User:Dawn M. Wong

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Dr. Dawn M. Wong

Department of Chemistry

Virginia Tech

Blacksburg, Virginia

VA 24061-0212, USA

Email: dawnwong@vt.edu


Current Research at Virginia Tech (VT), from 2006:


I have been working as a postdoctoral associate in Prof. Paul R. Carlier’s lab at Virginia Tech (VT, Chemistry, 02/2006-01/2009), and spent some time in the lab of Prof. Jeff Bloomquist's lab at VT (Neurotoxicology Laboratory, Department of Entomology) as his Research Associate (01/2009-11/2009). I am currently continuing my research in the lab of Prof. Paul R. Carlier (VT, Chemistry, 12/2009 - present). As part of the Foundation of the National Institute of Health (FNIH) funded Grand Challenges in Global Health (GCGH) project, on Novel Strategies for Insect Control (NSIC), an interdisciplinary approach to the development of selective insecticides is employed, using molecular modeling and screening, target site cloning, structure activity analyses, toxicology testing and novel chemical synthetic methods. The main biological target is the enzyme acetylcholinesterase (AChE) of Anopheles gambiae (AgAChE), which is the predominant malaria parasite transmitter of the mosquito family. In addition to synthesizing test compounds and student mentoring, I am able to apply my structural knowledge and insight regarding the enzyme AChE, acquired from my time at the Weizmann Institute of Science (WIS, 2000-2003), in the research. My current work, which is funded by a new NIH grant (since April 2009), continues the collaborative malaria work in Prof. Carlier's lab, includes some detailed kinetics studies of potent and selective insecticides and molecular modeling for various sources of AChE.


NIH- and FNIH-Funded Malaria research web link: http://www.files.chem.vt.edu/chem-dept/carlier/malariaresearch.pdf


Past Research at the Weizmann Institute of Science (WIS), 2000-2003:


My interest in biologically related and structural biology related research began at the Weizmann Institute of Science (WIS, 2000-2003), with an initial 6-month collaborative program between the lab of Prof. Paul R. Carlier (who moved to Virginia Tech, USA, in August 2000) and the labs of Prof. Israel Silman (Neurobiology) and Prof. Joel L. Sussman (Structural Biology) at WIS. Research work was achieved primarily through protein crystallization and X-ray crystallography using Torpedo californica AChE (TcAChE) and detailed enzyme kinetics.


Research Interests:


My primary research interest, which began from my time at WIS (see above), is in the structure-function relationship study of the enzyme AChE and related proteins, and anti-cholinesterase agents pertaining to diseases. The eventual aim of my research is towards the development of new therapeutics for the symptomatic treatment of Alzheimer's Disease (AD), or insect-selective pesticides, such as against one of the major mosquito vector of malaria, Anopheles gambiae.


Selected peer-reviewed Publications (* signifies corresponding author; ‡ all authors have made substantial contributions to the work):


1. “NEUROTOXICOLOGY OF bis(n)-TACRINES ON Blattella germanica AND Drosophila melanogaster ACETYLCHOLINESTERASE,” James M. Mutunga, Dhana Raj Boina, Troy D. Anderson, Jeffrey R. Bloomquist*, Paul R. Carlier, Dawn M. Wong, Polo C.-H. Lam, and Maxim M. Totrov, Archives of Insect Biochemistry and Physiology 2013, 83, 180-194. PMID: 23740645 [1]. [2]


2. “Aryl methylcarbamates: potency and selectivity towards wild-type and carbamate-insensitive (G119S) Anopheles gambiae acetylcholinesterase, and toxicity to G3 Strain An. gambiae,” Dawn M. Wong, Jianyong Li, Polo C. H. Lam, Joshua A. Hartsel, James M. Mutunga, Maxim Totrov, Jeffrey R. Bloomquist, and Paul R. Carlier*, Chemico-Biological Interactions 2013, 203, 314-418. PMID: 22989775 [3]. [4]


3. “Select small core structure carbamates exhibit high contact toxicity to “carbamate-resistant” strain malaria mosquitoes, Anopheles gambiae (Akron),” Dawn M. Wong, Jiangyong Li, Qiao-Hong Chen, Qian Han, James M. Mutunga, Ania Wysinski, Troy D. Anderson, Haizhen Ding, Tiffany L. Carpenetti, Astha Verma, Rafique Islam, Sally L. Paulson, Polo C.-H. Lam, Maxim Totrov, Jeffrey R. Bloomquist, and Paul R. Carlier*, PLoS ONE, 2012, 7, e46712. PMID: 23049714 [5]. [6]


4. “Re-engineering aryl methylcarbamates to confer high selectivity for inhibition of Anopheles gambiae versus human acetylcholinesterase,” Joshua A. Hartsel, Dawn M. Wong, James M. Mutunga, Ming Ma, Troy D. Anderson, Ania Wysinski, Rafique Islam, Eric A. Wong, Sally L. Paulson, Jiangyong Li, Polo C. H. Lam, Maxim M. Totrov, Jeffrey R. Bloomquist, and Paul R. Carlier*, Bioorganic & Medicinal Chemistry Letters 2012, 22, 4593-4598. PMID: 22738634 [7]. [8]


5. “Towards a Species-Selective Acetylcholinesterase Inhibitor to Control the Mosquito Vector of Malaria, Anopheles gambiae,” Paul R. Carlier*, Troy D. Anderson, Dawn M. Wong, Danny C. Hsu, Joshua Hartsel, Ming Ma, Eric A. Wong, Ranginee Choudhury, Polo C.-H. Lam, Maxim M. Totrov, and Jeffrey R. Bloomquist, Chemico-Biological Interactions 2008, 175, 368-375. PMID: 18554580 [9]. [10]


6. “Bivalent Ligands Derived from Huperzine A as Acetylcholinesterase Inhibitors,” (review article), Haim Haviv, Dawn M. Wong, Israel Silman and Joel L. Sussman,* Current Topics in Medicinal Chemistry 2007, 7, 375-387. PMID: 17305579 [11]. [12]


7. “Complexes of Alkylene-Linked Tacrine Dimers with Torpedo californica Acetylcholinesterase: Binding of bis(5)-Tacrine produces a Dramatic rearrangement in the Active-Site Gorge,” Edwin H. Rydberg, Boris Brumshtein, Harry M. Greenblatt, Dawn M. Wong, David Shaya, Larry D. Williams, Paul R. Carlier, Yuan-Ping Pang, Israel Silman and Joel L. Sussman,* J. Med. Chem. 2006, 49, 5491-5500. PMID: 16942022 [13]. [14]


8. “Preparation of the chiral amine salts [(η5-C5H5)Ru(PPh3)(CNtBu)(NH2R)]PF6, RNH2 = α-methylbenzylamine, 1-cyclohexylethylamine, and 1-(1-napthyl)ethylamine. X-ray single crystal structures of the diastereomeric salts (SRuRC)- and (RRuRC)-[(η5-C5H5)Ru(PPh3)(CNtBu){NH2CH(Me)(Ph)}]PF6,” Dawn M. Wong and Stephen J. Simpson,* Polyhedron 2006, 25, 2303-2317. [15]


9. “Crystal Packing Mediates Enantioselective Ligand Recognition at the Peripheral Site of Acetylcholinesterase,” Haim Haviv, Dawn M. Wong, Harry M. Greenblatt, Paul R. Carlier, Yuan-Ping Pang, Israel Silman, Joel L. Sussman,* J. Am. Chem. Soc. 2005, 127, 11029-11036. PMID: 16076210 [16]. [17]


10. “Acetylcholinesterase Complexed with Bivalent Ligands Related to Huperzine A: Experimental Evidence for Species-Dependent Protein-Ligand Complementarity,” Dawn M. Wong, Harry M. Greenblatt, Hay Dvir, Paul R. Carlier, Yi-Fan Han, Yuan-Ping Pang, Israel Silman, Joel L. Sussman,* J. Am. Chem. Soc. 2003, 125, 363-373. PMID: 12517147 [18]. [19]


11. “X-ray Structures of TcAChE Complexed with (+)-Huperzine A and (-)-Huperzine B: Structural Evidence for an Active-Site Rearrangement,” H. Dvir, H. L. Jiang, D. M. Wong, M. Harel, M. Chetrit, X. C. He, X. C. Tang, I. Silman, D. L. Bai, J. L. Sussman,* Biochemistry 2002, 41, 10810-10818. PMID: 12196020 [20]. [21]


12. “Catalytic Asymmetric Synthesis of Protected Tryptophan Regioisomers,” Paul R. Carlier,* Polo C.-H. Lam, Dawn M. Wong, Journal of Organic Chemistry 2002, 67, 6256-6259. PMID: 12182675 [22]. [23]


13. “3D Structure of Torpedo californica Acetylcholinesterase Complexed with Huprine X at 2.1 Å Resolution: Kinetic and Molecular Dynamic Correlates,” H. Dvir, D. M. Wong, M. Harel, X. Barril, M. Orozco, F. J. Luque, D. Muñoz-Torrero, P. Camps, T. L. Rosenberry, I. Silman, J. L. Sussman,* Biochemistry 2002, 41, 2970-2981. PMID: 11863435 [24]. [25]


BOOK CHAPTERS: (* Designates corresponding author):


1. “Inhibition of Blatella germanica Acetylcholinesterase by Bis(n)-Tacrines: Prospects for the Molecular Design of a Selective Insecticide for a Household Pest.” In Household, Structural and Residential Pest Management. James M. Mutunga, Troy D. Anderson, Dawn M. Wong, Paul R. Carlier, and Jeffrey R. Bloomquist*, ACS Symposium Series, C. J. Peterson and D. M. Stout II, Eds. American Chemical Society: Chicago, IL, 2010, Vol. 1015, Ch. 4, pp. 41-51 (Web publication date: December 20, 2009). [26]


2. “Pharmacological Mapping of the Acetylcholinesterase Catalytic Gorge in Mosquitoes with Bis(n)-Tacrines.” In Advances in Human Vector Control. Troy D. Anderson, Sally L. Paulson, Dawn M. Wong, Paul R. Carlier, and Jeffrey R. Bloomquist*, ACS Symposium Series, J. M. Clark, J. R. Bloomquist, and H. Kawada, Eds. American Chemical Society: Chicago, IL, 2009, Vol. 1014, Ch. 10, pp. 143-151. [27]


PROTEIN DATABANK DEPOSITIONS:


1. PDB ID 1h22 [28] STRUCTURE OF ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH (S,S)-(-)-BIS(10)-HUPYRIDONE AT 2.15 Å RESOLUTION. PMID: 12517147 [29]. [30]

2. PDB ID 1h23 [31] STRUCTURE OF ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH (S,S)-(-)-BIS(12)-HUPYRIDONE AT 2.15 Å RESOLUTION. PMID: 12517147 [32]. [33]

3. PDB ID 1zgb [34] Crystal Structure of Torpedo Californica Acetylcholinesterase in Complex With an (R)-Tacrine(10)-Hupyridone Inhibitor. PMID: 16076210 [35]. [36]

4. PDB ID 1zgc [37] Crystal Structure of Torpedo Californica Acetylcholinesterase in Complex With an (RS)-Tacrine(10)-Hupyridone Inhibitor. PMID: 16076210 [38]. [39]

5. PDB ID 1odc [40] STRUCTURE OF ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH N-4'-QUINOLYL-N'-9"-(1",2",3",4" -TETRAHYDROACRIDINYL)-1,8-DIAMINOOCTANE AT 2.2 Å RESOLUTION. PMID: 16942022 [41]. [42]

6. PDB ID 1ut6 [43] STRUCTURE OF ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH N-9-(1',2',3',4'-TETRAHYDROACRIDINYL)-1,8-DIAMINOOCTANE AT 2.4 ANGSTROMS RESOLUTION. PMID: 16942022 [44]. [45]

7. PDB ID 2ckm [46] TORPEDO CALIFORNICA ACETYLCHOLINESTERASE COMPLEXED WITH ALKYLENE-LINKED BIS-TACRINE DIMER (7 CARBON LINKER). PMID: 16942022 [47]. [48]

8. PDB ID 2cmf [49] TORPEDO CALIFORNICA ACETYLCHOLINESTERASE COMPLEXED WITH ALKYLENE-LINKED BIS-TACRINE DIMER (5 CARBON LINKER). PMID: 16942022 [50]. [51]


Page last updated on 23rd February 2014 16:36, by Dawn M. Wong.

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