Education & Training
- Ph.D. in Environmental Toxicology from University of Wisconsin Madison, 1997
- B.S. in Biochemistry from Penn State, 1989
Research Interest Summary
Generally, arteries are connected to veins via intervening capillaries. However, in rare cases, an artery may connect directly to a vein. These arteriovenous malformations (AVMs), which affect about 300,000 Americans, can deprive surrounding tissue of oxygen and nutrients and are prone to rupture, potentially leading to hemorrhage or stroke. My laboratory uses zebrafish embryos as a tool to uncover the molecular and biomechanical factors and cellular behaviors that underlie these malformations. Zebrafish develop a stereotypical vertebrate vasculature, the formation of which is guided by the same molecular cues that guide mammalian vascular development. And zebrafish embryos are externally fertilized, optically transparent, and fast-developing, allowing us to noninvasively watch vessels – and AVMs – form in real time.
Current work in the laboratory employs molecular, genetic, advanced imaging, and biochemistry techniques to define the factors that lead to AVMs in zebrafish embryos harboring mutations in acvrl1. ACVRL1 encodes a TGF-βfamily type I serine/threonine kinase receptor, heterozygous mutations in which underlie the human AVM disease, hereditary hemorrhagic telangiectasia type 2 (HHT2). Our goals include defining the molecular pathway by which ACVRL1 signals within the endothelium, uncovering the biochemical and biomechanical factors that control ACVRL1 expression, and describing the effect of pathway activation on endothelial cell behavior, thereby gaining insight into potential therapeutic targets for HHT2.
Laux, D.W., Febbo, J.A., and Roman, B.L. (2011). Dynamic Analysis of BMP-Responsive Smad Activity in Live Zebrafish Embryos. Devel. Dyn. 240, 682-694.
Corti, P., Young, S., Chen, C.Y., Patrick, M.J., Rochon, E.R., Pekkan, K., and Roman, B.L. (2011). Interaction between alk1 and blood flow in the development of arteriovenous malformations. Development 138, 1573-1582. PMCID: PMC3062425.
Fujita, M., Cha, Y., Pham, V.N., Sakurai, A., Roman, B.L., Gutkind, J.S., and Weinstein, B.M. (2011). Assembly and patterning of the vascular network of the vertebrate hindbrain. Development 138, 1705-1715. PMCID: PMC3074447.
Chen, C.Y., Patrick, M.J., Corti, P., Kowalski, W., Roman, B.L., and Pekkan, K. (2011). Analysis of early embryonic great vessel microcirculation in zebrafish using high-speed confocal μPIV. Biorheology 48, 305-321.
Roman, B.L. and Pekkan, K. (2012). Mechanotransduction in embryonic vascular development. Biomech. Mod. Mechanobiol. 11, 1149-1168.
Kim, J.D., Kang, H., Larrivee, B., Lee, M.Y., Mettlen, M., Schmid, S.L., Roman, B.L., Qyang, Y., Eichmann, A., and Jin, S.W. (2012). Context-dependent proangiogenic function of bone morphogenetic protein signaling is mediated by disabled homolog 2. Devel. Cell 23, 441-448. PMCID: PMC3659797.
Watkins, S.C, Maniar, S., Mosher, M., Roman, B.L., Tsang, M., and St. Croix, C.M. (2012). High resolution imaging of vascular function in zebrafish. PLoS One 7, e44018. DOI 10.1371/journal.pone.0044018. PMCID: PMC3431338.
Laux, D.W., Young, S., Donovan J.P., Mansfield, C.J., Upton, P.D., and Roman, B.L. (2013). Circulating Bmp10 acts through endothelial Alk1 to mediate flow-dependent arterial quiescence. Development 140, 3403-3412.
Wooderchuk-Donahue, W.L., McDonald, J., O’Fallon, B., Upton, P.D., Li, W., Roman, B.L., Young, S., Plant, P., Fulop, G., Langa, C., Morrell, N.W., Botella, L.M., Bernabeu, C., Stevenson, D.A., Runo, J.R., and Bayrak-Toydemir, P. (2013). BMP9 mutations cause a vascular anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia. Am. J. Hum. Gen. 93, 530-537.
Lee, J., Esmaily Moghadam, M., Kung, E., Cao, H., Beebe, T., Miller, Y.I., Roman, B.L., Lien, C.L., Chi, N.C., Marsden, A.L., and Hsiai, T. (2013). Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis. PLoS One 8, e72924 do1:10.1371/journal.pone.0072924. PMCID: PMC3751826.