Research areas: Animal Biology/Physiology, Molecular Biology and Biochemistry
My laboratory investigates regulators of angiogenesis in skeletal muscle and adipose tissue, within the specific contexts of exercise, peripheral artery disease and obesity/diabetes. Angiogenesis is the growth of new capillaries and it is a critical adaptive mechanism that maintains healthy tissue functions. For example, in skeletal muscle in response to chronic exercise or during recovery from muscle damage, and in adipose tissue as it expands during obesity. During successful angiogenesis, endothelial cells within the capillary are activated, stimulated to proliferate then migrate away from the parent vessel into the surrounding extracellular matrix to join up eventually with another capillary. The regulation of this process is not well understood. My laboratory focuses on factors that repress angiogenesis, and how this can contribute to disease pathologies. We have found a pivotal role for a transcription factor known as Forkhead BoxO1 (FoxO1), which serves to suppress endothelial cell metabolism and proliferation. While this protein helps to maintain endothelial cells in a quiet state most of the time, if its levels increase too much, it will prevent endothelial cells from responding to an angiogenic stimulus. We have seen that this occurs in the ischemic muscle of individuals with peripheral artery disease, and in the endothelium of mice subjected to chronic high fat diet. These studies will help to uncover new therapeutic opportunities to improve the vascularization and function tissues in obesity and in peripheral artery disease.
Endothelial-specific FoxO1 depletion prevents obesity-related disorders by increasing vascular metabolism and growth. Rudnicki M, Abdifarkosh G, Nwadozi E, Ramos SV, Makki A, Sepa-Kishi DM, Ceddia RB, Perry CG, Roudier E, Haas TL.Elife. 2018 Dec 4;7. pii: e39780. doi: 10.7554/eLife.39780.
Female Mice Have Higher Angiogenesis in Perigonadal Adipose Tissue Than Males in Response to High-Fat Diet.Rudnicki M, Abdifarkosh G, Rezvan O, Nwadozi E, Roudier E, Haas TL. Front Physiol. 2018 Oct 23;9:1452. doi: 10.3389/fphys.2018.01452.
Leptin is a physiological regulator of skeletal muscle angiogenesis and is locally produced by PDGFRα and PDGFRβ expressing perivascular cells. Nwadozi E, Ng A, Strömberg A, Liu HY, Olsson K, Gustafsson T, Haas TL.Angiogenesis. 2018 Aug 18. doi: 10.1007/s10456-018-9641-6.
Endothelial FoxO proteins impair insulin sensitivity and restrain muscle angiogenesis in response to a high-fat diet. Nwadozi E, Roudier E, Rullman E, Tharmalingam S, Liu HY, Gustafsson T, Haas TL.FASEB J. 2016 Sep;30(9):3039-52. doi: 10.1096/fj.201600245R.
Endothelial FoxO1 is an intrinsic regulator of thrombospondin 1 expression that restrains angiogenesis in ischemic muscle. Roudier E, Milkiewicz M, Birot O, Slopack D, Montelius A, Gustafsson T, Paik JH, DePinho RA, Casale GP, Pipinos II, Haas TL.Angiogenesis. 2013 Oct;16(4):759-72. doi: 10.1007/s10456-013-9353-x