Research in the De Maio Laboratory

Stress Response

The De Maio laboratory is interested in understanding the role of heat shock proteins in the response to inflammatory conditions. Although these proteins have a major function as molecular chaperones inside the cell, they have also been found outside cells released by an active mechanism different from cell-death. Extracellular heat shock proteins appear to act as signaling molecules modifying cellular physiology. The De Maio group discovered that Hsp70, the major inducible protein of the heat shock protein family, associated with membranes, forming ion conductance pathways (Arispe and De Maio 2000, Vega et al. 2008). Moreover, Hsp70 was found in the plasma membrane of stressed cells, and it was released to the extracellular environment associated with vesicles (Vega et al. 2008, De Maio 2011). Vesicle-associated Hsp70 induces a robust activation of macrophages (Vega et al. 2008).

The De Maio laboratory is currently investigating the mechanisms of Hsp70 insertion into membranes, its vesicle-associated release, and its interaction with target cells. These studies are very interesting, because Hsp70 contains neither a consensual secretory signal nor a hydrophobic domain that can predict membrane insertion.

Response to Injury

Trauma is the third leading cause of death in the United States and the first in individuals under 40 years of age. Frequency of mortality after trauma is complicated by the patient’s response to injury, which has been related to a stage of innate immune dysfunction (Cauvi et al. 2012, Bickler and De Maio 2013). The De Maio research group has demonstrated that the response to injury is modulated by several factors, including injury itself, environment, sex, age, and genetic make-up of the patient (De Maio et al. 2005).

The De Maio laboratory is investigating the molecular and genetic mechanisms that modulate the response and outcome from injury. In particular, we are studying the contribution of Scavenger Receptor A on the response of macrophages to inflammatory stimuli. In addition, we are investigating possible therapeutic approaches including the point of no-return from injury. In collaboration with Dr. Joseph Wang (Department of Nanoengineering), we are developing non-invasive biosensors to monitor the metabolic condition of the patient.


  1. N. Arispe and A. De Maio.  ATP and ADP modulate a Hsc70 cation channel in artificial acidic lipid membranes.  J. Biol. Chem. 275:30839-30843, 2000.
  2. S. W. Bickler and A. De Maio.  Dysfunction of the innate immune system during sepsis: a call for research. Crit. Care Med. 41: 364-365, 2013.
  3. 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.
  4. A. De Maio, A. Extracellular heat shock proteins, cellular export vesicles, and the Stress Observation System: a form of communication during injury, infection, and cell damage. It is never known how far a controversial finding will go! Dedicated to Ferruccio Ritossa. Cell Stress Chaperones 16: 235-249, 2011.
  5. A. De Maio, M. B. Torres, and R. H. Reeves. Genetic determinants influencing the response to injury, inflammation, and sepsis. Shock 23: 11-17, 2005.
  6. 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.