Tom Wandless

Professional Education

Postdoctoral Advisees

Kimberly Bonger, Rishi Rakhit

Graduate & Fellowship Program Affiliations

• Chemical and Systems Biology

Web Site Links

• Wandless Lab Homepage

Industry Relationships

Stanford is committed to ethical and transparent interactions with our industry partners. It is our policy to disclose payments of $5,000 or more, equity valued at $5,000 or more in a publicly traded company, or any equity in a privately held company, to physicians and scientists employed by Stanford University from companies or other commercial entities with which they interact as part of their professional activities. View Full Information

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...

Publications

• Chemical control of protein stability and function in living mice. Banaszynski LA, Sellmyer MA, Contag CH, Wandless TJ, Thorne SH. Nat Med. 2008; 14 (10): 1123-7
• Rapid control of protein level in the apicomplexan Toxoplasma gondii. Herm-Götz A, Agop-Nersesian C, Münter S, Grimley JS, Wandless TJ, Frischknecht F, Meissner M. Nat Methods. 2007; 4 (12): 1003-5
• The enantioselective synthesis of phomopsin B. Grimley JS, Sawayama AM, Tanaka H, Stohlmeyer MM, Woiwode TF, Wandless TJ. Angew Chem Int Ed Engl. 2007; 46 (43): 8157-9
• A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. Banaszynski LA, Chen LC, Maynard-Smith LA, Ooi AG, Wandless TJ. Cell. 2006; 126 (5): 995-1004
• An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways. Inoue T, Heo WD, Grimley JS, Wandless TJ, Meyer T. Nat Methods. 2005; 2 (6): 415-8