The Koh Research Group


Philosophy:  The research within the Koh group focuses on the rational molecular design and synthesis of molecules which can serve to address important biological and biomedical problems.

Our Approach to Research:

 Chemists are unique among scientists in their ability to understand and manipulate molecular structure at atomic resolution.  Over the past decade, efforts in structural biology, molecular biology and genomics have provided us with an unprecedented "chemical" view of biological systems.  These structures provide many new and exciting opportunities for chemists who are capable of understanding this molecular view of life and who can in turn make molecules which uniquely modify or control biomolecular processes.

Working in the Chemistry/Biology Continuum:

The Koh Group has diverse array of capabilities to support our multidisciplinary approach to research.  In addition to a full synthetic laboratory, the Koh group has computational resources for computer-aided molecular design, a full molecular biology lab and a full mammalian cell culture facility.  These resources allow us to design projects at atomic resolution and apply them to biomedical problems at the cellular level. 


Molecular Rescue by Molecular Complementation:

Many human genetic diseases are caused by mutations that alter structure and/or specificity of proteins.  Mutations to the family of nuclear hormone receptors, an important class of ligand-dependent transcriptional regulators are associated with a diverse set of human genetic diseases that include rickets, resistance to thyroid hormone, androgen insensitivity syndrome and anti-androgen resistant prostate cancer.  Many of these mutations cause changes in amino acid residues that directly effect ligand-binding and/or ligand-dependent transactivation function.  By examining the atomic level effects of these mutations on ligand binding, the Koh group demonstrated that rational molecular design could be used to develop molecules that can rescue function to disease-associated mutations.  The Koh group has developed compounds that rescue function to certain mutant receptors associated with rickets, resistance to thyroid hormone, TSH-secreting pituitary adenoma, anti-androgen resistant prostate cancer.

Spatiotemporal Gene Regulation by Light-Activated Transcription:

We were the first group to demonstrate that photo-caged (photo-protected) forms of nuclear receptor agonists can be used to regulate targeted gene expression in an exposure dependent manner.  As many genes only elicit there actions through their three dimensional spatial and temporal patterning, this method can allow one unprecedented  insights in to the function of gene patterning of development and homeostasis.


Bioorganic Chemistry / Chemical Biology

    Molecular Design and Synthesis