Elena V. Tourkina, Ph.D.
Dr. Elena Tourkina is an Assistant Professor in the Division of Rheumatology & Immunology at the Medical University of South Carolina. She received an MS in Biochemistry and Virology at the Moscow State University and a Ph.D. in Molecular Biology at Belozerskiy Laboratory of Molecular Biology and Bioorganic Chemistry, Moscow State University, Moscow, Russia. She joined the Division of Rheumatology at MUSC in 1993.
Dr. Tourkina’s research interest is lung fibrosis and inflammation in scleroderma. Her scientific interests are the molecular and cellular mechanisms that regulate collagen synthesis and immune respond in healthy lungs and in pathological conditions such as fibrosis and inflammation. She recently established the role of caveolin-1, the main caveolae protein in the regulation of collagen expression and myofibroblast differentiation in the lung fibroblasts. It was demonstrated that caveolin-1 plays a central role in regulating collagen expression in normal lung fibroblasts (NLF) as a participant in a signaling cascade that also includes members of the PKC and MAPK families of signaling proteins. These studies also suggested that the low level of caveolin-1 expression in scleroderma lung fibroblasts (SLF) leads to their overexpression of collagen, and alpha-smooth muscle actin, the myofibroblast marker.
In the course of studies on caveolin-1 in lung fibrosis, it was found that several cell types in patient tissues and in animal models including lung fibroblasts, epithelial cells, monocytes, and neutrophils were deficient in caveolin-1 and that replacing caveolin-1 in these cells restored normal function in vitro and in vivo. It was intriguing that monocytes and fibroblasts were both deficient in caveolin-1 because a major portion of the fibroblasts present in fibrotic tissues are derived from bone marrow progenitors via the Bone Marrow Cell → Monocyte → Fibrocyte → Fibroblast lineage. Fibrocytes are transitional cells because they express both hematopoietic cell markers (CD45, CXCR4) and fibroblast markers (ColI). An attractive way to restore caveolin-1 function in vivo and in vitro is to use the caveolin-1 scaffolding domain (CSD) peptide. When this 20-amino acid domain of caveolin-1 is synthesized in fusion with the Antennapedia Internalization Sequence, it can enter cells, inhibit kinases, and thereby reverse the effects of caveolin-1 deficiency. CSD treatment inhibited fibrosis and monocyte and fibrocyte infiltration into damaged lung tissue in the mouse bleomcyin model for ILDs. and monocytes to fibrocytes differentiation in vitro. In addition, SSc patient monocytes, besides being deficient in caveolin-1, overexpress the chemokine receptor CXCR4 and are hypermigratory toward the CXCR4 ligand CXCL12. These pathological functions of SSc monocytes are reversed by CSD. There is a critical unmet need for treatments for the ILDs and other fibrotic diseases, and caveolin-1 is an outstanding molecular target for such treatments.
In additional studies, we found that African Americans (AA) may be prone to scleroderma due to the under expression of caveolin-1 in their monocytes. In other words, monocytes from healthy AA share pathological features with scleroderma monocytes including low caveolin-1 levels and high levels of differentiation and migration that can be reversed by CSD. The lack of caveolin-1 in AA may be related to the facts that TGFβ, the main profibrotic cytokine in scleroderma, is upregulated in healthy AA blood and that TGFβ inhibits caveolin-1 expression in various cell types. These observations suggest that AA are predisposed to scleroderma ILD due to the low caveolin-1 level in their monocytes and the resultant effects on signaling, migration, and fibrosis.
My main long-term goal is to develop a CSD-based treatment for ILD and other diseases involving a lack of caveolin-1. This is particularly important because there are currently no FDA-approved treatments for these diseases and they result in a very poor quality of life and ultimately death in affected patients. We are taking several pathways toward accomplishing this goal including: 1) Expanding our knowledge of the molecular mechanisms through which caveolin-1 regulates cell behavior, 2) Identifying additional diseases that involve a loss of caveolin-1 ann that therefore may also be responsive to CSD treatment. We already have a publication demonstrating that asthma may fall into this category. 3) Developing an improved version of CSD.
Both projects are supported by grants from the Scleroderma Foundation and from NIAMS.Dr. Tourkina's Curriculum Vitae (PDF Format)*
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