Kopec, A; Abrahams, S; Thornton, S; Palumbo, J; Mullins, E; Divanovic, S; Weiler, H; III, O; Mackman, N; Goss, A; van Ryn, J; Luyendyk, J; Flick, M Thrombin promotes diet-induced obesity through fibrin-driven inflammation Journal of Clinical Investigation. 2017; 127(8):3152-3166.
In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet as well as obese patients. The results provide proof of concept that targeting thrombin or fibrinogen may limit pathologies in obese patients.
Sakabe, M; Fan, J; Odaka, Y; Liu, N; Hassan, A; Duan, X; Stump, P; Byerly, L; Donaldson, M; Hao, J; Fruttiger, M; Lu, Q; Zheng, Y; Lang, R; Xin, M YAP/TAZ-CDC42 signaling regulates vascular tip cell migration Proceedings of the National Academy of Sciences of the United States of America. 2017; 114(41):201704030-201704030.
The Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells during retinal angiogenesis. The findings from this work uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in endothelial cells regulates angiogenesis.
Lee, J; Govindarajah, V; Goddard, B; Hinge, A; Muench, D; Filippi, M; Aronow, B; Cancelas, J; Salomonis, N; Grimes, H; Reynaud, D Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression The Journal of Experimental Medicine. 2018; 215(2):627-644.
Obesity alters the composition of the hematopoietic stem cell compartment and its activity in response to hematopoietic stress. The impact of obesity on HSC function is progressively acquired but persists after weight loss or transplantation into a normal environment. This study provides phenotypic and mechanistic insight into durable hematopoietic dysregulations resulting from obesity.
Fang, J; Muto, T; Kleppe, M; Bolanos, L; Hueneman, K; Walker, C; Sampson, L; Wellendorf, A; Chetal, K; Choi, K; Salomonis, N; Choi, Y; Zheng, Y; Cancelas, J; Levine, R; Starczynowski, D TRAF6 Mediates Basal Activation of NF-kappa B Necessary for Hematopoietic Stem Cell Homeostasis Cell Reports. 2018; 22(5):1250-1262.
Hematopoietic-specific deletion of Traf6 resulted in impaired blood stem cell self-renewal and fitness, revealing its role uniting hematopoiesis, adaptive immune signaling, innate immune signaling, and NF-κB signaling through the IκB kinase beta-mediated NF-κB activation. TRAF6 is required for hematopoietic stem cell homeostasis by maintaining a minimal threshold level of IKKβ/NF-κB signaling.
He, X; Zhang, L; Queme, L; Liu, X; Lu, A; Waclaw, R; Dong, X; Zhou, W; Kidd, G; Yoon, S; Buonanno, A; Rubin, J; Xin, M; Nave, K; Trapp, B; Jankowski, M; Lu, Q A histone deacetylase 3-dependent pathway delimits peripheral myelin growth and functional regeneration Nature Medicine. 2018; 24(3):338-351.
Through small-molecule screening focusing on epigenetic modulators, histone deacetylase 3 was identified as a potent inhibitor of peripheral myelinogenesis. The HDAC3-TEAD4 network functions as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair.