Research in my laboratory is focused on understanding the cellular and molecular mechanisms that regulate formation of the blood-brain barrier in the central nervous system ( CNS) using genetic approaches in mice, and the mechanisms of barrier breakdown in a variety of CNS diseases such as stroke and autoimmune diseases having symptoms that include blood-brain barrier failure, using genetic, molecular, cellular and imaging approaches. We have developed novel mouse strains that allow us to visualize changes in structural components of the blood-brain barrier, namely tight junctions and caveolae, in living animals for several CNS diseases (e.g. stroke and multiple sclerosis) in order to understand the cellular mechanisms underlying barrier impairment in these neurological disorders. In addition, we are investigating the role of Wnt/β-catenin signaling in development of the CNS vasculature and formation of the blood-brain barrier, and we are exploring the role of this pathway in repairing the barrier in diseases where its function is compromised (e.g. stroke and autoimmune disorders). Finally, we are investigating the mechanisms of immune cells entry into the CNS in a novel animal model for a neuropsychiatric disorder caused by multiple Streptococcus pyogenes infections, in order to understand how immune cells induce neurovascular, synaptic and behavioral deficits in the brain.
Mazzoni J., Cutforth T., and Agalliu D. (2015). Dissecting the role of smooth muscle cells versus pericytes in regulating cerebral blood flow using in vivo optical imaging. Neuron 87: 4-6. doi:10.1016/j.neuron.2015.06.024
Kurimoto S, Jung J, Tapadia M, Lengfeld J, Agalliu D, Waterman M, Mozaffar T, Gupta R. (2015). Activation of the Wnt/ß-catenin signaling cascade after traumatic nerve injury. Neuroscience 294:101-8. doi: 10.1016/j.neuroscience.2015.02.049.
Lengfeld J, Cutforth T, Agalliu D. (2014). The role of angiogenesis in the pathology of multiple sclerosis. Vascular Cell 28;6(1):23. doi: 10.1186/s13221-014-0023-6. eCollection 2014.
Knowland D., Arac A., Sekiguchi K.J., Hsu M., Lutz S.E., Perrino J., Steinberg G.K., Barres B.A., Nimmerjahn A., and Agalliu D (2014). Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. Neuron 82: 603-617.
Lutz S.E., Lengfeld J., and Agalliu D (2014). Stem cell-based therapies for multiple sclerosis: recent advances in animal models and human clinical trials. Regenerative Medicine 9 (2): 129-132.
Liu L, Eckert MA, Riazifar H, Kang DK, Agalliu D, Zhao W (2013). From blood to the brain: can systemically transplanted mesenchymal stem cells cross the blood-brain barrier? Stem Cells Int. 2013;2013:435093. doi: 10.1155/2013/435093. Epub 2013 Aug 12.
Liu S, Agalliu D, Yu C, Fisher M (2012). The role of pericytes in blood-brain barrier function and stroke. Current Pharmaceutical Design 18: 3653-62.
Shimomura Y*, Agalliu D*, Vonica A*, Luria V*, Wajid M, Baumer A, Belli S, Petukhova L, Schinzel A, Brivanlou AH, Barres BA and Christiano AM (2010). APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex. Nature 464: 1043-1047.
Daneman R, Rumah KR, Zhou L, Agalliu D, Cahoy JD, Kaushal A and Barres BA (2010). The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells. PLoS One 5: e13741.
Daneman R, Agalliu D, Zhou L, Kuhnert F, Kuo CJ and Barres BA (2009). Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis. Proc. Natl. Acad. Sci. USA 106: 641-646.
Emery B, Agalliu D, Cahoy JD, Watkins TA, Dugas JC, Mulinyawe SB, Ibrahim A, Ligon KL, Rowitch DH and Barres BA (2009). Identification of myelin-gene regulatory factor as a critical transcriptional regulator required for CNS myelination. Cell 138: 172-85.
Agalliu D, Takada S, Agalliu I, McMahon AP and Jessell TM (2009). Motor neurons with axial muscle projections specified by Wnt4/5 signaling. Neuron 61: 708-720.
Agalliu D and Schieren I (2009). Heterogeneity in the developmental potential of motor neuron progenitors revealed by clonal analysis of single cells in vitro. Neural Development 4: 2.
Masckauchan, NTH, Agalliu D, Vorontchikhina M, Ahn A, Parmalee NL, Li C, Khoo A, Tycko B, Brown AM and Kitajewski J (2006). Wnt5a signaling induces proliferation and survival of endothelial cells and expression of MMP-1 and Tie-2. Molecular Biology of the Cell 17: 5163-72.
Lieberam I*, Agalliu D*, Nagasawa T, Ericson J and Jessell TM (2005). A Cxcl12-Cxcr4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons. Neuron 47: 667-679.
Committees , Council, and Professional Society Memberships
2011 - Member, American Heart Association
2012 - Member, International Brain Barriers Society
2013 - Member, North American Vascular Biology Organization
2014 - Member, PANS Consortium Network
2015- Member, Society for Neuroscience
CNS angiogenesis, blood-brain barrier, endothelial cell, tight junctions, caveolae, stroke, multiple sclerosis, PANDAS, autoimmune diseases.