Antonio De Maio
Professor of Surgery and Director of Center for Investigations of Health and Educational Disparities
Ph.D., Weizmann Institute of Science, Rehovot, Israel
Trauma is the number one cause of death in children and the third-leading overall killer of adults in the United States. The chances of mortality after trauma are complicated by the patientï¿½s own response to injury, which is demonstrated by exaggerated inflammatory response resulting in organ dysfunction and death. The inflammatory response after injury is modulated by several components, including the injury itself, the environment and the sex, age and genetic make-up of the patient. The main objective of our laboratory is to understand the inflammatory response after injury at the genetic and molecular levels. We are currently mapping genes that modulate the inflammatory process by using different mouse genetic resources. These genes can be used as genetic markers for identifying human patients that display a predisposition to inflammatory diseases. In addition, the molecular pathways in which these genes are involved can be investigated in isolated cell populations, such as macrophages. Another important component of the response to injury is the expression of genes encoding heat shock or stress proteins. The presence of these proteins confers protection to cells from subsequent stresses, a phenomenon called stress tolerance. Heat shock proteins have recently been found to regulate vesicle traffic in order to remodel the cell surface. Moreover, heat shock proteins released into the extracellular milieu following necrosis act as immunomodulators by interacting with lipid membrane components, particularly lipid rafts. The mechanism involved in this process is currently under investigation, and the information generated from these studies may be of help in the care of critically ill patients.
BMS Focus Areas:
D. Cauvi, D. Song, D. E. Vazquez, D. Hawisher, J. A. Bermudez, M.R. Williams, S. Bickler, R. Coimbra, and A. De Maio. A period of irreversible therapeutic intervention during sepsis correlates with a phase of innate immune dysfunction. J. Biol. Chem. 287: 19804-19815, 2012.
R. Drummond, D. Cauvi, D. Hawisher, D. Song, D. Nino, R. Coimbra, S. Brickler, and A. De Maio. Deletion of scavenger receptor A gene in mice resulted in protection from septic shock and modulation of Tlr4 signaling in isolated peritoneal macrophages. Innate Immunity PMID: 22751446, 2012.
Q. Zeidan, Z. Wang, A. De Maio and G.W. Hart. O-GlcNAc cycling enzymes associate with the translational machinery and modify core ribosomal proteins. Mol. Cell Biol. 21:1922-1936, 2010.
V. Vega, W. Charles, and A. De Maio. A new feature of the stress response: increase in endocytosis mediated by Hsp70. Cell Stress Chaperones 15: 517-527, 2010.
T. Frey and A. De Maio. The antifungal agent intraconazole induces the accumulation of high mannose glycoproteins in macrophages. J. Biol. Chem. 284:16882-16890, 2009.
V. Vega, W. Charles, and A. De Maio. A new feature of the stress response: increase in endocytosis mediated by Hsp70. Cell Stress Chaperones DOI: 10.1007/s12192-009-0165-2. Epub 2009.
V.L. Vega, M. Rodríguez-Silva,T. Frey, M. Gehrmann, J.C. Diaz, C. Steinem, G. Multhoff, N. Arispe and A. De Maio. Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. J. Immunol. 180:4299-4307, 2008.
J.M. Fuentes, W.B. Fulton, D. Nino, M.A. Talamini and A. De Maio. Atropine treatment modifies LPS-induced inflammatory response and increases survival. Inflamm. Res. 57: 111-117, 2008.
M. Gehrmann, G. Liebisch, G. Schmitz, R. Anderson, C. Steinem, A. De Maio, G. Pockley and G. Multhoff. Tumor-specific Hsp70 plasma membrane localization is enabled by the glycosphingolipid Gb3. PloS ONE 3:1925-1933, 2008.
T. Frey and A. De Maio. Increased expression of CD14 in macrophages alters inhibition of the cholesterol biosynthetic pathway by lovastatin. Mol. Med. 13: 592-604, 2007.
J.M. Fuentes, M.A. Talamini, W.B. Fulton, E.J. Hanly, A.R. Aurora and A. De Maio. General anesthesia delays the inflammatory response and increases survival from endotoxic shock. Clin. Vac. Immunol. 13:281-288, 2006.
K. Balakrishnan and A. De Maio. HSP70 binds its own mRNA as part of a gene expression self-limiting mechanism. Cell Stress and Chaperons 11:44-50, 2006.
W.B. Fulton, R.H. Reeves, M. Takeya and A. De Maio. A QTL Analysis to Map Genes Involved in LPS-Induced Inflammatory Response. Identification of Macrophage Scavenger Receptor 1 as a Candidate Gene. J. Immunol. 176:3767-3773, 2006.
M.B. Torres and A. De Maio. An exaggerated inflammatory response after CLP correlates with a negative outcome. J. Surg. Res., 125:88-93, 2005.
M.B. Torres, H. Trentzsch, D. Stewart, M.L. Mooney, J. Fuentes, D.F. Saad, R.H. Reeves and A. De Maio. Protection from lethal endotoxic shock after testosterone depletion is linked to chromosome X. Shock 24:318-323, 2005.
V.L. Vega and A. De Maio. Increase in phagocytosis after geldanamycin treatment or heat shock. Role of heat shock proteins. J. Immunol. 175:5280-5287, 2005.