Dr. Ray’s research is focused on two general areas: 1) Protective mechanisms in the lung that prevent acute lung injury specifically during bacterial pneumonia, and 2) Immunoregulatory mechanisms in the neonatal lung that defend against infections. To study these processes, he has developed mouse models of lung injury and infection using tissue-specific inducible transgenic or knockout mice.  Collectively, his findings on the one hand have significantly advanced our understanding of mechanisms that protect the lung from oxidative injury and on the other, have revealed immune mechanisms regulating lung inflammation in response to allergens, pathogens and immunomodulatory drugs.

In studies of bacterial pneumonia, Dr. Ray’s lab has identified pathways that induce the development of myeloid cells resembling myeloid-derived suppressor cells (MDSCs) in the lung that play an important role in immune regulation.  These studies have unraveled an interesting dynamic in the course of bacterial pneumonia that elicits the generation of IL-10-producing MDSCs during the late phase of inflammation. These MDSCs efficiently efferocytose apoptotic neutrophils thereby facilitating resolution of lung inflammation to restore pulmonary immune homeostasis. However, in non-resolving pneumonia, which causes significant morbidity and mortality, high levels of oxidized phospholipids generated during pneumonia impair IL-10 production from the MDSCs impairing resolution of inflammation. Ongoing studies are devoted to deciphering the underlying mechanisms.

Studies in Dr. Ray’s laboratory are also investigating host immune responses to infection by respiratory syncytial virus (RSV) in neonates using genetically altered mice as well as human primary lung and nasal epithelial cells co-cultured with immune cells. RSV infects every child by 2 years of age and in some infants can cause severe bronchiolitis requiring hospitalization. Multiple epidemiological studies have shown that severe disease induced by RSV is a risk factor for asthma development in later life. Work from his laboratory has for the first time identified an underlying mechanism which is impairment of regulatory T cell (Treg) function by RSV that breaches maternally-transferred immune tolerance (Nature Medicine 18:1525, 2012). His major current research focus in this area is on interactions between cells of the innate immune system and epithelial cells in early life that protect from RSV-induced pathology. These studies have the potential to identify targets for improving defense against RSV since effective vaccines against this virus are currently unavailable. Dr. Ray has trained multiple students, fellows and postdocs. His current research program involves active collaborations with scientists nationally as well as internationally.