Education
Ph.D., Harvard University
Research
Membrane fusion initiates many important events including fertilization,
muscle development, synaptic transmission, and enveloped virus infections.
My laboratory has probed the mechanisms of proteins that mediate fusion,
and hence infection, by enveloped viruses including influenza virus and retroviruses.
A working hypothesis has been that similar proteins may be used during cell-cell
fusion events such as sperm-egg fusion. Based on an interest in sperm-egg fusion,
my laboratory cloned and sequenced fertilin alpha and beta in 1992
(Blobel et al. 1992. Nature. 356:248 252). Fertilin alpha and beta are sperm
surface proteins that are critically involved in fertilization. They are also the
founding members of the ADAM (a disintegrin and metalloprotease) family of
proteins (see the White Lab website for more information on ADAMs). As
outgrowths of these findings we have been exploring the interaction of ADAM
disintegrin domains with eggs. In the process we provided the first evidence that the
integrin-associated tetraspan protein, CD9, plays a pivotal role in the process of
sperm-egg fusion. Consistent with our conclusion, female mice lacking CD9 show
severely reduced fertility due to a block in sperm-egg fusion. We are currently
exploring the role of CD9 in sperm-egg fusion.
Representative Publications
1. Chen, M. S., Tung, K. S. K., Coonrod, S. A., Takahashi, Y., Bigler, D.,
Chang, A., Yamashita, Y., Kincade, P. W., Herr, J. C., and White, J. M.
(1999). Role of the integrin-associated protein CD9 in binding between
sperm ADAM 2 and the egg integrin a6b1: Implications for murine
fertilization. Proc. Nat'l. Acad. Sci. USA 96, 11830-11835.
2. Bigler, D., Takahashi, Y., Chen, M. S., Almeida, E. A. C., Osbourne,
L., and White, J. M. (2000). Sequence-specific interaction between the
disintegrin domain of mouse ADAM 2 (fertilin b) and murine eggs: Role
of the a6 integrin subunit. J. Biol. Chem. 275, 11576-11584.
3. Armstrong, R. T., Kushnir, A., and White, J. M. (2000). The
transmembrane domain of influenza hemagglutinin exhibits a stringent
length requirement to promote the hemifusion to fusion transition. J.
Cell Biol. 151, 425-438.
4 .Moss, M. L., White, J. M., Lambert, M. H., and Andrews, R. C. (2001).
TACE and other ADAM proteases as targets for drug discovery. Drug Disc.
Today 6, 417-426.
5. Takahashi, Y., Bigler, D., Ito, Y., and White, J. M. (2001).
Sequence-specific interaction between the disintegrin domain of mouse
ADAM 3 and murine eggs: role of the b1 integrin associated proteins
CD9, CD81 and CD98. Mol. Biol. Cell 12, 809-820.
6. White, J. M., and Rose, M. D. (2001). Yeast mating: Getting close to
membrane merger. Curr. Biol. 11, R16-R20. |
