal disease, respiratory infections, and HIV-1/AIDS. Our team characterizes mucosal responses to Streptococcus pneumoniae in the lung and to HIV-1 in the intestine, reproductive tract, and in breast milk. Each study is supported by a field site in Africa (Uganda, Burkina Faso, Botswana and South Africa) with collaborators from these African nations, the U.S. and Europe. The goal of our laboratory is to provide a scientific foundation for mucosal vaccines to prevent pneumococcal infections and transmission of HIV-l /AIDS. We integrate clinical and basic laboratory approaches to determine how pathogens interact with the host at the mucosal surface and how innate and humoral mechanisms, individually and in concert, serve to protect against infection. Our primary model for mucosal defense against HIV involves post-natal transmission of the virus by breast milk. We are characterizing the mechanisms by which pathogen-specific antibodies in blood and milk from transmitting and non-transmitting mothers in Burkina Faso, Botswana and Uganda, neutralize autologous and heterologous HIV isolates using cellular, molecular, and biochemical approaches. For S. pneumoniae, we characterize systemic and mucosal responses to natural infection and vaccine, the molecular basis for capsule-specific antibody responses (VH gene diversity and mutational pattern), and the functional activity of these human antibodies. The goal is to develop effective vaccines against these pathogens to prevent infections where they begin, at the mucosa.
Recent Publications
Shapiro RL, Lockman S, Kim S, Smeaton L, Rahkola JT, Thior I, Wester C, Moffat C, Arimi P, Ndase P, Asmelash A, Stevens L, Montano M, Makhema J, Essex M, Janoff EN. Infant morbidity, mortality, and breast milk immunologic profiles among breastfeeding HIV-infected and HIV-uninfected women in Botswana. J Infect Dis 2007; In press.
Fasching CE, Grossman T, Corthesy B, Plaut AG, Weiser JN, Janoff EN. Impact of the molecular form of IgA on functional activity in defense against Streptococcus pneumoniae. Infect Immun. 2007;75: 1801-10.
Feikin DR, Feldman C, Schuchat A, Janoff EN. Global strategies to prevent bacterial pneumonia in adults with HIV disease: an evidence-based review. Lancet Infect Dis 2004;4:445-455.
Weiser JN, Bae, D, Fasching C, Scamurra RW, Ratner AJ, Janoff EN. Antibody-enhanced pneumococcal adherence requires IgA1 protease. Proc Natl Acad Sci USA 2003:100:4215-4220.
Scamurra RW, Nelson DB, Lin XM, Miller DJ, Silverman GJ, Kappel T, Thurn JR, Lorenz E, Kulkarni-Naria A, Janoff EN. Mucosal plasma cell repertoire during HIV-1 infection. J Immunol 2002;169:4008-4016.
Finn A, Zhang Q, Seymour L, Fasching C, Pettitt E, Janoff EN. Induction of functional secretory IgA responses in breast milk by pneumococcal capsular polysaccharides. J Infect Dis 2002;186:1422-1429.
Tasker SA, Wallace MR, Rubins JB, Paxton WB, O'Brien J, Janoff EN. Reimmunization with 23-valent pneumococcal vaccine in HIV-1-infected patients: clinical, immunologic, and virologic response. Clin Infect Dis 2002;34:813-821.
Pillay K, Coutsoudis A, Agadzi-Naqvi AK, Kuhn L, Coovadia HM, Janoff EN. Secretory leukocyte protease inhibitor (SLPI) in vaginal secretions and perinatal HIV-1 transmission. J Infect Dis 2000;183:653-56.
