ZFIN ID: ZDB-LAB-161213-1
Hoeppner Lab
PI/Director: Hoeppner, Luke
Contact Person: Hoeppner, Luke
Email: lhoeppner@hi.umn.edu
URL: http://www.hi.umn.edu/portfolio-items/luke-hoeppner/
Address: The Hormel Institute, University of Minnesota 801 16th Avenue NE Austin, MN 55912
Country: United States
Phone: 507-437-9623
Line Designation: None assigned


Development of zebrafish models of vascular permeability and cancer metastasis
VEGF induces vascular permeability in stroke, heart attack, and cancer leading to many pathophysiological consequences. Following cerebral or myocardial infarction, VEGF induces gaps between adjacent endothelial cells in ischemic tissue and the resulting vessel leakiness causes deleterious edema formation and tissue damage. In cancer, VEGF-mediated permeability promotes tumor angiogenesis and metastasis. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of permeability do not exist. We developed a heat-inducible VEGF transgenic zebrafish model through which vascular permeability can be monitored in real-time. Using this approach with gene silencing techniques, as well as knockout mice, we described a novel role of phospholipase Cβ3 (PLCβ3) as a negative regulator of VEGF-mediated vascular permeability by tightly regulating intracellular calcium release. We have also used this zebrafish model to elucidate the role of RhoC and other molecules in vascular homeostasis. The zebrafish vascular permeability model represents a straightforward method for identifying genetic regulators of VEGF-mediated vascular as promising targets for cancer, heart disease and stroke therapies. We also developed a zebrafish xenograft model of human cancer cell metastasis, which was used in two separate studies to support our findings from murine cancer models. Although beyond the scope of our zebrafish work, my research group studies the role of dopamine and VEGF signaling in lung cancer progression and drug resistance.

Alam, Sk. Kayum Post-Doc Astone, Matteo Post-Doc

Camillo, C., Facchinello, N., Villari, G., Mana, G., Gioelli, N., Sandri, C., Astone, M., Tortarolo, D., Clapero, F., Gays, D., Oberkersch, R.E., Arese, M., Tamagnone, L., Valdembri, D., Santoro, M.M., Serini, G. (2021) LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion. The Journal of cell biology. 220(11):
Ganaie, A., Beigh, F.H., Astone, M., Ferrari, M.G., Maqbool, R., Umbreen, S., Parray, A.S., Siddique, H.R., Hussain, T., Murugan, P., Morrissey, C., Koochekpour, S., Deng, Y., Konety, B.R., Hoeppner, L.H., Saleem, M. (2018) BMI1 Drives Metastasis of Prostate Cancer in Caucasian and African-American Men and Is A Potential Therapeutic Target: Hypothesis Tested in Race-specific Models.. Clinical cancer research : an official journal of the American Association for Cancer Research. 24(24):6421-6432
Astone, M., Lai, J.K.H., Dupont, S., Stainier, D.Y.R., Argenton, F., Vettori, A. (2018) Zebrafish mutants and TEAD reporters reveal essential functions for Yap and Taz in posterior cardinal vein development. Scientific Reports. 8:10189
Astone, M., Dankert, E.N., Alam, S.K., Hoeppner, L.H. (2017) Fishing for cures: The alLURE of using zebrafish to develop precision oncology therapies. NPJ precision oncology. 1
Astone, M., Pizzi, M., Peron, M., Domenichini, A., Guzzardo, V., Töchterle, S., Tiso, N., Rugge, M., Meyer, D., Argenton, F., Vettori, A. (2015) A GFP-Tagged Gross Deletion on Chromosome 1 Causes Malignant Peripheral Nerve Sheath Tumors and Carcinomas in Zebrafish. PLoS One. 10:e0145178
Hoeppner, L.H., Sinha, S., Wang, Y., Bhattacharya, R., Dutta, S., Gong, X., Bedell, V.M., Suresh, S., Chun, C.Z., Ramchandran, R., Ekker, S.C., Mukhopadhyay, D. (2015) RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cells. Journal of Cell Science. 128(19):3556-68
Thakur, R.K., Yadav, V.K., Kumar, A., Singh, A., Pal, K., Hoeppner, L., Saha, D., Purohit, G., Basundra, R., Kar, A., Halder, R., Kumar, P., Baral, A., Kumar, M.M., Baldi, A., Vincenzi, B., Lorenzon, L., Banerjee, R., Kumar, P., Shridhar, V., Mukhopadhyay, D., Chowdhury, S. (2014) Non-metastatic 2 (NME2)-mediated suppression of lung cancer metastasis involves transcriptional regulation of key cell adhesion factor vinculin. Nucleic acids research. 42(18):11589-600
Cao, Y., Hoeppner, L., Bach, S., E, G., Guo, Y., Wang, E., Wu, J., Cowley, M.J., Chang, D.K., Waddell, N., Grimmond, S.M., Biankin, A.V., Daly, R.J., Zheng, X., and Mukhopadhyay, D. (2013) Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial alpha5 integrin. Cancer research. 73(14):4579-4590
Moro, E., Vettori, A., Porazzi, P., Schiavone, M., Rampazzo, E., Casari, A., Ek, O., Facchinello, N., Astone, M., Zancan, I., Milanetto, M., Tiso, N., and Argenton, F. (2013) Generation and application of signaling pathway reporter lines in zebrafish. Molecular genetics and genomics : MGG. 288(5-6):231-242
Hoeppner, L.H., Phoenix, K.N., Clark, K.J., Bhattacharya, R., Gong, X., Sciuto, T.E., Vohra, P., Suresh, S., Bhattacharya, S., Dvorak, A.M., Ekker, S.C., Dvorak, H.F., Claffey, K.P., and Mukhopadhyay, D. (2012) Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability. Blood. 120(11):2167-2173