top of page

Research Program

Our primary research focus is broadly on the interface between sterile and infectious inflammation and how the innate immune system is able to distinguish between the two and respond appropriately.  Given my clinical interest in trauma anesthesia, and specifically the airway, respiratory and hemodynamic management of critically-ill trauma patients, the lab's research focuses on lung injury in trauma and the pathophysiology of lung ischemia reperfusion (IR) injury.  We are interested in how damage markers are generated in IR injury, how these are sensed and how infiltrating immune inflammatory cells are targeted to the lung.  Dissecting the individual aspects of these processes will provide important insights towards improving the way trauma and other patients with IR injury are clinically cared for.

 

Furthermore, by understanding the molecular and cellular basis of lung IR injury, we hope to gain insights into how this process interfaces with coexisting or superimposed infections that are encountered by sick trauma patients in the ICU.  These pathogenic, commonly bacterial, nosocomial infections often target the lung with devastating consequences given the relative immune paralysis that often accompanies severe trauma.

 

We utilize a mouse model of lung ischemia reperfusion injury to investigate the details of this maladaptive process. By using fluorescent and bioluminescent markers to track the presence and activation status of inflammatory cells in live animals, we can determine the kinetics of the initiation, progression, and resolution phases of the lung IR-generated inflammation, as well as the effects of therapeutic interventions. We also aim to use fluorescently tagged bacteria as well to track active infections and identify the primary infected/sensor cell type(s). Understanding the interactions between lung IR injury and concurrent lung infection would allow us to design treatment and prevention strategies for severely ill hospitalized trauma patients. 

Mouse Model of Lung Ischemia Reperfusion (IR)

Neutrophils trafficking to the lung after ischemia reperfusion injury are not activated and as shown above are localized to the lung interstitium (red fluorescent signal = RFP+ neutrophils) and not in the alveoli (a) or vasculature (v)

What is key about our model of lung ischemia reperfusion (ventilated lung IR) is that oxygenation and gas exchange continues throughout the process with minimal periods of mechanical ventilation. Other factors that make this model superior to other existing models of lung IR are shown to the right.

 

This unilateral ventilated lung ischemia reperfusion mouse model was developed and refined by Jeffrey Dodd-o from Johns Hopkins Medicine: Department of Anesthesia and Critical Care Medicine.

bottom of page