Dan Kahne is a chemist who is recognized for his work studying the mechanisms of antibiotic killing and resistance. He is particularly known for his studies characterizing the proteins that assemble the outer membrane that protects Gram-negative bacteria. This membrane provides intrinsic resistance to most antibiotics which can kill Gram-positive bacteria. This outer membrane prevents drugs from penetrating into the cell so that they can reach their cellular target. Kahne was born in Boston, MA and grew up in Lexington, MA. He graduated from Cornell University with a degree in art history and chemistry and from
Columbia University in 1986 with a PhD in synthetic organic chemistry. He was a postdoctoral fellow at Columbia and joined the chemistry faculty at Princeton in 1988. He is a member of the American Academy of Arts and Sciences, American Academy of
Microbiology, and the National Academy of Sciences.

Research Interests

Dan Kahne's laboratory is interested in the problem of antibiotic resistance and has studied the mechanism of antibiotic killing of clinically used antibiotics and how bacteria develop resistance to them. Several antibiotics they have examined interfere with
peptidoglycan biosynthesis. This glycopeptide polymer provides an exoskeleton that surrounds all bacteria, preventing them from bursting due to osmotic stress. Some of the best antibiotics interfere with the assembly of this polymer, but many drugs that kill Grampositive bacteria are ineffective to treat Gram-negative bacteria because these organisms contain an additional outer membrane that functions to exclude these toxic molecules. His lab co-discovered the essential protein complexes that assemble this outer membrane. They have purified the components of a seven-protein complex that assembles lipopolysaccharide on the cell surface and a five-protein complex that inserts integral beta barrel proteins into this outer membrane. Using biochemical reconstitution, they have clarified the energetics of outer membrane assembly, explaining how this membrane can be built outside of the cell where there is no obvious energy source. Because the outer membrane is conserved and essential for survival of all Gram-negative bacteria, their studies have identified new targets to develop drugs to treat resistant Gram-negative infections.

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Section 14: Chemistry