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David R. Allred, Ph.D. |
Contact Information
Email: allredd(at)ufl.edu
Telephone: 352-392-2239 x5826 (office); x5832 or x5836 (lab)
Education
M.S., Biology, Wayne State University, Detroit, 1978
Ph.D., Cell Biology, University of California, Riverside, 1982
Postdoctoral: University of Colorado, 1983-1986; University of Florida, 1986-1988
Honors and Awards
- 1990, Outstanding Faculty Achievement and Performance Award, University of Florida
- 1995, C.E. Cornelius Young Investigator Faculty Research Award, University of Florida
- 1999, University of Florida Faculty Research Productivity Award. 2007, Editorial Board, Molecular and Biochemical Parasitology
Research Interests
Mechanisms of persistence in babesial parasites
The focus of the Allred Laboratory is to decipher mechanisms used by various blood-borne parasites to interact with their vertebrate hosts in order to establish and maintain infections. Our current primary focus is on mechanisms used by babesial parasites to survive and establish highly persistent infections in hosts that are immune to disease. We have chosen to focus on Babesia bovis, a bovine parasite that causes a devastating acute disease but which goes on to establish a generally asymptomatic persistent infection lasting many years. Early observations made by others showed that B. bovis-infected red blood cells (IRBCs) carrying mature parasites sequester in the vasculature of the deep organs, and that the surface of IRBCs becomes altered antigenically during parasite development. We have attempted to establish the bases for these behaviors. In the process, we have confirmed the observations of antigenic modification and demonstrated these changes were due to the expression of the parasite-derived protein, VESA1, on the IRBC membrane surface. We have demonstrated VESA1 to undergo rapid antigenic variation during the course of infection in an individual animal. The molecular genetic basis for antigenic variation in B. bovis is currently being pursued. To date, this has resulted in the identification and characterization of the ves multigene family comprised of ves1a and ves1b genes encoding VESA1a and probably 1b. We have since determined that B. bovis utilizes a mechanism of “segmental gene conversion” to construct mosaic ves genes from bits of many ves genes. The variability that can be generated in this way is staggering, and can explain how this parasite successfully evades ongoing antibody responses targeting the IRBC. We have subsequently demonstrated a connection between antigenic variation and sequestration, and the sensitivity of cytoadhesion to the presence of antibodies recognizing VESA1. These results explain the logic behind the seemingly incongruous connection of adhesion with a structurally variant protein.
Ongoing projects
We are currently studying the molecular basis for regulation of ves gene expression, whether and how this parasite might achieve monoallelic transcription of ves genes, and how ves switch rates may be controlled at the population level. At the same time, we are pursuing the identity of the endothelial receptors for B. bovis cytoadhesion, and are attempting to devise a strategy to immunize against the adhesive function despite great variability in VESA1 structure and antigenicity.
Selected Publications
- Allred, D.R., T.C. McGuire, G.H. Palmer, S. Lieb, T.M. Harkins, T.F. McElwain and A.F. Barbet. 1990. Molecular basis for surface antigen size polymorphisms and conservation of a neutralization-sensitive epitope in Anaplasma marginale. Proc. Natl. Acad. Sci. (U.S.A.) 87: 3220-3224.
- Allred, D.R., S.A. Hines and K.P. Ahrens. 1993. Isolate-specific parasite antigens of the Babesia bovis-infected erythrocyte surface. Mol. Biochem. Parasitol. 60: 121-132.
- Allred, D.R., R.M. Cinque, T.J. Lane and K.P. Ahrens. 1994. Antigenic variation of parasite-derived antigens on the surface of Babesia bovis-infected erythrocytes. Infect. Immun. 62: 91-98.
- O'Connor, R.M., T.J. Lane, S.E. Stroup, and D.R. Allred. 1997. Characterization of a variant erythrocyte surface antigen (VESA1) expressed by Babesia bovis during antigenic variation. Mol. Biochem. Parasitol. 89: 259-270.
- O'Connor, R.M., Long, J.A., and Allred, D.R. 1999. Cytoadherence of Babesia bovis-infected erythrocytes to bovine brain endothelial cells provides an in vitro model of sequestration. Infect. Immun. 67: 3921-3928.
- O'Connor, R.M. and Allred, D.R. 2000. Selection of Babesia bovis-infected erythrocytes for adhesion to endothelial cells co-selects for altered variant erythrocyte surface antigen isoforms. J. Immunol. 164: 2037-2045.
- Allred, D.R., J.M-R. Carlton, R.L. Satcher, J.A. Long, W.C. Brown, P.E. Patterson, R.M. O'Connor, and S.E. Stroup. 2000. The ves multigene family of Babesia bovis encodes components of rapid antigenic variation at the infected erythrocyte surface. Mol. Cell 5: 153-162.
- Allred, D.R. and Al-Khedery, B. 2004. Antigenic variation and cytoadhesion in Babesia bovis and Plasmodium falciparum: different logics achieve the same goals. Mol. Biochem. Parasitol. 134: 27-35.
- Al-Khedery, B. and Allred, D.R. 2006. Antigenic variation in Babesia bovis occurs through segmental gene conversion of the ves multigene family, within a bidirectional locus of active transcription. Mol. Microbiol. 59: 402-414.
- Allred, D.R. 2007. Dynamics of anemia progression and recovery in Babesia bigemina infection is unrelated to initiating parasite burden. Vet. Parasitol. 146: 170-174.