Anthony De Tomaso Website: De Tomaso Lab
Botryllus individuals undergo a natural transplantation reaction when they come into contact with other members of the same species. Using a combination of genetic, genomic and cell biological approaches, we are focused on understanding the molecular mechanisms which underlie this reaction, which is similar to the MHC-based allorecognition found in the vertebrates, and functionally resembles the way in which bone marrow transplants are recognized and rejected in mice and humans. This allorecognition system exists to prevent the transplant of blood-borne pluripotent stem cells, which once transferred can parasitize other genotypes, replacing their somatic and/or germline tissues. Parasitic abilities are genetically determined and autonomous to the cells themselves, and we are studying the mechanisms which underlie these properties. Transplanted stem cells are able to parasitize other individuals because the adult body plan of Botryllus is colonial, and has an asexual reproductive pathway that can regenerate adult individuals through an independent developmental program lacking any embryonic stages-the only chordate which can do so. The developmental pathways which control the expansion, differentiation, and patterning of asexual regeneration are unknown, and we are studying this process using a variety of techniques. Botryllus occupies a key position in vertebrate evolution, and these studies may provide insights into the origins of many chordate innovations. Selected Publications Tiozzo, S., Voskoboynik, A., Brown, F.B., and De Tomaso, A.W. (2008) A conserved role of the VEGF pathway in angiogenesis of an ectodermally-derived vasculature. Developmental Biology (IN PRESS). Voskoboynik, A., Simon-Blecher, N., Soev, Y., Rinkevich, B., De Tomaso, A.W., Ishizuka, K.J., and Weissman, I.L. (2007) Striving for normality: whole body regeneration through a series of abnormal generations. FASEB Journal 21:1335-1344. De Tomaso A.W. (2006) Allorecognition polymorphism versus parasitic stem cells. Trends in Genetics 22:485-490. De Tomaso A.W. Allorecognition polymorphism vs. parasitic stem cells. Trends in Genetics (IN PRESS) Spencer V.N., Passegue E., Ludington, W.B., Voskoboynik A., Mitchel, K., Weissman, I.L., and De Tomaso, A.W. (2006) fester, a candidate allorecognition receptor from a primitive chordate. Immunity 25:163-173. Laird, D.J. and De Tomaso A.W. (2005) Predatory stem cells in the non-zebrafish chordate, Botryllus schlosseri. Zebrafish 1:357-361. Laird, D.J., De Tomaso, A.W., and Weissman I.L. (2005) Stem cells are units of natural selection in a colonial ascidian. Cell 123:1351-1360. De Tomaso, A.W., Nyholm, S.V., Ishizuka, K.I., Palmeri, K.P., Ludington, W.B., Mitchel, K and Weissman, IL (2005). Isolation and characterization of a protochordate histocompatibility locus. Nature 438:454-459. De Tomaso, A. W., and Weissman, I. L. 2004. Evolution of protochordate allorecognition locus. Science 303: 977. Azumi, K*., DeSantis, R*., De Tomaso, A.W*., Rigoutsos, I*, et. al., (2003) Genomic analysis of immunity in a basal chordate and evolution of the vertebrate immune system: waiting for Godot. Immunogenetics 55:570-581 De Tomaso, A.W., and Weissman, I.L. (2003) Construction and characterization of large-insert genomic libraries (BAC and Fosmid) of Botryllus schlosseri and identification of BAC contigs within a histocompatibility locus. Marine Biotechnology 5:103-115. De Tomaso, A. W. and Weissman, I. L. 2003. Initial characterization of a protochordate histocompatibility locus. Immunogenetics 55: 480-490. Dehal, P. Satou, Y., Azumi, K., Branno, M., Campbell, B., Degnan, B., DeSantis, R., De Tomaso, A.W., et. al., (2002) The complete genome sequence of the ascidian, Ciona intestinalis: insights into the evolutionary origins of chordates and vertebrates Science 298:2157-2167. Laird, D. J., De Tomaso, A., Cooper, M. D., and Weissman, I. L. 2000. 50 million years of chordate evolution: seeking the origins of adaptive immunity. Proc. Nat. Acad. Sci., USA 97: 6924-6926. |
Tony De Tomaso received his Ph.D. from the Department of Cell Biology at Washington University. Research in his lab is based around the phenomenon of self/non-self recognition (allorecognition) in a primitive chordate organism, Botryllus schlosseri. This allorecognition reaction links a number of disparate fields, including immunology, stem cell, developmental, and evolutionary biology, and also has ecological consequences. Several unique aspects of the Botryllus life history make it a novel, experimentally accessible model organism to ask pertinent questions in these distinct disciplines.