Link between host microbiome, metabolites, inflammation and atherosclerosis
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 both with mature and bone marrow precursors. We think that this work will help to gain insight into the connection between cytokine signaling, dietary manipulated microbiome, inflammation and cardiovascular disease.
The role of cytokine signaling in and adipose tissue inflammation and its contribution to atherosclerosis and cancer
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.
Role of inflammation and cytokines in liver and colon cancers
We found that IL27R signaling plays an important role in the control of anti-tumor immunity in liver cancer and continues to dissect cellular and molecular mechanisms of its action. Because obesity is one of the most important pathogenic factors in HCC, we will elucidate the role of cytokine signaling in NASH and NAFLD as underlying inflammatory diseases preceding liver cancer in western populations. Using tissue- specific deleters and microbiome manipulations methods, we will address the role of cytokines signaling in the regulation of microbiota in obesity-driven liver cancer. We are planning to test the translational potential of IL27R inhibition in liver cancer along or in combination with other immunotherapies.
In collaboration with the Grivennikov Lab, we developed a model to test the role of IL27R signaling in colon cancer. The current work is focused on addressing the role of IL27R signaling to CRC progression and anti-tumor immunity.
Contact the Koltsova Lab
8700 Beverly Blvd
Davis Building Suite 2089
Los Angeles, CA 90004