Research InterestsThe Rosenzweig Lab has a broad interest in the study of inflammatory disease. Although inflammation is essential for host defense against infection, its dysregulation contributes to a variety of inflammatory and/or autoimmune disorders. We are interested in how host defense mechanisms triggered by pathogenic microorganisms result in chronic inflammatory diseases such as uveitis (intra-ocular inflammatory disease) or arthritis. Specifically, we are interested in the mechanistic role of innate immune receptors such as the NOD-like receptors (NLRs) and the C-type lectin receptors (CLRs) in the orchestration of adaptive and autoimmune responses involved in disease. Understanding how NLRs such as NOD2 are a major cause of disease is important because NOD2 is the genetic cause of Blau syndrome (an inflammatory disease that manifests as uveitis, arthritis, and dermatitis). NOD2 is also a major genetic susceptibility factor in many other complex, inflammatory diseases including Crohn’s disease. Clinical issues of interest include uveitis, arthritis, autoimmune disease, autoinflammatory disease, and inflammation. Current studies focus on animal models of uveitis and arthritis that are driven by microbial triggers or an induced autoimmune response. Several approaches that include analysis of genetically modified mutant mice, molecular and cellular studies are used to elucidate the inflammatory mechanisms involved disease. The lab has a broach interest in the application of cutting edge technology to study disease-relevant issues including near-infrared (NIR) imaging of arthritis (Figure 1), live intravital videomicroscopy imaging of on-going cell trafficking responses in vivo (Figure 2), and topical endoscopy fundus imaging (TEFI) of the retina (Figure 3).
Figure 1. Near-infrared imaging is used to assess biomarkers of on-going spondylitis or peripheral arthritis in various murine models of disease. Shown here are representative images of NIR-scans of a mouse with more severe spondyloarthritis (left image) versus less severe disease (right image). The arrow indicates areas of microcalcification and bone remodeling (red signifies more intense signal, and blue signifies less intense signal). Image taken from Arthritis & Rheumatism (2012) vol. 64; issue 3, pp762-771.
Figure 3. Topical Endoscopic Fundus Imaging (TEFI). Fundus photographs of mice obtained by TEFI are captured by camera of anesthetized mice (A, B) and then qualitatively analyzed (C). Representative images depict a control (non-uveitic) mouse eye versus a diseased, uveitic mouse eye (E). High-resolution digital imaging of the fundus is a routine methodology we use to examine the onset and progression of disease.
The Rosenzweig lab is located at the Portland Veterans Affairs Medical Center, located on the top of Marquam Hill in Portland, Oregon (left image). The Portland VA has a long-standing and collaborative partnership with the School of Medicine at Oregon Health & Science University, and the 2 hospitals are physically connected to each other by a sky-bridge (right panel).
Rosenzweig lab staff in 2013. From left to right: Emily Vance, Brieanna Brown, Holly Rosenzweig, Ellen Lee, Rose Chuong.
Financial Support: National Eye Institute at National Institutes of Health; the Department of Veterans Affairs Laboratory Research and Development Service, and support from Research to Prevent Blindness Foundation.