OHSU

Eliot R. Spindel

NEUROSCIENCE MEETS LUNG CANCER AND LUNG DEVELOPMENT

Normal lung and lung cancer synthesize and secrete acetylcholine line, and express both nicotinic and muscarinic receptors.  Multiple GWAS studies have now linked nicotinic receptors to increased risk of lung cancer. The Spindel laboratory focuses on the role of acetylcholine, nicotinic and muscarinic receptors in lung development and lung cancer.  This is highly relevant to human health as most lung disease is caused by smoking and lung cells see levels of nicotine 100-fold higher than most any other cell.

In lung cancer, acetylcholine secreted by lung cancers acts as an autocrine growth factor signaling through both nicotinic and muscarinic receptors and levels of acetylcholine are increased more than 100 fold in squamous cell lung carcinomas.  In smokers, nicotine also directly stimulates lung cancer growth by interacting with nicotinic receptors expressed on lung cancer cells.  The ability of cholinergic signaling to stimulate lung cancer growth suggests multiple targets to develop new lung cancer therapies.  Our lab is actively investigating the potential of nicotinic and muscarinic antagonists to block lung cancer growth as well as characterizing molecular mechanisms by which cholinergic signaling stimulates cancer growth and development.  In particular the alpha 3, alpha 5 and alpha7 nicotinic receptors have been linked to lung cancer growth as has the M3 muscarinic receptor.  Another area of investigation is the role of the nicotinic receptor modulatory proteins such as lynx1 and lynx2 which offer an exciting new approach to blocking nicotinic signaling.

The second major focus of the laboratory is to understand the role of nicotinic receptors in normal lung development and develop therapeutic approaches to block the effects of prenatal nicotine exposure on lung development. This is being pursued in clinical studies in conjunction with the OHSU pediatrics and maternal-fetal medicine departments, in studies in monkeys and transgenic mice and by electrophysiology of lung cells. In a pilot study in conjunction with Cindy McEvoy, MD of the OHSU Pediatrics Department, we have shown that daily supplemental vitamin C given to pregnant women who will not quit smoking helps prevent some of the effects of their smoking on fetal lung development.

Eliot Spindel also directs the Primate Center Molecular Biology Core.  Related to that, the lab is also involved in a variety of non-human primate genomics research.

BIOGRAPHY

 

After receiving a B.S. from MIT, Eliot Spindel earned his M.D. from Harvard Medical School in 1980 and his Ph.D. in neuroendocrine regulation from MIT in 1982. He then went to Massachusetts General Hospital and Brigham and Women's Hospital for four years of postdoctoral research in molecular endocrinology. In 1986, he was appointed an assistant professor of medicine at Harvard Medical School, where he remained until his 1989 appointment to the Oregon National Primate Research Center as a scientist in the Division of Neuroscience and an associate professor of cell and developmental biology and anatomy in the OHSU School of Medicine.  Dr. Spindel was promoted to Senior Scientist and Director of the ONPRC Molecular Biology Core in 1995.   

 

KEY PUBLICATIONS
 

Spindel ER. (2009)  Is nicotine the estrogen of lung cancer? Am J Respir Crit Care Med. 179:1081-1082.

Song P, Sekhon HS, Fu XW, Maier M, Jia Y, Duan J, Proskosil BJ, Gravett C, Lindstrom J, Mark GP, Saha S, Spindel ER.  (2008) Activated cholinergic signaling provides a target in squamous cell lung carcinoma.  Cancer Res. 68:4693-4700.

Wongtrakool C, Wang N, Hyde DM, Roman J, Spindel ER. (2012) Prenatal Nicotine Exposure Alters Lung Function and Airway Geometry Through alppha7 Nicotinic Receptors. Am J Respir Cell Mol Biol. 46:695-702.

Fu XW, Rekow SS, Spindel ER. (2012) The ly-6 protein, lynx1 is an endogenous inhibitor of nicotinic signaling in airway epithelium. Am J Physiol Lung Cell Mol Physiol. 303:L661-8.


See a full listing of Dr. Spindel's publications.