Longhou Fang

Longhou Fang, PhD

Associate Professor of Cardiovascular Sciences, Academic Institute
Associate Member, Research Institute
Houston Methodist
Weill Cornell Medical College


Description of Research

The Fang laboratory is focused on exploring the role of lipid metabolism in vascular function, including angiogenesis, lymphangiogenesis, and hematopoiesis, using both zebrafish and mouse models. 
One significant part of the laboratory research stems from Dr. Fang’s prior discovery that Apolipoprotein (APOA1) binding protein (AIBP) controls angiogenesis via regulation of caveolae/lipid rafts and the associated VEGFR2 signaling (Nature2013;Circ Res2017;Commun Biol2020). Our ongoing research will further define the detailed signaling machinery in distinct vascular beds. In addition, we are also interested in how lipid metabolism controls hematopoiesis. Our pioneer studies illuminate that SREBP2 – the master regulator of cholesterol biosynthesis – dictates hematopoietic stem and progenitor cell (HSPC) specification in development and HSPC expansion in hypercholesterolemia (Science2019). Lastly, our recent findings reveal that AIBP-mediated caveolae disruption facilitates signaling of VEGFR3 – the major pro-lymphangiogenesis receptor – by abating the inhibition of Caveolin1 on VEGFR3 (Yang X et al.,BioRxiv2020, manuscript in re-submission).
Built on these findings, we also investigate other key molecules of lipid metabolism and their regulation of angiogenesis, lymphangiogenesis, and hematopoiesis in development and disease. Furthermore, the Fang lab also actively pursues the translational potential of these findings because they provide new therapeutic components. Several patent applications of the Fang laboratory are pending. The Fang laboratory has a dream: that someday some of their findings will be clinically applicable to benefit patients.
The Fang laboratory philosophy:Equip yourself with the mindset of a marathon runnerbecause the scientific explorations at the edge of current knowledge limits are, most of the time, physically demanding and mentally stressful. We believe that “You never fail until you stop trying!” by Albert Einstein, provided that your experiments fail in the presence of proper quality controls. We learn to enjoy thethrillof previously unknown scientific findings – which satisfy our curiosities – more in our everyday endeavor, but less in not their final publications.

Areas Of Expertise

Angiogenesis Lymphangiogenesis hematopoiesis cholesterol metabolism
Education & Training

Postdoctoral Associate, University of California, San Diego
BS, Anhui Normal University
PhD, CAS - Shanghai Institute of Biochemistry and Cell Biology
Publications

Free Cholesterol Bioavailability and Atherosclerosis
Abe, RJ, Abe, JI, Nguyen, MTH, Olmsted-Davis, EA, Mamun, A, Banerjee, P, Cooke, JP, Fang, L, Pownall, H & Le, NT 2022, , Current Atherosclerosis Reports, vol. 24, no. 5, pp. 323-336. https://doi.org/10.1007/s11883-022-01011-z

Metabolic flexibility maintains proliferation and migration of FGFR signaling–deficient lymphatic endothelial cells
Song, H, Zhu, J, Li, P, Han, F, Fang, L & Yu, P 2021, , Journal of Biological Chemistry, vol. 279, no. 4, 101149. https://doi.org/10.1016/j.jbc.2021.101149

Metabolic flexibility maintains proliferation and migration of FGFR signaling-deficient lymphatic endothelial cells
Song, H, Zhu, J, Han, F, Fang, L & Yu, P 2021, , J Biol Chem, vol. 294, no. 4. https://doi.org/10.1016/j.jbc.2021.101149

Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice
Kim, JD, Zhu, L, Sun, Q & Fang, L 2021, , PLoS ONE, vol. 16, no. 4 April, e0248964. https://doi.org/10.1371/journal.pone.0248964

AIBP, Angiogenesis, Hematopoiesis, and Atherogenesis
Qiu, X, Luo, J & Fang, L 2021, , Current Atherosclerosis Reports, vol. 23, no. 1, 1. https://doi.org/10.1007/s11883-020-00899-9

Combination of apolipoprotein-A-I/apolipoprotein-A-I binding protein and anti-VEGF treatment overcomes anti-VEGF resistance in choroidal neovascularization in mice
Zhu, L, Parker, M, Enemchukwu, N, Shen, M, Zhang, G, Yan, Q, Handa, JT, Fang, L & Fu, Y 2020, , Communications Biology, vol. 3, no. 1, 386. https://doi.org/10.1038/s42003-020-1113-z

Hematopoiesis is regulated by cholesterol efflux pathways and lipid rafts: Connections with cardiovascular diseases
Morgan, PK, Fang, L, Lancaster, GI & Murphy, AJ 2020, , Journal of lipid research, vol. 61, no. 5, pp. 667-675. https://doi.org/10.1194/jlr.TR119000267

Regulation of lipid rafts, angiogenesis and inflammation by AIBP
Fang, L & Miller, YI 2019, , Current opinion in lipidology, vol. 30, no. 3, pp. 218-223. https://doi.org/10.1097/MOL.0000000000000596

AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate
Gu, Q, Yang, X, Lv, J, Zhang, J, Xia, B, Kim, JD, Wang, R, Xiong, F, Meng, S, Clements, TP, Tandon, B, Wagner, DS, Diaz, MF, Wenzel, PL, Miller, YI, Traver, D, Cooke, JP, Li, W, Zon, LI, Chen, K, Bai, Y & Fang, L 2019, , Science, pp. eaav1749. https://doi.org/10.1126/science.aav1749

TBX20 Regulates Angiogenesis Through the Prokineticin 2-Prokineticin Receptor 1 Pathway
Meng, S, Gu, Q, Yang, X, Lv, J, Owusu, I, Matrone, G, Chen, K, Cooke, JP & Fang, L 2018, , Circulation, vol. 138, no. 9, pp. 913-928. https://doi.org/10.1161/CIRCULATIONAHA.118.033939

AIBP augments cholesterol efflux from alveolar macrophages to surfactant and reduces acute lung inflammation
Choi, SH, Wallace, AM, Schneider, DA, Burg, E, Kim, J, Alekseeva, E, Ubags, ND, Cool, CD, Fang, L, Suratt, BT & Miller, YI 2018, , JCI insight, vol. 3, no. 16. https://doi.org/10.1172/jci.insight.120519

AIBP protects against metabolic abnormalities and atherosclerosis
Schneider, DA, Choi, SH, Agatisa-Boyle, C, Zhu, L, Kim, J, Pattison, J, Sears, DD, Gordts, PLSM, Fang, L & Miller, YI 2018, , Journal of lipid research, vol. 59, no. 5, pp. 854-863. https://doi.org/10.1194/jlr.M083618

A minimally invasive approach to induce myocardial infarction in mice without thoracotomy
Sun, Q, Wang, KK, Pan, M, Zhou, JP, Qiu, XT, Wang, ZY, Yang, Z, Chen, Y, Shen, H, Gu, QL, Fang, LH, Zhang, GG & Bai, YP 2018, , Journal of Cellular and Molecular Medicine, vol. 22, no. 11, pp. 5208-5219. https://doi.org/10.1111/jcmm.13708

Lmo2 (LIM-Domain-Only 2) Modulates Sphk1 (Sphingosine Kinase) and Promotes Endothelial Cell Migration
Matrone, G, Meng, S, Gu, Q, Lv, J, Fang, L, Chen, K & Cooke, JP 2017, , Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 37, no. 10, pp. 1860-1868. https://doi.org/10.1161/ATVBAHA.117.309609

AIBP Limits Angiogenesis Through ?-Secretase-Mediated Upregulation of Notch Signaling
Mao, R, Meng, S, Gu, Q, Araujo-Gutierrez, R, Kumar, S, Yan, Q, Almazan, F, Youker, KA, Fu, Y, Pownall, HJ, Cooke, JP, Miller, YI & Fang, L 2017, , Circulation Research, vol. 120, no. 11, pp. 1727-1739. https://doi.org/10.1161/CIRCRESAHA.116.309754

AIBP: A Novel Molecule at the Interface of Cholesterol Transport, Angiogenesis, and Atherosclerosis
Zhu, L & Fang, L 2015, , Methodist DeBakey cardiovascular journal, vol. 11, no. 3, pp. 160-165. https://doi.org/10.14797/mdcj-11-3-160

Polo-like kinase 2 regulates angiogenic sprouting and blood vessel development
Yang, H, Fang, L, Zhan, R, Hegarty, JM, Ren, J, Hsiai, TK, Gleeson, JG, Miller, YI, Trejo, JA & Chi, NC 2015, , Developmental Biology, vol. 404, no. 2, pp. 49-60. https://doi.org/10.1016/j.ydbio.2015.05.011

Apoc2 loss-of-function zebrafish mutant as a genetic model of hyperlipidemia
Liu, C, Gates, KP, Fang, L, Amar, MJ, Schneider, DA, Geng, H, Huang, W, Kim, J, Pattison, J, Zhang, J, Witztum, JL, Remaley, AT, Dong, PD & Miller, YI 2015, , DMM Disease Models and Mechanisms, vol. 8, no. 8, pp. 989-998. https://doi.org/10.1242/dmm.019836

Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of MicroRNA-92a
Chen, Z, Wen, L, Martin, M, Hsu, CY, Fang, L, Lin, FM, Lin, TY, Geary, MJ, Geary, GG, Zhao, Y, Johnson, DA, Chen, JW, Lin, SJ, Chien, S, Huang, HD, Miller, YI, Huang, PH & Shyy, JYJ 2015, , Circulation, vol. 131, no. 9, pp. 805-814. https://doi.org/10.1161/CIRCULATIONAHA.114.013675

Zebrafish models of dyslipidemia: Relevance to atherosclerosis and angiogenesis
Fang, L, Liu, C & Miller, YI 2014, , Translational Research, vol. 163, no. 2, pp. 99-108. https://doi.org/10.1016/j.trsl.2013.09.004