Harald JungeAssistant Professor
Porter room B359B
Explore Harald Junge's areas of research and more in Vivo
Molecular mechanisms of vascular development; vascular diseases of the retina.
Blood vessels mediate a wide range of essential biological functions, especially in transport and physiological integration, induction of developmental programs, and maintenance of stem cell niches. Furthermore, the progression of prevalent human diseases - for instance solid cancers and vascular diseases of the retina - depends on processes of neovascularization. Our laboratory integrates molecular and protein-biochemical methods, cell biology, mouse genetics, and tissue analysis to understand the signaling pathways and developmental processes that mediate angiogenesis, vascular guidance, and vascular quiescence. These efforts help us to understand how basic vascular biology is altered in vascular diseases.
Pathways currently under study include VLDLR (very low density lipoprotein receptor) signaling and Norrin induced FZD4 signaling (Norrin/β-catenin signaling) in retinal vascular development and disease. Loss of VLDLR function causes massive hypervascularization in the retina, a phenotype reminiscent of subforms of neovascular age related macular degeneration. We currently investigate the molecular role of VLDLR to understand this phenotype. Norrin/β-catenin signaling is required for the development of intraretinal capillaries and dysfunction of this pathway impairs or abolishes vision (e.g. in Norrie disease or familial exudative vitreoretinopathy). We study this pathway in order to: i) gain insight into the mechanism of Norrin/β-catenin signaling and the function of the auxiliary membrane protein TSPAN12, ii) understand the role of this pathway during retinal vascular morphogenesis, and iii) elucidate its role in vascular diseases of the retina.
TSPAN12 is a Norrin Co-Receptor that Amplifies Frizzled4 Ligand Selectivity and Signaling.
Lai MB, Zhang C, Shi J, Johnson V, Khandan L, McVey J, Klymkowsky MW, Chen Z, Junge HJ.
Cell Rep. 2017 Jun 27;19(13):2809-2822.
Norrin-induced Frizzled4 endocytosis and endo-lysosomal trafficking control retinal angiogenesis and barrier function.
Zhang C, Lai MB, Khandan L, Lee LA, Chen Z, Junge HJ.
Nat Commun. 2017 Jul 4;8:16050. doi: 10.1038/ncomms16050.
Neurite Mistargeting and Inverse Order of Intraretinal Vascular Plexus Formation Precede Subretinal Vascularization in Vldlr Mutant Mice.
Johnson V, Xiang M, Chen Z, Junge HJ.
PLoS One. 2015 Jul 15;10(7):e0132013.
TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling.
Junge, HJ, Yang, S, Burton, JB, Paes, K, Shu, X, French, DM, Costa, M, Rice, DS, and Ye, W Cell, 139(2):299-311. 2009
Calmodulin and Munc13 form a Ca2+ sensor/effector complex that controls short-term synaptic plasticity.
Junge, HJ, Rhee, J, Jahn, O, Varoqueaux, F, Spiess, J, Waxham, MN, Rosenmund, C, and Brose, N Cell, 118(3):389-401. 2004
Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming.
Betz, A, Thakur, P, Junge, HJ, Ashery, U, Rhee, JS, Scheuss, V, Rosenmund, C, Rettig, J, and Brose, N Neuron, 30(1):183-96. 2001