The research interests of Dr. Huo's laboratory are to study metabolic aspects of human diseases in animal models.
These studies include examination of metabolic effect on leukocyte recruitment and activation, fibroblast activation, activation and proliferation of vascular cells in animal models of atherosclerosis, thrombosis, diabetes/obesity, pulmonary hypertension, retinopathy, cardiac hypertrophy and renal fibrosis. The above diseases develop and progress because of metabolic modulation in relevant cells. Dr. Huo's laboratory developed in-vitro, ex-vivo, and in-vivo animal models and various engineered mice. Using these animal disease models, epifluoresence intravital microscopy, FCAS and histological approaches as well as various molecular/genetic assays, the phenotypes of disease models are characterized and the underlying molecular mechanisms are studied. Current studies assess the involvement of AMPK, adenosine/adenosine receptors, PFKFB3, ATIC and sirtuins in the development and progression of above diseases. These studies are expected to augment basic understanding of metabolic aspect involved in these diseases, and may lead to the development of metabolic therapy for future clinical use in patients.
Targeting myeloid glycolysis in pathological ocular angiogenesis
The aims of this project are to investigate the role of PFKFB3 in myeloid cells in retinal endothelial proliferation, migration as well as sprouting.
PFKFB3 in pulmonary vascular remodeling
The proposed research will study the role of PFKFB3 in vascular remodeling in the process of pulmonary hypertension development in mice.
The role of adenosine kinase in the formation of aortic aneurysm
The aims of this project are to investigate the role of ADK in leukocytes and vascular cells in the formation of abdominal aortic aneurysm.
ADK regulation of fat metabolism and insulin sensitivity
The propose of this project will study how excessive ADK drives dysregulation of hepatocyte-macrophage crosstalk to promote hepatic fat deposition and inflammation, as well as hepatic and systemic insulin resistance via mechanisms involving impaired adenosine-adenosine 2A receptor signaling and/or increased DNA methylation.
Mechanisms of myeloperoxidase and Nox4 interactions in abdominal aortic aneurysm
The purpose of this project is to determine how myeloperoxidase gets into the aortic wall to cause aneurysms and explore whether medications that block white blood cells from releasing myeloperoxidase can be used to treat aortic aneurysms.
New Treatment targets found for blinding retinal disease
New pulmonary hypertension treatment target in the bull’s-eye
New treatment target identified for diabetic complications
Liu Z, Xu J, Ma Q, Zhang X, Yang Q, Wang L, Cao Y, Xu Z, Tawfik A, Sun Y, Weintraub NL, Fulton DJ, Hong M, Dong Z, Smith LEH, Caldwell RB, Sodhi A, Huo Y. Glycolysis links reciprocal activation of myeloid cells and endothelial cells in the retinal angiogenic niche. Sci Transl Med. 2020 Aug 5;12(555):eaay1371. doi: 10.1126/scitranslmed.aay1371. PMID: 32759274.
Wang Y, Xu Y, Yan S, Cao K, Zeng X, Zhou Y, Liu Z, Yang Q, Pan Y, Wang X, Boison D, Su Y, Jiang X, Patel VS, Fulton D, Weintraub NL, Huo Y. Adenosine kinase is critical for neointima formation after vascular injury by inducing aberrant DNA hypermethylation. Cardiovasc Res. 2020 Feb 17:cvaa040. doi: 10.1093/cvr/cvaa040. Epub ahead of print. PMID: 32065618.
Cao Y, Zhang X, Wang L, Yang Q, Ma Q, Xu J, Wang J, Kovacs L, Ayon RJ, Liu Z, Zhang M, Zhou Y, Zeng X, Xu Y, Wang Y, Fulton DJ, Weintraub NL, Lucas R, Dong Z, Yuan JX, Sullivan JC, Meadows L, Barman SA, Wu C, Quan J, Hong M, Su Y, Huo Y. PFKFB3-mediated endothelial glycolysis promotes pulmonary hypertension. Proc Natl Acad Sci U S A. 2019 Jul 2; 116(27):13394-13403. PMID: 31213542; PMCID: PMC6613097.
Zhou Y, Zeng X, Li G, Yang Q, Xu J, Zhang M, Mao X, Cao Y, Wang L, Xu Y, Wang Y, Zhang Y, Xu Z, Wu C, Chen JF, Hoda MN, Liu Z, Hong M, Huo Y. Inactivation of endothelial adenosine A(2A) receptors protects mice from cerebral ischaemia-induced brain injury. Br J Pharmacol. 2019 Jul; 176(13):2250-2263. PMID: 30931525; PMCID: PMC6555863.
Kovacs L, Cao Y, Han W, Meadows L, Kovacs-Kasa A, Kondrikov D, Verin AD, Barman SA, Dong Z, Huo Y*, Su Y*. PFKFB3 in Smooth Muscle Promotes Vascular Remodeling in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med. 2019 Feb 28. doi: 10.1164/rccm.201812-2290OC. PMID: 30817168. *Co-corresponding.
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