Ashley

Ashley

Which lab are you currently working in?
I am a staff scientist in the Kappe lab.

What are you doing at Seattle Biomedical Research Institute?
I am studying lipid (fat) metabolism in malaria parasites. This is a really exciting and growing field. Lipids are essential for all living cells and we don’t really understand how the malaria parasite obtains the lipids it needs for growth and replication. I am trying to understand at the cellular level why the ability of the parasite to make lipids is essential when the parasite is developing in the liver.

Where did you grow up?
I grew up in Tavistock, Devon, UK. It is a small rural town (15,000 people!) filled with beautiful sheep and dairy cows. And with beautiful weather just like Seattle! It is thirteen miles from Plymouth (the port from which the Mayflower set sail).

Where did you go to college? What did you like about your school?
When I was in high school in England you had to decide at age sixteen if you wanted to pursue a science or a non-science career. During the last two years of high school, your studies would then focus on those subjects needed for entry into university. At that time, I just knew that I loved biology, but I had no idea what sorts of things you could do with a degree in science. After high school, I went to the University of Bath. Bath is a beautiful city and I enjoyed my studies there a great deal. During my university education, I worked in two different labs. The first one was a food lab. We were trying to find enzymes that would digest bone to find easier ways for making gelatin. The second lab was the National Institute for Medical Research in London. There I studied the oncogene N-myc. My undergraduate research at the NIMR was very successful and I was able to get my first publication!

What did you do after you graduated?
I went to Duke University as an exchange post-college student for one year. I studied an autoimmune disease called myasthenia gravis.

Why did you apply to grad school?
I was told at that time, that without a PhD, it would be difficult to progress in my career in science. As I was sure at that point of my life that I wanted to have a research career, I applied for the PhD program. I did my graduate studies at the London School of Hygiene and Tropical Medicine. During my graduate work, I studied the genetic basis of insecticide resistance in mosquitoes. I was the first in the lab to apply molecular techniques to answer the questions we had concerning insecticide resistance and was able to publish thirteen articles in peer reviewed scientific journals16-29.

Why did you come to Seattle Biomedical Research Institute?
I came to Seattle Biomedical Research Institute because I came to realize that I really missed working on neglected diseases like malaria. A million people a year die from malaria through no fault of their own and I wanted to return to this line of research. It was during the time I was away from tropical disease research that I studied lipid metabolism in humans3-15. I decided to link both of my scientific areas of expertise to look at the growing field of lipid metabolism during malaria infection1-2.

What are your hobbies outside of the lab?
Hiking and gardening

From where you are now, what advice would you give to incoming and graduate BioQuest students?
Talk to as many people as possible and ask them what they do. Search for your interests and try to relate these to a potential career. A PhD teaches you how to ask questions, how to think about these questions, how to build hypotheses and how to design experiments to answer these questions. Furthermore, obtaining a PhD is an incredibly rewarding and fun experience.

Publications:

1. Malaria parasite pre-erythrocytic stage infection: gliding and hiding.
2. An efficient strategy for gene targeting and phenotypic assessment in the Plasmodium yoelii rodent malaria model.
3. Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux.
4. ABCA1 mutants reveal an interdependency between lipid export function, apoA-I binding activity, and Janus kinase 2 activation.
5. ATP-Binding cassette cholesterol transporters and cardiovascular disease.
6. ATP-binding cassette transporter A1 expression disrupts raft membrane microdomains through its ATPase-related functions.
7. ABCA1 and ABCG1 or ABCG4 act sequentially to remove cellular cholesterol and generate cholesterol-rich HDL.
8. Janus kinase 2 modulates the lipid-removing but not protein-stabilizing interactions of amphipathic helices with ABCA1.
9. ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins.
10. Janus kinase 2 modulates the apolipoprotein interactions with ABCA1 required for removing cellular cholesterol.
11. Phospholipid transfer protein interacts with and stabilizes ATP-binding cassette transporter A1 and enhances cholesterol efflux from cells.
12. ABCA1 redistributes membrane cholesterol independent of apolipoprotein interactions.
13. ATP-binding cassette transporter A1 mediates cellular secretion of alpha-tocopherol.
14. ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins.
15. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.
16. Isolation and sequence analysis of P450 genes from a pyrethroid resistant colony of the major malaria vector Anopheles funestus.
17. The Anopheles gambiae detoxification chip: a highly specific microarray to study metabolic-based insecticide resistance in malaria vectors.
18. Genetic mapping of genes conferring permethrin resistance in the malaria vector, Anopheles gambiae.
19. Aldehyde oxidase is coamplified with the World's most common Culex mosquito insecticide resistance-associated esterases.
20. Biochemical monitoring of organophosphorus and carbamate insecticide resistance in Aedes aegypti mosquitoes from Trinidad.
21. Amplification of a serine esterase gene is involved in insecticide resistance in Sri Lankan Culex tritaeniorhynchus.
22. Resistance to insecticides in insect vectors of disease: est alpha 3, a novel amplified esterase associated with amplified est beta 1 from insecticide resistant strains of the mosquito Culex quinquesfasciatus.
23. Site-directed mutagenesis of an acetylcholinesterase gene from the yellow fever mosquito Aedes aegypti confers insecticide insensitivity.
24. Co-amplification explains linkage disequilibrium of two mosquito esterase genes in insecticide-resistant Culex quinquefasciatus.
25. Cloning and localization of a glutathione S-transferase class I gene from Anopheles gambiae.
26. Kinetic and molecular differences in the amplified and non-amplified esterases from insecticide-resistant and susceptible Culex quinquefasciatus mosquitoes.
27. Mosquito carboxylesterase Est alpha 2(1) (A2). Cloning and sequence of the full-length cDNA for a major insecticide resistance gene worldwide in the mosquito Culex quinquefasciatus.
28. The independent gene amplification of electrophoretically indistinguishable B esterases from the insecticide-resistant mosquito Culex quinquefasciatus.
29. Comparisons of nucleic acid sequences of esterases from resistant and susceptible strains of Culex quinquefasciatus.