Dr. Shiva Shahrara
Department of Medicine
Division of Rheumatology
email: [email protected]
Phone: (312) 413-7529
Research in the Division of Rheumatology at UIC focuses on uncovering the cellular & molecular mechanisms that are responsible for the inflammatory and bone erosive responses as well as immunometabolism regulation in rheumatoid arthritis (RA) & psoriatic arthritis (PsA) immune cells.
From Bench to Bedside:
The research program in our lab is focused on characterizing the function of effector macrophages & T cells in the early and later phases of RA and PsA.
Macrophages are a heterogeneous population of myeloid cells that polarize into different subtypes and can also mature into erosive osteoclasts. Macrophages are key producers of pro-inflammatory cytokines and precursors of osteoclasts; however, the pathways that control macrophage remodeling into inflammatory macrophages or erosive osteoclasts are not fully understood.
♦ We have identified unique inflammatory monokines that attract circulating monocytes into the joints and transform these cells into hypermetabolic macrophages in RA and PsA patients. We are specifically interested in delineating the hypermetabolic activity of RA and PsA inflammatory macrophages and how they communicate with effector T cells. Our goal is to identify novel checkpoints that can impair the hypermetabolic reprogramming of inflammatory macrophages & erosive osteoclasts and their interaction with T cells.
♦ We have found that the pro-angiogenic factors secreted from RA macrophages and fibroblasts control RA blood vessel formation and arthrogenicity. Hence our lab aims to uncover the importance of RA macrophages and fibroblast’s cross-regulation with vascular endothelium that is responsible for joint angiogenesis.
♦ Obesity impacts RA pathogenesis by influencing myeloid and lymphoid cell function in part through TLR activation. Our objective is to elucidate how a high-fat diet skews metabolic rewiring towards glycolytic hyperactivity and imbalanced oxidative phosphorylation and autophagy.
To answer these questions, we have excellent access to patient specimens and expertise in arthritic preclinical models.
• Regulation of metabolic RA macrophages and their crosstalk with effector T cells
• Interaction between RA fibroblasts and macrophages and their ability to trigger joint angiogenesis
• Mechanisms of bone destruction in RA & PsA
• Role of obesity in RA metabolic reprogramming