Blood and lymphatic vessels are critical to human health. Blood vessels supply every tissue in the body with blood and oxygen, while lymphatic vessels pick up rogue fluids that leak into tissues from the bloodstream and return them to the circulatory system for disposal.
When problems arise in these systems, the consequences can be dire and may cause diabetic retinopathy, a blindness-causing eye disease frequently seen in diabetic patients, or lymphedema, a painful swelling of the limbs. They can also contribute to cancer metastasis and atherosclerosis, among other serious conditions.
My lab is specifically interested in studying the endothelial cells that make up the lining of the blood and lymphatic vessels. We study cellular glucose metabolism, which governs how these cells use sugar and convert it into energy. This process can go wrong, with either too much or too little sugar converted, and in some cases, it can contribute to disease.
Using novel methods for studying these mechanisms, we hope to gain a better understanding of how to manipulate these cellular processes and develop new means of controlling the pathways that can lead to disease.
Lymphatic vessels maintain tissue fluid homeostasis. They also serve as essential conduits for tumor cell dissemination and the removal of cholesterol from the aortic wall. Accordingly, excessive or insufficient lymphangiogenesis (formation of the lymphatic vasculature) underlies the pathogenesis of multiple human diseases such as cancer, lymphedema, and atherosclerosis, for which curative treatments are not available. Thus, a better understanding of the mechanism of lymphangiogenesis may guide the development of new therapeutic strategies.
Our recent study has discovered that a novel cellular mechanism—endothelial glycolysis—plays a crucial role in lymphangiogenesis (Yu et al., Nature, 2017). Cells convert glucose into pyruvate through glycolytic metabolism, which generates ATP. Lymphatic endothelial cells exhibit robust glycolysis and heavily rely on this metabolic process for ATP production. Accordingly, glycolytic inhibition through genetic ablation of a rate-limiting glycolytic enzyme hexokinase 2 (HK2) profoundly impairs lymphatic vessel formation. Importantly, endothelial glycolysis can be enhanced by fibroblast growth factor (FGF)2 signaling via HK2 and is essential for FGF2-driven lymphangiogenesis. Our study highlights the importance of endothelial glycolysis in lymphatic vessel formation. It also indicates that lymphangiogenic signaling controls endothelial metabolism in order to elicit a metabolic state permissive for growth and proliferation.
Research projects of our laboratory are built upon this recent study to further study the crosstalk between metabolic programs and lymphangiogenic signaling events and to understand the involvement of cellular metabolism in the pathogenesis of vascular diseases.
B.S., Shandong University, China, 2005
Ph.D., Institute of Neuroscience, Chinese Academy of Sciences, China, 2010
Postdoctoral training, Yale University School of Medicine, 2012-2018
Honors and Awards
2019 American Heart Association Career Development Award
2018 Travel Award, International Vascular Biology Meeting, Helsinki
2015 American Heart Association Postdoctoral Fellowship
2010 ZhuLiYueHua Award for Outstanding Ph.D. Graduates, Chinese Academy of Sciences
Joined OMRF’s scientific staff in 2018
Song H, Zhu J, Li P, Han F, Fang L, Yu P. Metabolic flexibility maintains proliferation and migration of FGFR signaling-deficient lymphatic endothelial cells. J Biol Chem:101149, 2021 August, PMID: 34473994, PMCID: PMC8498002
Yu P, Wilhelm K, Dubrac A, Tung JK, Alves TC, Fang JS, Xie Y, Zhu J, Chen Z, Smet FD, Zhang J, Jin SW, Sun L, Sun H, Kibbey RG, Hirschi KK, Hay N, Carmeliet P, Chittenden TW, Eichmann A, Potente M, Simons M (2017). FGF-dependent metabolic control of vascular development. Nature, 545(7653):224-228. PMID: 28467822 PMCID: PMC5427179
Yu P, Alves TC, Kibbey RG, Simons M (2018). Metabolic Analysis of Lymphatic Endothelial Cells. Methods Mol Biol, 1846:325-334. PMID: 30242770
Tirziu D, Jaba IM, Yu P, Larrivée B, Coon BG, Cristofaro B, Zhuang ZW, Lanahan AA, Schwartz MA, Eichmann A, Simons M (2012). Endothelial nuclear factor-κB-dependent regulation of arteriogenesis and branching. Circulation, 126(22):2589-2600. PMID: 23091063 PMCID: PMC3514045
Yu P, Du JL (2011). Transient receptor potential canonical channels in angiogenesis and axon guidance. Cellular and Molecular Life Sciences, 68(23):3815-3821. (Co-corresponding authors) PMID: 21755360
Yu P, Gu SY, Bu JW, Du JL (2010). TRPC1 is essential for in vivo angiogenesis in zebrafish. Circulation Research, 106(7):1221-1232. (Highlighted in Faculty of 1000) PMID: 20185799
Huang C, Gu S, Yu P, Yu F, Feng C, Gao N, Du J (2010). Deficiency of smarcal1 causes cell cycle arrest and developmental abnormalities in zebrafish. Developmental Biology, 339(1):89-100. PMID: 20036229
Chen YM, Wang QJ, Hu HS, Yu P, Zhu J, Drewes G, Piwnica-Worms H, Luo ZG (2006). Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity. Proc. Natl. Acad. Sci. USA, 103(22):8534-8539. PMID: 16717194 PMCID: PMC1482526