Shiva Shahrara
Email Address: shahrara@uic.eduCollege: Medicine Department: Medical Education
Secondary Department: Microbiology and Immunology
Title: Associate Professor
Office: 312 413 7529 Phone: 847 6603218
Participating in the Chancellor’s Undergraduate Research Awards program: Yes
Research Interest:
In the United States, 2.5 million people have rheumatoid arthritis (RA). RA is a chronic inflammatory autoimmune disorder that starts in the young to middle adult years and may lead to complete joint destruction. There is no cure for RA at present and a substantial percentage of patients do not respond to current therapy, therefore novel therapeutic approaches are urgently needed. To address this important issue, my laboratory focuses on identifying new targets and/or biomarkers for RA disease severity and response to effective therapy. To identify these novel targets or biomarkers for RA severity, we performed microarray studies in order to determine differentially regulated genes in macrophages obtained from synovial fluid of RA patients with active disease compared to normal macrophages and have found a number of important targets. We next examine the mechanism by which these factors mediate RA pathology initially utilizing RA peripheral blood, synovial tissue and synovial fluid and we subsequently determine whether blockade of this these factors could ameliorate the experimental arthritis model through the same underlying pathways identified in RA specimens.
A number of factors identified in our microarray analysis were shown to be important for monocyte extravasation. Monocyte migration plays a key role in the pathogenesis of RA since the number of monocyte derived macrophages is higher in RA compared to normal joints and is well correlated with radiological damage, joint pain and inflammation. Macrophages play a central role in RA pathogenesis by producing proinflammatory cytokines and chemokines, matrix metalloproteinases(MMPs), proangiogenic factors and differentiating to osteoclasts. Hence, factors modulating monocyte ingression can mediate inflammation and bone erosion. Therefore, one of the main objectives of our laboratory is to determine the molecular mechanism(s) responsible for enhanced recruitment of monocytes into the RA synovial joint space.
Another research interest in our laboratory is to inhibit angiogenesis in the early disease onset since angiogenesis is an early and a critical event in the pathogenesis of RA that promotes ingress of leukocytes and pannus formation thereby inhibition of neovascularization may block chronic inflammation.
A more recent interest that is being pursued is the identification of novel factors in RA synovial fluid and/or tissue that may be essential or are capable of synergizing with other known proinflammatory cytokines in inducing RA bone and cartilage erosion.
In short we hope that by taking a bench to bed side approach we will be successful in performing translational studies that would allow us to A. determine novel targets that inhibit neovascularization, monocyte recruitment and bone erosion in the RA joint and B. identify biomarkers that reflect RA disease severity and/or response to effective treatment. Minimum time commitment in hours per week: 15-20 Qualifications of a Student:
Prefer students that have prior research experience and are in the last year of their college. Honors college students with biology and pre-med backbround are preferred. Brief Summary of what is expected from the student:
Helping out with IRB and ACUC protocols. Culturing cells, treating cells and performing real-time RT-PCR. Also isolating mouse bone marrow cells and fibroblasts from human rheumatoid arthritistis synovial tissues. Differentiating human myeloid cells to osteoclasts. Homogenizing mouse ankles and performing ELISA.
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