Research Areas

We demonstrated the role of IL23 signaling in the regulation of microbiota and atherosclerosis (Fatkhullina et al., Immunity, 2018). Now we are interested in further investigating the role of cell type-specific cytokine signaling in the control of microbiota homeostasis and atherosclerosis development (using sophisticated tissue-specific mouse models now available in the lab). We will study how cytokines could affect microbiota-dependent metabolism and its effect on immune cells in both mature and bone marrow precursors. We believe that this work will help to gain insights into the connection between cytokine signaling, dietary manipulated microbiome, inflammation and cardiovascular disease.

We extend our research to the area of adipose tissue inflammation and its pathogenic role in both cardiovascular diseases and cancer. Perivascular fat is a fourth layer of any major blood vessel, including large arteria prone to atherosclerosis and AAA development. Obesity, adiposity and lipid-driven inflammation are also major and emerging risk factors for cancer progression, which could act locally (breast, liver) or systemically (many other types of cancer). We will enter this exciting field by elucidating the role of cytokine signaling in the regulation of adipocytes activation and determine the contribution of adipose tissue inflammation into the progression of atherosclerosis, abdominal aortic aneurysm and liver cancer.

We will continue our efforts to determine immune-mediated mechanisms driving abdominal aortic aneurysm development and progression. Immune mechanisms of AAA are investigated much less compared to atherosclerosis. The AAA field relies on the assumption that AAA and atherosclerosis have the same mechanisms of pathogenesis. Our work revealed an opposite role of IL27R cytokine in these two vascular pathologies, which provided us with a unique opportunity to address the question of how IL27R signaling actually participates in these diseases. We found that Angiotensin II (the enzyme that promotes vessel constriction and elevation of blood pressure) plays a critical role in the control of hematopoietic stem cell fate decision, where IL27R signaling plays an important role in how HSC would response to AngII, overall controlling AAA. Our current work is focused on the dissection of cellular and molecular mechanisms of how hematopoietic stem cells respond to cardiovascular relevant stress factors, what is the exact role of IL27R signaling in this response, and how systemic changes in diet and microbiome would affect HSC response to stress and AAA development.