Bruce L. Kagan Laboratory:
[Publications]

Kagan's laboratory uses voltage-clamp techniques in planar lipid bilayer membranes to study the structure and function of channel forming toxins. The major project studies the channels formed by amyloid peptides from Alzheimer's disease, prion disease, diabetes mellitus, other amyloidoses, and CAG triplet repeat diseases such as Huntington's. A second project examines the channels formed by host defense peptides such as defensins and protegrins with the long-term goal of designing more potent antibiotics.

Recently discovered by Kagan's laboratory is that several different amyloid peptides related to Alzheimer's disease, prion related diseases, diabetes mellitus, and reactive amyloidoses can form ion channels in membranes. Kagan has proposed that these channels play a pathogenic role in these illnesses by placing a metabolic strain on the target cells. Kagan's laboratory also demonstrated that the Alzheimer amyloid can inhibit long term potentiation (LTP) in the hippocampus, suggesting that these peptides can cause dysfunction even in the absence of toxicity. It was also shown that inhibition of LTP is correlated with channel forming ability. In addition, Kagan's laboratory recently demonstrated that B-2-microglobulin, serum amyloid A, and polyglutamine can form channels. Currently, Kagan is searching for other channel forming amyloid peptides and seeking inhibitors of channel formation that might be useful as therapeutic agents.

Kagan's laboratory is also studying the properties of antibiotic peptide channel formers called protegrins. These peptides act by channel formation to kill bacteria, fungi, and even enveloped viruses such as HIV. He uses mutant peptides to study structure-function relationships in these peptides as well as designing new versions of these peptides with enhanced channel forming ability and enhanced antibiotic activity as well as decreased toxicity to host cells.

Two clinical projects examine treatments for posttraumatic stress disorder, and the role of S-Adenosylmethionine in psychiatric disorders.

Bruce L. Kagan, M.D., Ph.D.
Professor

Email:
bkagan@mednet.ucla.edu

Phone:
(310)206-7222