David R Allred

David R Allred

Professor

Department: Department of Infectious Diseases & Immunology
Business Phone: (352) 294-4126
Business Email: allredd@ufl.edu

Accomplishments

Editorial Board
2008 · Eukaryotic Cell
Editorial Board
2007 · Molecular and Biochemical Parasitology
Editorial Board
2007 · The Open Parasitology Journal
Faculty Research Productivity Award
1999 · University of Florida
Outstanding Faculty Achievement and Performance Award
1995 · University of Florida
C.E. Cornelius Young Investigator Faculty Research Award
1990 · University of Florida

Research Profile

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.

Ongoing projects

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.

Open Researcher and Contributor ID (ORCID)

0000-0001-9347-5918

Publications

2012 Javma-Journal of the American Veterinary Medical Association

Grants

Mar 2017 – Apr 2019
Investigation of a shipworm endosymbiont compound with activity against the AIDS-associated pathogens Cryptosporidium and Toxoplasma
WASHINGTON STATE UNIV · Principal Investigator
May 2016 – Dec 2016
investigation of a shipworm endosymbiont compound with
TUFTS MEDICAL CENTER · Principal Investigator

Education

Postdoctoral
1986-1988 · University of Florida
Postdoctoral
1983-1986 · University of Colorado
PhD, Cell Biology
1982 · University of California – Riverside
MS, Biology
1978 · Wayne State University

Contact Details

Phones:
Business:
(352) 294-4126
Emails:
Business:
allredd@ufl.edu

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