Eliot Spindel, M.D., Ph.D.
Oregon National Primate Research Center
Cell & Developmental Biology
Neuroscience Graduate Program
Program in Molecular & Cellular Biosciences
Summary of Current Research
Neuroscience meets smoking, lung cancer and lung development
Normal lung and lung cancer synthesize and secrete acetylcholine, 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.
A 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 in transgenic mice. Key to understanding the effects of maternal smoking during pregnancy on lung development is understanding the balance between the nicotine addiction that drives continued smoking and the direct effects of nicotine on the developing lung. The epigenetic mechanisms underlying how maternal smoking during pregnancy causes life-long changes in offspring lung function are also being investigated. Because so many of the effects of smoking are mediated by nicotine, the Spindel laboratory is also interested in potential harms of e-cigarettes which are basically electronic nicotine delivery devices.
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 in lung cancer growth.
McEvoy et al. Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in their Newborn Infants: A Randomized Clinical Trial. JAMA (2014), 311:2074-2082. PMID: 24838476
Spindel ER. Muscarinic receptor agonists and antagonists; effects on cancer. Handb Exp Pharmacol (2012) 208:451-468. PMID: 22222710
Wongtrakool C, Wang N, Hyde DM, Roman J, Spindel ER. Prenatal Nicotine Exposure Alters Lung Function and Airway Geometry Through alpha7 Nicotinic Receptors. Am J Respir Cell Mol Biol (2012) 46:695-702. PMID: 22246862.
Fu XW, Rekow SS, Spindel ER. The ly-6 protein, lynx1 is an endogenous inhibitor of nicotinic signaling in airway epithelium. Am J Physiol Lung Cell Mol Physiol (2012) 303:L661-8. PMID: 22923641.
Spindel ER. Is nicotine the estrogen of lung cancer? Am J Respir Crit Care Med 2009; 179:1081-1082.
- M.D., Harvard Medical School, 1980
- Ph.D., Massachusetts Institute of Technology, 1982
Dr. Spindel is available as a mentor for 2014-2015.
Dr. Spindel is available as a mentor for 2015-2016.