UA Life Science Research - BioGate


David A Elliott

Assistant Professor


David Elliott Contact Information

Address: 1501 N. Campbell Ave.
PO Box 245044
Tucson, AZ 85724-5044
Phone: 520-626-7870
E-Mail: Elliott@arizona.edu

Degrees
Department Affiliations
Program Affiliations
Research Areas

Additional Information

Research Interests

Half a billion people will come down with malaria this year. Two people will die of it each minute. Most of these people will be children. The parasite is increasingly resistant to the drugs he have and all of the new drugs available are too expensive to be used by most of the worlds population. Nutrient uptake by the malaria parasite represents one of the greatest potential drug targets. There are two projects currently being worked on in the lab. The first is looking at the uptake of hemoglobin. The second project is looking at all of the Rab family of proteins and their role in regulating endocytosis/exocytosis. All of the pathology caused by the parasite is caused during its life cycle inside of the red blood cells. During this stage the parasite ingests massive amounts of hemoglobin. Digestion of hemoglobin provides the parasite with needed amino acids as well as other undefined functions. To measure hemoglobin uptake by the parasite, we have developed an assay using 3 dimensional reconstructions of serial transmission electron micrographs. Using this tool we have analyzed over 450 parasites and over 50 complete infected-Red Blood Cells. This standard data set makes it possible to investigate the effects of different treatments on the parasite to a degree of precision never before possible. Analysis of 3D reconstructions can differentiate between decreased uptake due to slower growth and decreased uptake due to altered kinetics of a process. By treating with drugs and the addition of dominant negative protein constructs we have begun to dissect the molecular players in the hemoglobin uptake pathway. Contrary to all expectations, we have shown that actin is not involved in the initial endocytic process, but is involved in the transport of the hemoglobin containing vacuoles to the parasite's food vacuole. We have shown that a specific Rab (Rab5a) localizes to the surface of the hemoglobin containing vacuoles, as seen by immuno-EM. A stably expressed dominant negative protein alters the morphology of the uptake process. This finding links the two projects in the lab. The second project in the lab involves an international collaboration to clone and identify the functions of the Rab proteins. As part of this project our Paris collaborator is knocking out and creating mutants of all of the Rabs using a rodent malaria model. Our Alabama collaborator will be doing the X-ray crystal structure of the important and interesting Rabs and we will be identifying the function and interactions of the Rabs and the yet to be discovered interacting proteins. Parasites present two very powerful reasons to study them. The first is the obvious desire to learn about them so that we can kill them. This work has the potential to save millions of people each year. The second reason to study these organisms has to do with their location on the tree of life. These parasites are among the earliest branching eukaryotes. These organisms have, through the ages, stripped themselves of everything that is not needed for their specific lifestyle. This makes them very good at a small number of processes. They have very few proteins involved in processes that are much more complex in 'higher' organisms. Thus in studying these organisms we have a window both into the early development of life, but also a very much simplified system to study the functions of humans.

Awards and Honors

2002 - Award for poster in basic research (open to all departmental students and fellows) in Johns Hopkins School of Medicine Department of Pathology Young Investigator Day competition
2001 - J. Howard Brown Award for the outstanding Graduate Student in Microbiology 2000 - 2001 American Society for Microbiology, Maryland Chapter
2001 - Manuscript Competition winner (graduate student division) American Society for Microbiology, Maryland Chapter
2001 - First place (3rd and 4th year graduate student category) in Johns Hopkins School of Medicine Graduate Student Association Poster competition
2001 - Award for poster in basic research (open to all departmental students and fellows) in Johns Hopkins School of Medicine Department of Pathology Young Investigator Day competition
2000 - Second place (3rd year graduate student category) in Johns Hopkins School of Medicine Graduate Student Association Poster competition
2000 - Award for poster in basic research (open to all departmental students and fellows) in Johns Hopkins School of Medicine Department of Pathology Young Investigator Day competition

Books

DA Elliott and FD Lowy. 2000. Studying Bacterial Adherence to Endothelial Cells. In the Handbook of Bacterial Adhesion: Principles, Methods, and Applications, Chap. 30. Humana Press, Totowa, NJ.

Organizations

American Association for the Advancement of Science American Society for Cell Biology American Society for Microbiology

Postdoctoral Training

2002 - 2004 Yale University School of Medicine, Post Doctoral Fellow in the laboratory of Dr. Keith Joiner researching Nutrient Uptake by Plasmodium falciparum

Complete List of Publications

D.A. Elliott. 2007. Serial Sectioning via Microtomy. Microscopy Today January:30-33.
K.M. Massimine, M.T. McIntosh, L.T. Doan, C.E. Atreya, S. Gromer, W. Sirawaraporn, D.A. Elliott, K.A. Joiner, R.H. Schirmer, and K.S. Anderson. 2006. Eosin B as a Novel Antimalarial Agent for Drug Resistant Plasmodium falciparum. Antimicrobial Agents and Chemotherapy, 50:3132-41.
M.T. McIntosh, D.A. Elliott and K.A. Joiner. 2005. Plasmodium falciparum: discovery of peroxidase active organelles. Exp Parasitol, 111:133-136.
D.A. Elliott, D.P. Clark. 2003. Host Cell Fate Upon Cryptosporidium parvum Egress from MDCK Cells. Infect. Immun., 71:5422-5426.
D.A. Elliott, D.J. Coleman, M.A. Lane, R.C. May, L.M. Machesky and D.P. Clark. 2001. Cryptosporidium parvum Infection Requires Host Cell Actin Polymerization. Infect. Immun., 69:5940-5942.
D.A. Elliott and D.P. Clark. 2000. Cryptosporidium parvum Induces Host Cell Actin Accumulation at the Host-Parasite Interface. Infect. Immun., 68:2315-2322.
A.P. Andersen, D.A. Elliott, M. Lawson, P. Barland, V.B. Hatcher and E.G. Puszkin. 1997. Growth and Morphological Transformations of Helicobacter pylori in Broth Media. Journal of Clin. Micro., 35:2918-2922.
K.A. Holbrook, R.S. Klein, D. Hartel, D.A. Elliott, T.B. Barsky, L.H. Rothschild and F.D. Lowy. 1997. Staphylococcus aureus Nasal Colonization in HIV Seropositive and Seronegative Drug Users. J. Acquired Immune Defic. Syndromes and Human Retroviral., 16:301-306.
W.K. Alston, M.E. Epstein, V.B. Hatcher, D.A. Elliott, M. Tang and F.D. Lowy. 1997. Extracellular Matrix Modulates Staphylococcus aureus Infection of Endothelial Cells. J. of Cellular Phys., 173:102-109.
D.C. Tompkins, L.H. Blackwell, V.B. Hatcher, D.A. Elliott, C. O’Hagan-Sotsky, and F.D. Lowy. 1992. Staphylococcus aureus Proteins That Bind to Human Endothelial Cells. Infect. Immun. 60:965-969.
D.A. Elliott, V.B. Hatcher, and F.D. Lowy. 1991. A 220-Kilodalton Glycoprotein in Yeast Extract Inhibits Staphylococcus aureus Adherence to Human Endothelial Cells. Infect. Immun. 59:2222-2223.

Teaching

In the Spring semester I teach CBA-565a, Fundamentals of Light Microscopy

Selected Publications

Gligorijevic B, Purdy K, Elliott DA, Cooper RA, Roepe PD. Jan 2008. Stage independent chloroquine resistance and chloroquine toxicity revealed via spinning disk confocal microscopy. Mol Biochem Parasitol.,

Elliott DA, McIntosh MT, Hosgood HD, Chen S, Zhang G, Baevova P, and Joiner KA. Feb 2008. Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum. PNAS, 105:2463-2468

Elliott, DA. Jan 2007. Serial Sectioning via Microtomy. Microscopy Today, 15:30-33

Massimine KM, McIntosh MT, Doan LT, Atreya CE, Gromer S, Sirawaraporn W, Elliott DA, Joiner KA, Schirmer RH, Anderson KS.. Sep 2006. Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum.. Antimicrob Agents Chemother., 50:3132-41


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