Research in the Immunopathogenesis Section is focused on understanding the molecular and immunological mechanisms of fibrosis induced by infection or chronic inflammation.
Tissue fibrosis or scarring is a leading cause of morbidity and mortality worldwide. Current health statistics suggest that nearly 45 percent of all natural deaths in the western world are attributable to some type of chronic fibroproliferative disease.
Fibrosis affects nearly all tissues and organ systems. Diseases in which fibrosis is a major cause of morbidity and mortality include the interstitial lung diseases, liver cirrhosis, kidney disease, heart disease, and systemic sclerosis, among others. Fibrotic tissue remodeling can also influence cancer metastasis and accelerate chronic graft rejection in transplant recipients.
Specific aims of the Immunopathogenesis Section include the following:
•Characterize the IL-13-dependent pathway of fibrosis and elucidate the function of novel downstream target genes that are regulated by Th2-associated cytokines, including Arginase-1, Relm-alpha, Muc5ac, and chitinase family proteins
•Understand the link between inflammatory mediators like IL-1, TNF-alpha, and IL-17 and pro-fibrotic cytokines like TGF-beta and IL-13 in various murine models of fibrosis
•Elucidate the role of alternatively activated macrophages (M2) and myeloid-derived suppressor cells in tissue remodeling, inflammation, and fibrosis
•Identify common and unique mechanisms of fibrosis in various organ systems and/or diseases, including persistent asthma, idiopathic pulmonary fibrosis, liver fibrosis, and systemic sclerosis
•Translate findings from mice to humans by establishing relevant preclinical models of fibrosis, so that novel therapies for schistosomiasis and other chronic fibroproliferative disorders might be evaluated quantitatively, in vivo, over time
The group uses transgenic and knockout mice to elucidate the mechanisms of fibrosis and Th2-dependent immunity in vivo.