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Tom WandlessAcademic Appointments
Appointment
Organization
Assistant Professor (Research)
Assistant Professor (Research) (By courtesy)
Chemistry
Member
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Honors & Awards
Title
Organization
Date(s)
Sloan Research Fellow
Alfred P. Sloan Foundation
2000
Dreyfus Teacher-Scholar
Dreyfus Foundation
2000
Professional Education
Degree
Awarding Institution
Field of Study
Year of Graduation
Ph.D.
Harvard University
Chemistry
1993
B.S.
Trinity University
Biochemistry
1988
Web Site Links
Research/Lab website:
Wandless Lab Homepage
Research Interests
The overarching goals of our research program lie at the interface of chemistry and biology. Specifically, we focus on the design and synthesis of molecules that allow us to learn about and control specific cellular processes. The underlying basis for our research is an understanding of the factors that govern the strength and specificity of molecular interactions.
For example, we are currently working on a new and general method to use synthetic molecules to regulate protein function. Studies of mammalian development have been revolutionized by our ability to disrupt specific genes using homologous recombination in animals (e.g., knock-out mice). However interpreting the phenotypes of these mice is often difficult due to embryonic lethality or to cellular/molecular compensation for the missing gene during development. By targeting the protein directly rather than its gene, we have developed a general method to regulate the stability (and thus function) of specific proteins using a synthetic molecule. This new technique allows us to rapidly and reversibly eliminate a specific protein either in cell culture or in living mice.
In another area, we have devised a method to improve binding events between proteins and synthetic ligands by borrowing additional surface area from abundant cellular proteins. We use synthetic chemistry to prepare bifunctional molecules that are capable of binding to two different proteins simultaneously. The resulting trimeric complexes possess additional protein-protein interactions that may contribute favorably to the overall stability of the complex. Bifunctional molecules may also be used to diminish the affinity of an organic compound for its protein receptor. We have used this approach to detoxify bifunctional molecules in human cells that are otherwise cytotoxic to microorganisms. In mammalian cells, the bifunctional molecule binds preferentially to a protective cellular protein, thus sequestering the cytotoxic ligand away from its protein target. In bacteria, which lack the protective protein, only the cytotoxic half of the bifunctional molecule binds to its protein target resulting in selective bacterial death.
For example, we are currently working on a new and general method to use synthetic molecules to regulate protein function. Studies of mammalian development have been revolutionized by our ability to disrupt specific genes using homologous recombination in animals (e.g., knock-out mice). However interpreting the phenotypes of these mice is often difficult due to embryonic lethality or to cellular/molecular compensation for the missing gene during development. By targeting the protein directly rather than its gene, we have developed a general method to regulate the stability (and thus function) of specific proteins using a synthetic molecule. This new technique allows us to rapidly and reversibly eliminate a specific protein either in cell culture or in living mice.
In another area, we have devised a method to improve binding events between proteins and synthetic ligands by borrowing additional surface area from abundant cellular proteins. We use synthetic chemistry to prepare bifunctional molecules that are capable of binding to two different proteins simultaneously. The resulting trimeric complexes possess additional protein-protein interactions that may contribute favorably to the overall stability of the complex. Bifunctional molecules may also be used to diminish the affinity of an organic compound for its protein receptor. We have used this approach to detoxify bifunctional molecules in human cells that are otherwise cytotoxic to microorganisms. In mammalian cells, the bifunctional molecule binds preferentially to a protective cellular protein, thus sequestering the cytotoxic ligand away from its protein target. In bacteria, which lack the protective protein, only the cytotoxic half of the bifunctional molecule binds to its protein target resulting in selective bacterial death.
Publications
- Grimley JS, Sawayama AM, Tanaka H, Stohlmeyer MM, Woiwode TF, Wandless TJ "The Enantioselective Synthesis of Phomopsin B." Angew Chem Int Ed Engl 2007; More »
- Banaszynski LA, Chen LC, Maynard-Smith LA, Ooi AG, Wandless TJ "A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules." Cell 2006; 126: 5: 995-1004 More »
- Heo WD, Inoue T, Park WS, Kim ML, Park BO, Wandless TJ, Meyer T "PI(3,4,5)P3 and PI(4,5)P2 Lipids Target Proteins with Polybasic Clusters to the Plasma Membrane." Science 2006; More »
- Inoue T, Heo WD, Grimley JS, Wandless TJ, Meyer T "An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways." Nat Methods 2005; 2: 6: 415-8 More »
- Banaszynski LA, Liu CW, Wandless TJ "Characterization of the FKBP.rapamycin.FRB ternary complex." J Am Chem Soc 2005; 127: 13: 4715-21 More »
21 publications: view full list
