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Columbia Professor and Pfizer Inc. Sign Research Agreement for Testing Compounds with Possible Links to Alzheimer's Disease

By Loralee Nolletti

David M. Stern

David M. Stern

David M. Stern, G&J Carrus Professor of Surgical Science and Professor of Physiology and Cellular Biophysics at the College of Physicians and Surgeons, and Pfizer Inc., an international research-based pharmaceutical company, have signed a Sponsored Research Agreement for $100,000. This work will be carried out in close collaboration with Shi Du Yan, Assistant Professor of Clinical Pathology and long-term collaborator with Stern. Under the six-month agreement, signed on December 19, 2001, Yan and Stern will test six of Pfizer's compounds in the COS cell lines in order to appraise their effects on the ABAD (amyloid-ß binding alcohol dehydrogenase) protein, an enzyme found in mitochondria, as well as other locations, in most cells. This protein has the capacity to bind amyloid-ß peptide, associated with Alzheimer's disease, and the interaction of amyloid-ß with ABAD is associated with amplified cell stress and toxicity in cell culture assays.

COS cell lines are commonly used in medical research. Yan and Stern, who identified and characterized the ABAD protein and developed significant expertise in elucidating the enzyme's physiological role, genetically engineered two COS cell lines with extra copies of the ABAD protein. The engineered cell lines over-express the protein wtABAD, a wild-type ABAD, and wtABAD with mutAPP, the wild-type ABAD with a mutated Amyloid Precursor Protein.

Yan and Stern will study the toxicity of the compounds, measuring oxidative stress, and monitoring DNA fragmentation. They will also perform experiments with primary cortical neurons of the central nervous system to better understand the effect of the compounds on authentic neurons and on tumor cells to more readily display any toxic effects of the compounds.

In the research with Pfizer, the Columbia team hopes to gain further insights into the importance of ABAD's function, while the company will gain access to the two genetically altered cell lines to yield toxicity data of the six compounds.

Published: Jan 14, 2002
Last modified: Sep 18, 2002

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