Faculty
840D Russell Laboratories
1630 Linden Drive
Madison, WI 53706
- B.S. Microbiology, Wuhan University
- M.S. Biology, Brock University
- Ph.D. Entomology, University of Minnesota
- Post Doctorate Training, Developmental Biology, University of Washington
Toxicology/Molecular Biology
- Cholesterol intracellular transport in insect models
- Insect hormone-regulated stage-specific gene expression
- Sterol carrier protein- inhibitors: insect growth regulator/mode of action
Metamorphosis is a very complex process in insects. Cross-talk between Juvenile hormone and ecdysteroids initiates metamorphosis in the last larval stadium and in pupal/adult development. I am interested in hormone-regulated gene expression during metamorphosis in insects. The model systems used in my laboratory are the Yellow fever mosquito, Aedes aegypti and the tobacco hornworm, Manduca sexta.
The precursor for ecdysteroid biosynthesis is cholesterol, which has to be obtained from exogenous sources in insects because there is no de novo cholesterol biosynthesis. Insects are efficient in converting phytosterols to cholesterol. However, one of the key processes of absorbing cholesterol or sterols is intracellular transportation of cholesterol/sterols through the midgut. My interest in cholesterol metabolisms is focused on intracellular cholesterol trafficking and how this process is controlled in insects.
ENT 321: Physiology of Insects
ENT 632: Ecotoxicology: The chemical players
Molecular and Environmental Toxicology Program
Cellular and Molecular Parasitology Training Program
Recent publications (past 10 years)
2012
Anstrom DM, Zhou X, Kalk CN, Song B, Lan Q. 2012. Mosquitocidal properties of natural product compounds isolated from Chinese herbs and synthetic analogs of curcumin. J. Med. Entomol. 49(2):350-5.
Xin D, Ma H, Zhang X, Liu K, Peng J, Lan Q, Hong H. 2012. Characterization of the sterol carrier protein-x/sterol carrier protein-2 gene in the cotton bollworm, Helicoverpa armigera. J. Insect Physiol. 58(11):1413-23
Peng R, Fu Q, Schwaegler T, Hong H, Lan Q. 2012. THAP and ATF-2 regulated sterol carrier protein-2 promoter activities in the larval midgut of the yellow fever mosquito Aedes aegypti. PLoS ONE. 7(10): e46948.
2011
Peng R, Maklokova VI, Chandrashekhar JH, Lan Q. 2011. In vivo functional genomic studies of sterol carrier protein-2 gene in the yellow fever mosquito. PLoS ONE. 6(3):e18030
Kim M-S, Lan, Q. 2011. Larvicidal activity of alpha-mangostin in the Colorado potato beetle, Leptinotarsa decemlineata Say. J. Pesticide Science. In press
Fu Q, Lynn-Miller A, Lan Q. 2011. Characterization of the oxysterol-binding protein gene family in the yellow fever mosquito, Aedes aegypti. Insect Mol. Biol. In press
2010
Vyazunova I, Lan Q. 2010. Yellow fever mosquito sterol carrier protein-2 gene structure and transcriptional regulation. Insect Mol. Biol. 19(2):205-215.
Larson RT, Lorch JM, Pridgeon JW, Becnel JJ, Clark GG, Lan Q. 2010. The biological activity of α-mangostin, a larvicidal botanic mosquito sterol carrier protein-2 inhibitor. J. Med. Entomol. 47(2):249-257.
Singarapu KK, Radek JT, Tonelli M, Markley JL, Lan, Q. 2010. Differences in the structure and dynamics of the apo- and palmitate-ligated forms of Aedes aegypti sterol carrier protein 2 (AeSCP-2). J. Biol. Chem. 285(22):17046-17053.
Kim M-S, Lan, Q. 2010. Sterol Carrier Protein-x Gene and Effects of Sterol Carrier Protein-2 Inhibitors on Lipid Uptake in Manduca Sexta. BMC-Physiology. 10:9
Radek JT, Dyer DH, Lan, Q. 2010. Effects of Mutations in Aedes aegypti Sterol Carrier Protein-2 on the Biological Function of the Protein. Biochem. 49(35):7532-41.
2009
Larson RT, Wessely V, Jiang Z, Lan Q. 2008. Larvicidal activity of sterol carrier protein-2 inhibitor in four species of mosquitoes. J. Medical Entomol. 45(3):439-444.
Dyer DH, Vyazunova I, Lorch JM, Forest KT, Lan Q. 2009. Characterization of the yellow fever mosquito sterol carrier protein-2 like 3 gene and ligand-bound protein structure. Mol. Cell. Biochem. 326(1-2):67-77.
Li T, Lan Q, Liu N. 2009. Toxicity of Mosquito Sterol Carrier Protein-2 Inhibitors to the Insecticide Resistant Mosquito Culex quinquefasciatus. J. Med. Entomol. 46(6):1430-1435.
2008
Dyer DH, Wessely V, Forest KT, Lan Q. 2008. 3-D structure/function analysis of sterol carrier protein-2-like2 reveals differences among SCP-2 family members. J Lipid Res. 49(3):644-653.
Tribolium Genome Sequencing Consortium. 2008. The genome of the model beetle and pest Tribolium castaneum. Nature 452:949-955.
Vyazunova I and Lan Q. 2008. Insect sterol carrier protein-2 gene family: structures and functions. Chapter 11. In: Recent Advances in Insect Physiology, Toxicology and Molecular Biology. Nannan Liu (Ed). Research Signpost, Kerala, India.
2007
Vyazunova I, Wessely V, Kim M-s, Lan Q. 2007. Identification of two sterol carrier protein-like genes in the yellow fever mosquito, Aedes aegypti. Insect Mol. Biol. 16(3):305-314.
2006
Kato N, Muller CR, Fuchs JF, Wessely V, Lan Q, Christesen BM. 2006. Regulatory mechanisms of chitin biosynthesis and role of chitin in peritrophic matrix formation in the midgut of adult Aedes aegypti. Insect Biochem. Mol. Biol. 36(1):1-9
2005
Kim M-S, Wessely V, Lan Q. 2005. Identification of mosquito sterol carrier protein-2 inhibitors. J. Lipid Res. 46(4):650-657
Kato N, Mueller CR, Wessely V, Lan Q, Christensen BM. 2005. Aedes aegypti phosphohexomutases and uridine diphosphate-hexose pyrophosphorylases: comparison of primary sequences, substrate specificities and temporal transcription. Insect Mol. Biol. 14(6):615-624
Blitzer EJ, Vyazunova I, Lan Q. 2005. Functional analysis of AeSCP-2 using gene expression knockdown in the yellow fever mosquito, Aedes aegypti. Insect Mol. Biol. 14(3):301-307
Kato N, Mueller CR, Wessely V, Lan Q, Christesen BM. 2005. Mosquito glucosamine-6-phosphate N-acetyltransferase: cDNA, gene structure, regulation and enzyme kinetics. Insect Biochem. Mol. Biol. 35(6):637-646
Lan, Q. 2005. Hormone Regulation of Postembryonic Development in Insects. Chapter 6. In: Entomological Research: Progress and Perspectives. Liu, T.-X. and L. Kang (Eds.) Science Press, Beijing.
2004
Vyazunova I, Lan Q. 2004. Stage-specific expression of two actin genes in the Yellow Fever mosquito, Aedes aegypti. Insect Mol. Biol. 13(3):241-249
Lan, Q, Grier, GA. 2004. Critical period for pupal commitment in the Yellow Fever mosquito, Aedes aegypti. J. Insect Physiology. 50(7):667-676
Lan Q, Massey RJ. 2004. Subcellular localization of mosquito sterol carrier protein-2 and sterol carrier protein-x. J. Lipid Res. 45(8):1468-1474
Lan Q, Wessely V. 2004. Expression of a sterol carrier protein-x gene in the yellow fever mosquito, Aedes aegypti. Insect Mol. Biol. 13(5):519-529
2003
Krebs KC, Lan Q. 2003. Isolation and Expression of a Sterol Carrier Protein-2 Gene from the Yellow Fever Mosquito, Aedes aegypti. Insect Mol. Biol. 12(1):51-60
Dyer DH, Lovell S, Thoden JB, Holden HM, Rayment I, Lan Q. 2003. The structural determination of an insect sterol carrier protein-2 with a ligand bound C16 fatty acid at 1.35A resolution. J Biol Chem. 278:39085-39091
2002
Krebs KC, Brzoza KL, Lan Q. 2002. Use of subtracted libraries and macroarray to isolate developmentally specific genes from the mosquito, Aedes aegypti. Insect Biochem. Mol. Biol. 32(12):1757-1767
Research
Cholesterol transport in insects
Cholesterol is a highly hydrophobic molecule; therefore, a fundamental challenge to every animal is to translocate cholesterol in a hydrophilic cellular environment. At the molecular level, little is known about how an intracellular sterol carrier protein transports cholesterol to its targeted cellular destination such as the cytoplasmic membrane and mitochondria The inability to synthesize cholesterol de novo makes insects dependent on the efficient transport mechanisms involved in cellular sterol translocation, which highlights the critical physiological process of cholesterolabsorptionandtransport.
We isolated the first insect intracellular sterol carrier protein using subtracted cDNA libraries from the yellow fever mosquito. The important biological role of AeSCP-2 prompted me to search for chemical inhibitors of AeSCP-2. Using the high throughput screening technology, we identified AeSCP-2 chemical inhibitors from 80,000 compound chemical libraries. AeSCP-2 inhibitors represent a new class of insecticides.
JH biosynthesis pathways in mosquitoes
I have determined the critical time point of metamorphic commitment in the last larval stage in mosquito larvae, which pinpoints the window of JHIII biosynthesis regulation. I have isolated the Aedes JH acid methyl transferase (JHAMT) and methyl famesoate epoxidase (MFE) genes, which encode the last two enzymes that may be involved in JH biosynthesis pathways.
Goals for the future
One of my long-term goals is to elucidate fundamental aspects of cholesterol metabolism: delivery of the hydrophobic cholesterol molecule through the hydrophilic cellular matrix and the physiological importance of this process.
Since the discovery of the first insect sterol carrier protein-2 gene, I have isolated and characterized several other intracellular sterol carrier protein (SCP) genes: AeSCP-2-like-l, AeSCP-2-like-2, AeSCP-2-like-3, AeSCP-x, steroidogenic acute regulatory protein (Startl), and oxysterol binding protein related protein (ORP) genes from Ae. aegypti. These offer for the first time the possibility to conduct an organized series of studies on a very important physiological process in insects, one that is vital to their survival, more specifically to membrane interactions and ultimately, hormone biosynthesis. I will develop a research project in the future to study the regulation of JH biosynthesis pathway in mosquitoes. As the steps in the biosynthetic pathway of JH III following the formation of famesyl pyrophosphate including both JHAMT and MFE are highly specific to insects, inhibitors of these two enzymes could be potent insect growth regulators. I will target JHAMT for the development of novel insecticides via high throughput screening.
Teaching
ENT 321:
Physiology of Insects. Even yrs.; (3cr). Anatomy,histology and basic physiology of organ systems in insects.
ENT 632:
Ecotoxicology: the chemicalplayers. (Crosslisted withM&Envtox, Agronomy, WI Ecol) I; Odd yrs.; 1 cr. Introduction to natural and man-made toxins/toxicants, their distribution, transport, and fate in the environment. Lectures, current research presentations, and discussions.
David Anstrom
Research Associate
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Jayadevi Chandrashekhar
Research Associate
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Il Hwan Kim
Graduate Student
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Qiang Fu
Graduate Student
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Rong Peng
Visiting scholar
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David Dyer
Research Specialist
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