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Xiang WANG Office: Cristol Chemistry 156
Office Phone: 303 492 7652
E-mail: Xiang.Wang@colorado.edu
FAX: 303 492 5894
Office Phone: 303 492 7652
E-mail: Xiang.Wang@colorado.edu
FAX: 303 492 5894
Assistant Professor
Ph.D.: Boston University, 2005
HHMI Research Associate: Harvard University and Broad Institute of Harvard and MIT, 2008
Research Overview
Chemical biology is an emerging field that integrates several related disciplines, such as synthetic organic chemistry, biochemistry, molecular and cellular biology. Chemical biologists use small molecules to perturb and understand a range of biological processes including signaling and cognition, differentiation and reprogramming, pathology and the treatment of diseases. Numerous naturally occurring and synthetic small molecules have been demonstrated as powerful probes in biology and as drugs in medicine.Naturally occurring small molecules
Natural products, resulting from millions of years of evolution, are valuable tools for chemical biologists to study biological processes. Many of these molecules and their structural analogs often prove useful in medical applications. Recently, researchers have been using bioassays to direct isolations of natural products with desired biological activities, such as anti-cancer, anti-bacterial, or antiviral activities. These molecules (e.g., lundurines, homoharringtonine, and hirsutellones) often possess complex architectures, which provide countless challenges and opportunities for synthetic organic chemists. We plan to develop novel synthetic methodologies and strategies for practical syntheses of these naturally occurring small molecules. We are also interested in discovering the cellular targets of these molecules, in an effort to understand the underlying mechanisms of their natural existence.Small-molecule epigenetic regulators
Epigenetics is the study of stable and heritable changes in gene expression or cellular phenotype without affecting the underlying DNA sequence of the organism. Epigenetic regulation has been proven to play a critical role in many biological processes, such as gene expression, embryonic development and genomic reprogramming. Our studies in this area focus on chromatin modifications, especially covalent modifications of histone proteins (e.g., methylation, acetylation, phosphorylation) and DNA methylation. These modifications are closely regulated by a series of enzymes, such as histone deacetylases (HDACs), histone lysine demethylases (HKMTs), and DNA methyltransferases (DNMTs). Small molecules inhibiting HDACs or DNMTs have already been proven useful in clinical trials of cancer therapies. We plan to develop specific small-molecule modulators of these enzymes using both mechanism-based rationally designed approach and unbiased screening approach. These molecules should complement genetic tools for the elucidation of the critical roles of chromatin-modifying enzymes in biology.Small molecules discovered from biology-focused screens
As chemical genetics has proved to be a unique and powerful method to study biology, more and more biologists are interested in pursuing this kind of studies. We have established collaborations with biologists in a variety of areas to discover small-molecules probes with novel biological activities using state-of-the-art high-throughput screening technologies. Current efforts in this category include discovering small molecules that- prevent degradation of tumor suppressor proteins;
- improve the efficiency of somatic cell reprogramming;
- disrupt specific transcription factor-mediator interaction;
- interfere with bacterial pathogenesis.
Postdoctoral Positions Available
Requirement: Ph.D. degree and documented expertise in cell and molecular biology or synthetic organic chemistry.Interested candidates should apply by email (xiang.wang@colorado.edu), attaching CV, publication list, and contact info for 3 referees.
Selected Publications
Small-Molecule Reagents for Cellular Pull-down Experiments.Wang, X.; Imber, B. S.; Schreiber, S. L. Bioconjug. Chem. 2008, 19, 585-387. [Most-Accessed Article]
Synthesis of the Tetracyclic Core of the Tetrapetalones via Transannular Oxidative [4+3] Cyclization. Wang, X.; Porco, J. A., Jr. Angew. Chem., Int. Ed. Eng. 2005, 44, 3067-3071; 2006, 45, 6607.
Total Synthesis of the Salicylate Enamide Macrolide Oximidine III: Application of Relay Ring-Closing Metathesis. Wang, X.; Bowman, E. J.; Bowman, B. J.; Porco, J. A., Jr. Angew. Chem., Int. Ed. Eng. 2004, 43, 3601-3605.
Total Synthesis of the Salicylate Enamide Macrolide Oximidine II. Wang, X.; Porco, J. A., Jr. J. Am. Chem. Soc. 2003, 125, 6040-6041.
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