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Education

Ph.D., Harvard University

Research Interests

• Lab: Irvine 303/316
• Genetic regulation of mammalian neurovascular development, physiology and pathophysiology

Interdependent development and functions of the mammalian nervous and vascular systems are tightly coordinated. The brain vasculature provides a critical and expansive blood supply to support neuronal metabolism and function, and vascular lesions within the brain are often accompanied by neurological dysfunction. Our lab is interested in understanding how these systems influence one another – e.g., how diverse neural and vascular cell populations respond to cues from one another. The lab currently studies neurovascular regulation in the context of brain arteriovenous malformation (AVM), a human vascular disease characterized by direct delivery of blood from artery to vein (without intervening capillaries), vessel entanglements, and often accompanied by neurological deficit. We are using genetic models of brain AVM to determine molecular and cellular mechanisms that regulate neurovascular development and function – and mechanisms involved in neurovascular pathogenesis – using mouse genetics, molecular and cell biological, and imaging approaches.

Representative Publications

Nakisli, S., Lagares, A., Nielsen, C.M.* and Cuervo, H.* (2023). Pericytes and vascular smooth muscle cells in central nervous system arteriovenous malformations. Front Physiol 14. doi: 10.3389/fphys.2023.1210563. PMID: 37601628

Adhicary, S., Fanelli, K., Nakisli, S., Ward, B., Pearce, I. and Nielsen, C.M. (2023). Rbpj deficiency disrupts vascular remodeling via abnormal Apelin and Cdc42 activity in brain arteriovenous malformation. Stroke 54. doi: 10.1161/STROKEAHA.122.041853

Nielsen, C.M.*, Zhang, X.*, Rangor, K., Wang, S. and Wang, R.A. (2022). Endothelial Rbpj normalizes Notch4-induced brain arteriovenous malformation in mice. J Exp Med 220(2): e20211390. doi: 10.1084/jem.20211390. PMID: 36441145. *Equal contribution

Adhicary, S., Nakisli, S., Fanelli, K. and Nielsen, C.M. (2022). Neurovascular development. Encyclopedia of Child and Adolescent Health. Elsevier Publishing. ISBN: 978-0-12-818872-9. doi: 10.1016/B978-0-12-818872-9.00106-0

Song, J., Qian, Y, Evers, M., Nielsen, C.M. and Chen, X. (2022). Cancer stem cell formation induced and regulated by extracellular ATP and stanniocalcin-1 in human lung cancer cells and tumors. Int J Mol Sci 23: 14770. doi: 10.3390/ijms232314770.

Selhorst, S.*, Nakisli, S.*, Kandalai, S., Adhicary, S. and Nielsen, C.M. (2022). Pathological pericyte expansion and impaired endothelial cell-pericyte communication in endothelial Rbpj deficient brain arteriovenous malformation. Frontiers in Human Neuroscience. doi: 10.3389/fnhum.2022.974033. PMID: 36147294. *Equal contribution

Chapman, A.D., Selhorst, S., LaComb, J., LeDantec-Boswell, A., Wohl, T.R., Adhicary, S. and Nielsen, C.M. (2022). Endothelial Rbpj is required for cerebellar morphogenesis and motor control in the early postnatal mouse brain. Cerebellum doi: 10.1007/s12311-022-01429-w. PMID: 35716334

Nielsen, C.M.*, Qian, Y*., Adhicary, S., Li, Y., Shriwas, P., Wang, X., Bachmann, L. and Chen, X. (2021). ATP internalization, mediated by macropinocytosis and examined by fluorescence microscopy, in human tumor cells and in tumor-xenografted mice. J Vis Expts. doi: 10.3791/62768. PMID: 34279488. *Equal contribution

Shriwas, P., Roberts, D., Li, Y., Wang, L., Qian, Y., Bergmeier, S., Hines, J., Adhicary, S., Nielsen, C. and Chen, X. (2021). A small molecule pan-class I glucose transporter inhibitor reduces cancer cell proliferation in vitro and tumor growth in vivo by targeting glucose-based metabolism. Cancer & Metabolism 9(14). PMID: 33771231nie

Cuervo, H., Nielsen, C.M., Simonetto, D.A., Ferrell, L., Shah, V.H. and Wang, R.A. 2016. Endothelial Notch signaling is essential to prevent hepatic vascular malformation in mice. Hepatology 64(4):1302-1316.

Nielsen, C.M., Huang, L., Murphy, P.A., Lawton, M.T. and Wang, R.A. 2016. Mouse models of cerebral arteriovenous malformations. Stroke 47:293-300.

Murphy, P.A., Kim, T.N., Huang, L., Nielsen, C.M., Lawton, M.T., Adams, R.H., Schaffer, C.B. and Wang, R.A. 2014. Constitutively active Notch4 elicits brain arteriovenous malformations through enlargement of capillary-like vessels. Proceedings of the National Academy of Sciences USA 111:18007-18012.

Nielsen, C.M., Cuervo, H., Ding, V.W., Kong, Y., Huang, E.J. and Wang, R.A. 2014. Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice. Development 141:3782-3792.

Nielsen, C.M. and Dymecki, S.M. 2010. Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus. Developmental Biology 340:430-437.