Researchers@EVMS

The Galkina laboratory studies the involvement of the immune system in atherosclerosis, the disease that is the leading cause of heart attacks, stroke, and peripheral vascular disease. Our research is focused on understanding how atherosclerotic conditions affect immune cell functions, and how the immune system is involved in the regulation of the chronic inflammation within the artery wall and systemically in circulation and secondary lymphoid organs.

Mechanisms of B cell activation in atherosclerosis.

The B cell project is focused on processes that promote B cell subset –specific activation and functions in atherogenesis. While we know that atherosclerosis is characterized by vascular dysfunction, low-grade chronic inflammation, accumulation of modified lipoproteins, and recruitment of immune cells in the aorta, there is still much that is unknown about the mechanisms behind the disease progression. The uptake of modified low density lipoproteins (mLDL) by macrophages has been well characterized as being a major mechanism in the development of atherosclerosis. Recently, our laboratory showed that B cells can also uptake mLDL and this uptake induces some significant phenotypical changes in B cells. While mechanisms and role of mLDL uptake by macrophages are well-characterized, the pathways of mLDL uptake in B cells are unclear and nothing is yet known about the impact of mLDL uptake on B cell functions in atherosclerosis. In our current project, we investigate these important questions.

Myeloid cell-specific role of STAT4 in atherosclerosis and metabolic dysfunction

Our lab's studies on the implication of metabolic syndrome in the acceleration of atherosclerosis, led to the discovery of a key role for signal transducer and activator of transcription 4 (STAT4) as a central mediator of inflammation in the beta cell and in the aorta. We demonstrated that global deletion of STAT4 reduces islet dysfunction and atherosclerosis. Recently, we have discovered that STAT4 is expressed not only in Th1 cells, but also in neutrophils and IL-12 induces STAT4 phosphorylation. STAT4 role in myeloid cells has not been well-established and nothing is yet known about the role of STAT4 in neutrophils. Recently, we reported that STAT4 regulates macrophage phenotypes in atherosclerosis, but we still do not know how STAT4 and its downstream targets regulate macrophage functions. Our ongoing studies are investigating whether the IL-12/STAT4 axis serves as one of the key signals for macrophages and neutrophils to shape inflammatory functions of these cells, at least in part, by p66Shc-dependent mechanisms leading to atherosclerosis, beta cell functional decline and glucose intolerance.

Effects of fragmented sleep on atherogenesis

An exciting new area in the lab involves identifying specific mechanistic links between fragmented sleep and atherosclerosis. Sleep fragmentation is common in modern life and affects ~30% of the population. It increases in aging, occurs in conjunction with sleep apnea and has been linked to pathologies including hypertension, obesity, and type 2 diabetes, all of which are significant risk factors for atherosclerosis. To date, little is known about the direct effects of sleep fragmentation on atherosclerosis, associated islet dysfunction, and the immune response accompanying these pathologies. Our current investigations are focused on the role of sleep fragmentation in atherosclerotic plaque phenotypes, role of amygdala in the regulation of sleep fragmentation-driven immune response in atherosclerosis, and sex-dependent differences that drive atherogenesis in the conditions of sleep fragmentation and hyperlipidemia in females and males.