Sealy Center for Molecular Medicine

Research Interests

The Macrophage Inflammatory Protein (MIP-1a) is a chemokine produced by viral infected lungs. MIP-1a has potent activities on natural killer (NK) cells and cytotoxic T lymphocytes (CTL) that may function as a bridge between innate and adaptive immune responses to RSV infection. In this project, we will be addressing four aims:

1. To identify the contribution of MIP-1a in the control of viral replication and development of RSV-induced lung inflammation, airway hyperresponsiveness and disease manifestations. In this aim, the role of MIP-1a will be investigated in MIP1-a deficient mice.
   
   
2. To investigate the requirement of MIP-1a for the migration and activation of NK cell and NK cell-driven CTL responses in RSV infection.
   
   
3. To analyze the spectrum of RSV-inducible proteins in the lung of mice, either control or MIP-1a deficient, using high throughput 2D SDS-PAGE and matrix-assisted laser desorption and ioinization time-of-flight (MALDI-TOF) mass spectroscopy. Here we will generate a database of proteins secreted in the bronchoalveolar lavage or lung tissue of RSV-infected mice. This powerful study will identify candidate proteins associated with virus-induced airway pathology controlled by MIP-1a.
   
   
4. To determine whether distinct protein patterns at the mucosal site can discriminate infants with different forms of illness or degree of chemokine responses following naturally-acquired RSV infections. The profile of proteins present in nasopharyngeal secretions collected from children with RSV infection will be analyzed by high resolution proteomics.

These studies will identify for the first time protein profiles associated with wheezing and severity of clinical illness in RSV infection.

Selected Publications

1. Haeberle, H., Nesti, F., Dieterich, H., Gatalica, Z., Garofalo, R.P. Perflubron reduces lung inflammation in respiratory syncytial virus infection by inhibiting chemokine expression and NF-kB activation. Am J Respir Crit Care Med 2002; 165:1433-1438
   
   
2. Jartti, T., van den Hoogen, B., Garofalo, R.P., Osterhaus, A. DME, Ruuskanen, O. New human metapneumovirus and acute wheezing in children. The Lancet 2002;360:1393-1394
   
   
3. Welliver, R.C., Garofalo, R.P., Ogra., P.L. Beta-chemokines, but neither T helper type 1 nor T helper type 2 cytokines, correlate with severity of illness during respiratory syncytial virus infection. Ped Infect Dis J 2002;21:457-461.
   
   
4. Haeberle, H., Takizawa, R., Casola, A., Brasier, A.R., Hans-Juergen D., van Rooijen, R., Gatalica, Z., Garofalo, R.P. Respiratory syncytial virus-induced activation of NF-kB in the lung involves alveolar macrophages and Toll-like receptor 4-dependent pathways. J Infect Dis. 2002;186:1199-1206
   
   
5. Haeberle, H., Casola, A., Gatalica, Z., Petronella S., Dieterich, H.-J., Ernst, P.B., Brasier, A.R., Garofalo, R.P. The IkB kinase is a critical regulator of chemokine expression and lung inflammation in respiratory syncytial virus infection. J Virol 2004;78:2232-41
   
   
6. Garofalo R.P., Hintz K.H., Hill V., Ogra P.L., Welliver R.C. Production of interferon gamma in respiratory syncytial virus infection of humans is not associated with interleukins 12 and 18. J Med. Virol 2004;73:289-294
   
   
7. Liu T, Castro S, Jamaluddin M, Brasier AR, Garofalo RP and Casola A. ROS mediate viral-induced Stat activation: role of tyrosine phosphatases. J Biol Chem 2004;279:2461-69
   
   
8. Brasier AR, Spratt H, Wu Z, Boldogh I, Zhang Y, Garofalo RP, Casola A, Pashmi J, Haag A, Luxon B and A Kurosky. Nuclear Heat Shock Response and Novel Nuclear Domain 10 Reorganization in Respiratory Syncytial Virus-Infected A549 Cells Identified By High Resolution 2D Gel Electrophoresis. J Virol 2004; 78:11461-11476.
   
   
9. Garofalo R.P., Hintz K.H., Hill V., Patti J., Ogra P.L., Welliver R.C. A comparison of epidemiologic and immunologic features of bronchiolitis caused by influenza virus and respiratory syncytial virus. J Med. Virol in press.