|
||||
|
|
|
|||
 |
 |
||||||||||
Partida-Sanchez, Santiago
My laboratory is interested in the study of immune cell recruitment induced by infection and/or inflammation. We would like to understand the molecular mechanisms by which chemokine receptor signaling is controlled, and how directed cell migration (chemotaxis) is initiated. We have previously addressed the role for the ectoenzyme CD38 during neutrophil and dendritic cell (DC) trafficking to sites of inflammation and infection. CD38 is an enzyme capable of producing several calcium-mobilizing second messengers, cyclic adenosine diphosphate ribose (cADPR), adenosine diphosphate ribose (ADPR) and nicotinic acid adenosine diphosphate (NAADP) by catalyzing extracellular nicotinamide adenine dinucleotide (NAD+). CD38 is expressed on the surface of several hematopoietic cells, including: lymphocytes, monocytes, macrophages, neutrophils, and DCs. We have demonstrated that CD38-derived metabolites regulate chemokine receptor-stimulated calcium signaling, and are required for directional cell migration. Thus, CD38KO neutrophils are unable to migrate in vitro upon chemokine receptor stimulation induced by bacterial derived peptide (fMLF) or in vivo to the lung of S. pneumoniae infected mice (Partida-Sanchez S, et al. (2001). Nature Med 7(11): 209-1216). CD38 expression by DCs is also necessary for migration of immature DC precursors from the bone marrow to the skin and peripheral tissues and mature DCs from inflammatory sites to the draining lymph node (LN). Consequently, we have reported defective trafficking of CD38KO DCs resulting in inefficient T cell priming in the LN, poor expansion of antigen-specific T cells and significantly reduced humoral and cellular immune responses (Partida-Sanchez S, et al. (2004) Immunity 20:279-291). Our research projects are currently focused on molecular analyses of chemokine receptor-mediated G-protein-linked signaling and calcium influx in neutrophils and DCs. We are conducting experiments to study regulation of calcium influx mediated by CD38-catalyzed metabolites and the ADPR-activated calcium channel TRPM2 in inflammatory cells. We would like to assess whether CD38 inhibiting drugs, CD38-derived antagonists, and/or TRPM2 channel inhibitors, have potential therapeutic use to block undesired chronic inflammatory responses, or harmful T cell responses leading to autoimmunity. This knowledge could allow immunologists to predict new strategies for clinical intervention in several immunological disorders, as well as inflammatory and infectious diseases. Selected Publications Partida-Sanchez S, Rivero-Nava L, Shi G, Lund FE. CD38: an ecto-enzyme at the crossroads of innate and adaptive immune responses. Adv Exp Med Biol. 2007;590:171-83. PMID: 17191385
Partida-Sanchez Laboratory Personnel
Contact Columbus Children's Research Institute Links |
|||||||||||
 |
|||||||||||
 |
 |
||||||||||
Santiago Partida-Sanchez Ph.D. is an Assistant Professor of Pediatrics. He received his Ph.D. from the National Polytechnic Institute in Mexico City, and his postdoctoral training from The Trudeau Institute, Saranac Lake, NY. Dr. Partida-Sanchez joined the Center for Microbial pathogenesis at the Columbus Children’s Research Institute and Ohio State University in 2004. He is a faculty member of the Integrated Biosciences Graduate Program and the Graduate Program in Molecular, Cellular and Developmental Biology. Dr. Partida-Sanchez is interested in innate and adaptive immunity, focusing on molecular mechanisms of leukocyte motility, chemokine receptor signaling, generation of calcium second messengers, activation of calcium channels and their role in regulating migration of immune cells.