David R. Allred
Department of Infectious Diseases & Immunology
PO Box 110880
2015 SW 16th AV
Gainesville, FL 33611-0880
352-294-4136 or 294-4132 (labs)
- MS, Biology, Wayne State University, Detroit, 1978
- PhD, Cell Biology, University of California, Riverside, 1982
- Postdoctoral, University of Colorado, 1983-1986; University of Florida, 1986-1988
Honors and Awards
- C.E. Cornelius Young Investigator Faculty Research Award, University of Florida, 1990
- Outstanding Faculty Achievement and Performance Award, University of Florida 1995
- University of Florida Faculty Research Productivity Award, 1999
- Editorial Board, Molecular and Biochemical Parasitology, 2007
- Editorial Board, The Open Parasitology Journal, 2007
- Editorial Board, Eukaryotic Cell, 2008
Mechanisms of persistence in babesial parasites
The long-term goal of the Allred Laboratory is to find the means to protect animals and humans from the pathology of parasitic infection. The approach we have taken is to identify mechanisms used by blood-borne parasites to interact with their vertebrate hosts in order to establish and maintain persistent 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 make the bovine pathogen, Babesia bovis, our primary study target, in part because it shares many biological parallels with the human malarial parasite, Plasmodium falciparum.
B. bovis is a bovine parasite that causes a devastating acute disease but which goes on to establish a generally asymptomatic persistent infection lasting many years. During the persistent infection, the surface of IRBCs becomes altered antigenically during parasite development, and B. bovis-infected red blood cells (IRBCs) carrying mature parasites sequester in the vasculature of the deep organs, sometimes leading to highly lethal cerebral babesiosis. We are investigating the bases for these linked behaviors. In the process, we have demonstrated these changes are due, at least in part, to the expression of parasite-derived proteins, particularly VESA1, on the IRBC membrane surface. VESA1 mediates cytoadhesion, allowing mature IRBCs to sequester in the deep organs. We have shown the sensitivity of cytoadhesion to the presence of antibodies recognizing VESA1, opening up the possibility of immunizing animals to protect from the pathology of this disease. However, this is complicated by the fact that VESA1 also undergoes rapid antigenic variation during the course of infection in an individual animal, rendering pre-existing antibodies ineffective. Our studies on the molecular genetic basis for antigenic variation in B. bovis have resulted in the identification and characterization of the ves multigene family encoding VESA1 subunits. We have determined that B. bovis employs “segmental gene conversion” to construct mosaic ves genes from bits of many ves genes, and are currently identifying the enzymatic machinery mediating this. The variability in antigenicity and function that can be generated in this way is staggering, and helps to explain how this parasite successfully evades ongoing antibody responses targeting the IRBC.
We are currently studying the molecular basis for regulation of ves gene expression, as well as the enzymatic machinery required for gene conversion events in antigenic variation. Moreover, we are collaborating on detection of the mechanisms enabling intracellular parasites to export proteins such as VESA1 and Smorf out into the infected host cell. We are also collaborating on a related project with the bacterial pathogen, Anaplasma phagocytophilum. Currently, we are studying the enzymatic machinery responsible for DNA repair, including segmental gene conversion, to identify logical targets for their lethal disruption. In a parallel approach, we have been involved in non-targeted drug studies to identify novel drugs that might be used to treat babesial infections, and have found candidates for further exploration. We look forward to the implementation of one or more of these approaches in the future.
Additional publications here