Narayanaswamy Ramesh conducts molecular studies on primary immunodeficiencies. Eventually his studies may lead to the development of a molecular framework for testing chemicals as potential therapeutic drugs. More immediate goals of his research are to:
- Identify the molecular basis of novel immune deficiencies that affect cytoskeletal functions.
- Delineate mechanisms that couple T-cell receptor signaling to the remodeling of the actin cytoskeleton.
- Understand the role of cytoskelton remodeling in T cell function(s).
His recent investigations have focused on Wiskott-Aldrich syndrome (WAS), which is caused by mutation in the gene encoding for the WAS protein (WASP). Ramesh and colleagues have been interested in the role of WASP on the cytoskeleton--the cell's dynamic structural framework -- which is composed of the protein actin and non muscle myosin. WASP has is known to have a role in cytoskeletal remodeling, which is essential to immune-cell functions, such as activation and motion.
Recently the Ramesh laboratory identified a novel cellular protein that acts as a negative regulator of WASP. The researchers have demonstrated that the protein, which they have named WIP, acts with WASP to regulate cytoskeletal remodeling during immune-cell activation. WIP is multifunctional, acting as a molecular scaffold and linking cellular signaling pathway(s) to actin in cytoskeletal remodeling. They are now studying the role of WASP and WIP in immune cell functions that require active cytoskeletal remodeling, such as chemotaxis, homing, and molecular events triggered by cell-cell and cell-matrix interaction.
- Martinez-Quiles NR, Rohatgi IM, Anton M, Medina SP, Saville H, Miki H, Yamaguchi T, Takenawa JH, Hartwig RS, Geha R, Ramesh N. WIP regulates N-WASP-mediated actin polymerization and filopodium formation. Nature Cell Biology 2001; 3: 484.
- Sasahara Y, Rachid R, Byrne MJ, de la Fuente MA, Abraham RT, Ramesh N, Geha RS. Mechanism of recruitment of WASP to the Immunological Synapse and of the activation following TCR ligation. Molecular Cell 2002; 10: 1269.
- Martinez-Quiles N, Ho,H.H., Kirschner,M.W., Ramesh,N. and Geha,R.S. Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP. Molecular and cellular Biology, 2004; 24, 5269. *Co-corresponding author.