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  Audrey Lau    
         
  Audrey O. T. Lau, MPH, PhD
Assistant Research Professor

Research Interests

My primary research interests focus on host-microbe interactions, specifically on the regulatory mechanisms of gene expression in protozoa, using Babesia bovis as the model system. B. bovis is a member of the Apicomplexan phylum in which Plasmodium, the malaria parasite, is a member. This parasite is intraerythrocytic and is responsible for substantial economic losses in the cattle industry in the tropical and subtropical regions of the world where the vector host, Boophilus microplus, resides. A live attenuated vaccine is currently available for most parts of the world where babesiosis is endemic. Unfortunately, the vaccine consists of population of B. bovis that when passage through intact animals or tick vector, attenuation can be lost. As a result, breakthrough strains of B. bovis occur in immunized cattle. The underlying mechanism for the selection of one isolate over another in such population when exposed to intact animals is currently unknown. It is also not known what interactions exist between the tick host and the parasites to allow the preferential selection of virulent isolates through the vector host. A better knowledge of the relationship between the two hosts and B. bovis not only will give us insights into methods of improving current vaccine strategies, but will also enable us to understand more in depth relationship between the hosts and the parasite. With the availability of the data generated from the B. bovis genome project, a high density oligonucleotide microarray system was constructed to document the expression profiles of life cycle stages. To date, the blood stage array was successful and thus, a gene expression profile of a virulent B. bovis strain is established.

I am also interested in the evolution of microbial organelles. Similar to Plasmodium, Babesia consists of two extrachromosomal organelles – mitochondrion and apicoplast. According to the established theorum, evolution of oxygenic eukaryotic photoautotrophs gave rise to 3 groups, glaucophyta (chlorophyll a), green algae (chlorophyll b) and their descendents, land plants and red algae (chlorophyllide c). Molecular phylogenetic data have strong support that a single origin that gave rise to the 3 primary plastid containing algae and that a cyanobacteria was the organism that was engulfed by an ancient eukaryote. When it comes to how the secondary endosymbiosis came about, this issue becomes more controversial. In collabortion with Eric Roalson (collaborator), 9 apicoplast-located genes from a total of 28 phyla was analyzed, the most extensive phylogenetic analysis to determine the origin of this organelle. Our results clearly refute the current chromalveolate theorum, which states that apicoplasts have a red algal origin. Using both amino and nucleic acid sequences, maximum likelihood analyses with both ML bootstrap and Bayesian interference posterior probability were carried out.

Selected Publications: (All)

1. Nicoll CS, Russell SM, Lau AOT. "Animal Liberation": An Exchange in The New York Reviews of Books, November 5, 1992; pp. 59-60.

2. Rodgers BD, Lau AOT, Nicoll CS. Hypophysectomy or Adrenalectomy of Rats with Insulin-Dependent Diabetes Mellitus Partially Restores Their Responsiveness to Growth Hormone. Proceedings of the Society for Experimental Biology and Medicine (Nov., 1994) 207(2): 220-226.

3. Magowan CC, Coppel R, Lau AOT, Moronne M, Narla M. Plasmodium falciparum mature Erythrocyte Surface Antigen: Effects on Parasite Growth, and Cytoadherence, and its Localization in Erythrocytes Deficient in Cytoskeletal Protein 4.1. Blood (Oct., 1995) 86(8): 3196-3204.

4. Lau AOT, Sacci Jr., JB, Azad, AF. Differential expression of Plasmodium yoelii genes. IX International Congress of Parasitology (Aug., 1998): 991-996.

5. Radulovic S, Troyer JM, Beier M, Lau AOT, Azad AF. Cloning of the Gene and Characterization of Rickettsia typhi Hemolysin. Infection and Immunity (Nov., 1999) 67 (11): 6104-6108.

6. Lau AOT, Sacci, Jr. JB, Azad AF. Retrieving Parasite Specific Liver Stage Gene Products in Plasmodium yoelii Infected Livers Using Differential Display. Molecular and Biochemical Parasitology (Nov., 2000) 111:143-151.

7. Lau AOT, Sacci, Jr. JB, Azad AF. Optimization of Plasmodium yoelii Messenger RNA in BALB/c Livers. Journal of Parasitology (Feb., 2001) 87:19-23.

8.Lau AOT, Sacci, Jr., JB, Azad AF. Host Responses to Plasmodium yoelii Hepatic Stages: Paradigm in Host-Parasite Interaction. Journal of Immunology (Feb., 2001) 166:1945-1950.

9. Liston, DR, Lau AOT, Smales ST, Johnson PJ. Initiator Recognition in a Primitive Eukaryote: IBP39, an Initiator Binding Protein from Trichomonas vaginalis. Molecular and Cell Biology (Nov., 2001) 22:7872-7882.

10. Sacci, Jr., JB, Aguiar JO, Lau AOT, Hoffman SL. Laser Capture Microdissection and Molecular Analysis of Plasmodium yoelii Liver-Stage Parasites. Molecular and Biochemical Parasitology (Feb., 2002) 119: 285-289.

11. Lau AOT, Liston DR, Vanacova S, Johnson PJ. Trichomonas vaginalis Initiator Binding Protein, IBP39, Contains a Novel DNA Binding Motif. Molecular and Biochemical Parasitology (2003) 130: 167-171.

12. Schumacher M, Lau AOT, Johnson PJ. Structural Basis of Core Promoter Recognition in a Primitive Eukaryote. Cell (Nov 14, 2003) 115: 413-424.

13. Lau AOT, Smith AJ, Brown, MT, Johnson PJ. Trichomonas vaginalis Initiator Binding Protein (IBP39) and RNA Polymerase II Large Subunit Carboxy Terminal Domain Interaction. (in press in Molecular and Biochemical Parasitology)

14. Lau AOT, Roalson EH, Brayton KA, Nene VM, Knowles DP, McElwain TF. Green not Red! Phylogenetic position of the Apicomplexan plastid. (manuscript in review in Molecular and Phylogenetic Evolution)

15. Lau AOT, Tibbals DL and McElwain TF. Development of a Babesia bovis microarray for analysis of gene expression. (manuscript in review in Molecular and Biochemical Parasitology)

16. Nene VM, Brayton KA, Lau AOT et al. Genome sequence of Babesia bovis. (manuscript in preparation)

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