Research in the De Maio Laboratory

Trauma is the third leading cause of death in the United States.  Frequency of mortality after trauma is complicated by the patient’s response to injury.  For example, the initial insult could trigger a situation of exaggerated inflammatory response that results in organ dysfunction and death. The response to injury is modulated by several components, including the injury itself, the environment, sex, age, and genetic make-up of the patient (see Figure).  The objective of our laboratory is to understand the response to injury at the genetic and molecular levels.  The genetic component of the response to injury (inflammation) is studied using inbred mouse strains (see Figure). 

Genes involved in this response are mapped using mouse genetic resources (see Figure).  These genes can be used as genetic markers to identify a particular susceptibility to disease in humans. In addition, the molecular pathways in which these genes are involved can be investigated in isolated cell populations, such as macrophages (see Figure) and hepatocytes.  An important component of the response to injury is the expression of genes encoding heat shock or stress proteins (see Figure).  The presence of these proteins confers protection to cells from subsequent stresses, a phenomenon coined stress tolerance.  We are investigating the molecular mechanism involved in stress tolerance. In addition, the expression of heat shock or stress proteins is regulated by a self-limiting mechanism that reduces the expression of these genes.  This self-limiting mechanism includes changes in the stability of Hsp70 mRNA, which are mediated by binding of Hsp70 to its own message. We are also investigating the role of heat shock proteins in vesicle trafficking. Moreover, heat shock proteins released into the extracellular milieu following necrosis act as immunomodulators by interacting with lipid membrane components. The mechanism involved in this process is currently under investigation (see Figure). The information generated from these studies may be of help in the care of critically ill patients.