Michael Taylor

Position title: Assistant Professor

Email: michael.taylor@wisc.edu

School of Pharmacy, Pharmaceutical Sciences Division
Genetic dissection of blood-brain barrier development

777 Highland Ave.
PhD, University of Washington, Seattle, 2002
School of Pharmacy, Pharmaceutical Sciences Division
Research Interests
Genetic dissection of blood-brain barrier development
Research Fields
Zebrafish Genetics, Developmental Neurobiology, Cell Biology, Confocal Microscopy

Research Description:
The blood-brain barrier (BBB) remains poorly understood despite its important role in most diseases of the central nervous system (CNS). Functionally, the BBB provides the microenvironment necessary for proper neuronal function, while protecting the brain from potentially harmful substances. These restrictive properties also prevent the free exchange of many therapeutic agents, presenting a challenging problem for the treatment of neurological disorders. Furthermore, the BBB is often disrupted in CNS diseases including neurodegenerative disorders, brain tumors, stroke, epilepsy, and diabetic retinopathy. Given the clinical significance of the BBB, it is surprising how little is understood about the molecular mechanisms that regulate BBB formation and maintenance. This gap in fundamental knowledge could be closed by the development of an animal model suitable for in vivo imaging and high-throughput genetic and small molecule screening strategies. To solve this problem, we have generated transgenic zebrafish to visualize the BBB in vivo and to identify novel modulators of BBB function. The overall goal our research is to discover innovative strategies for drug delivery into the CNS.

Representative Publications:
Ju, B., Chen, W., Orr, B. A., Spitzbergen, Jia, S., Eden, C. J., Henson, H. E., Taylor, M. R. (2015). Oncogenic KRAS promotes malignant brain tumors in zebrafish. Molecular Cancer 14:18.

Henson, H. E., Parupalli, C., Ju, B., Taylor, M. R. (2014). Functional and genetic analysis of choroid plexus development in zebrafish. Frontiers in Neuroscience 8:364.

Eden, C. J., Ju, B., Murugesan, M., Phoenix, T., Nimmervoll, B., Tong, Y., Ellison, D. W., Lessman, C. A., Taylor, M. R.*, and Gilbertson, R. J.* (2014) Orthotopic models of pediatric brain tumors in zebrafish. Oncogene 34:1736-42. *Co-corresponding authors.

Wu,, G., Diaz, A. K., Paugh, B. S., Rankin, S. L., Ju, B., Li, Y., Zhu, X., Qu, C., Chen, X., Zhang, J., Easton, J., Edmonson, M., Ma, X., Lu, C., Nagahawatte, P., Hedlund, E., Rusch, M., Pounds, S., Lin, T., Onar-Thomas, A., Huether, R., Kriwacki, R., Parker, M., Gupta, P., Becksfort, J., Wei, L., Mulder, H. L., Boggs, K., Vadodaria, B., Yergeau, D., Russell, J. C., Ochoa, K., Fulton, R. S., Fulton, L. L., Jones, C., Boop, F. A., Broniscer, A., Wetmore, C., Gajjar, A., Ding, L., Mardis, E. R., Wilson, R. K., Taylor, M. R., Downing, J. R., Ellison, D. W., Zhang, J., and Baker, S. J. (2014) The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nature Genetics 46:444-50.

Ju, B., Chen, W., Spitsbergen, J. M. Lu, J., Vogel, P., Peters, J. L., Wang, Y. D., Henson, H. E., Jia, S., Parupalli, C., and Taylor, M. R. (2014) Activation of Sonic hedgehog signaling in neural progenitor cells promotes glioma development in the zebrafish optic pathway. Oncogenesis 3:e96.

Jia, S., Muto, A., Orisme, W., Henson, H. E., Parupalli, C., Ju, B., Baier, H., and Taylor, M. R. (2014) Zebrafish Cacna1fa is required for cone photoreceptor function and synaptic ribbon formation. Human Molecular Genetics 23:2981-94.

Quintana, A. M., Picchione, F., Klein Geltink, R. I., Taylor, M. R.*, and Grosveld, G. C.* (2013) Zebrafish etv7 regulates red blood cell development through the cholesterol synthesis pathway. Disease Models and Mechanisms 7:265-70. *Co-corresponding authors.

Muto, A.*, Taylor, M. R.*, Suzawa, M., Korenbrot, J. I., and Baier, H. (2013) Glucocorticoid receptor activity regulates light adaptation in the zebrafish retina. Frontiers in Neural Circuits 7:145. *Co-first authors.

Vrijens, K., Lin, W., Cui, J., Farmer, D., Low, J., Pronier, E., Zeng, F. Y., Shelat, A. A., Guy, K., Taylor M. R., Chen, T., and Roussel, M. F. (2013). Identification of small molecule activators of BMP signaling. PLoS One 8:e59045.

Umans, R. A. and Taylor, M. R. (2012). Zebrafish as a model to study drug transporters at the blood-brain barrier. Clin. Pharmacol. Ther. 92:567-70. (Cover Art)

Ju, B., Spitsbergen, J., Eden, C. J., Taylor, M. R., Chen, W. (2009). Co-activation of hedgehog and AKT pathways promotes tumorigenesis in zebrafish. Mol. Cancer 8:40-5.

Nevin, L. M., Taylor, M. R., and Baier, H. (2008). Hardwiring of fine synaptic layers in the zebrafish visual pathway. Neural Development 3:36-48.

Baraban, S. C., Dinday, M. T., Castro, P. A., Chege, S., Guyenet, S., and Taylor, M. R. (2007). A large-scale mutagenesis screen to identify seizure-resistant zebrafish. Epilepsia 48:1151-7.

Kennedy, B. N., Alvarez, Y., Brockerhoff, S. E., Stearns, G. W., Sapetto-Rebow, B., Taylor, M. R., and Hurley, J. B. (2007). Identification of a zebrafish cone photoreceptor-specific promoter and genetic rescue of achromatopsia in the nof mutant. Invest. Ophthalmol. Vis. Sci. 48:522-9.

Baraban, S. C., Taylor, M. R., Castro, P. A., and Baier, H. (2005). Pentylenetetrazole induced changes in zebrafish behavior, neural activity, and c-fos expression. Neuroscience 131:759-68. (Cover Art)

Taylor, M. R., Kikkawa, S., Ramamurthy, V., Kawakami, K., and Brockerhoff, S. E. (2005). The zebrafish pob gene encodes a novel protein required for survival of red cone photoreceptor cells. Genetics 170:263-73.

Taylor, M. R., Hurley, J. B., Van Epps, H. A., and Brockerhoff, S. E. (2004). A zebrafish model for pyruvate dehydrogenase deficiency: rescue of neurological dysfunction and embryonic lethality using a ketogenic diet. Proc. Natl. Acad. Sci. U S A 101:4584-9.

Brockerhoff, S. E., Rieke, F., Matthews, H. R., Taylor, M. R., Cilluffo, M. C., Fain, G. L., Ankoudinova, I., Xiao, M., Niemi, G. A., Tucker, C. L., and Hurley, J. B. (2003). Light stimulates a transducin-independent increase of cytoplasmic Ca2+ and a suppression of current in cones from the zebrafish mutant nof. J. Neurosci. 23:470-80. (Cover Art)