Eliot Spindel

Every year more than 400,000 Americans die from smoking-induced diseases. Adults are stricken with lung cancer, COPD and heart disease. Infants die from SIDS and children are stricken with asthma.

Smoking during pregnancy is responsible for nearly 10 percent of fetal deaths and 10 percent of infant deaths during the first year of life. Infants whose mothers smoke during pregnancy are born with reduced lung function and are at increased risk for severe respiratory illness and development of childhood asthma. Despite these grim statistics more than 11 percent of women still smoke during pregnancy, which means that 450,000 infants are at risk through no choice of their own. Smoking in adults is equally bad.  The overwhelming majority of cases of lung cancer and COPD (chronic obstructive pulmonary disease) are caused by smoking. 

The Spindel lab focuses on the role of nicotine, nicotinic receptors and muscarinic receptors in lung cancer, lung disease and lung development and how this can be targeted to develop new clinical therapies. 

and his co-workers have discovered that the nicotine in cigarettes is one of the key factors in harming fetal development and also directly stimulate the growth of lung cancer. The Spindel laboratory is now trying to target the actions of nicotine to devise new therapies for lung cancer and new strategies to block the effects of maternal smoking on fetal development.

Airway epithelium synthesizes acetylcholine and expresses nicotinic and muscarinic receptors.  Thus there is a non-neuronal cholinergic signaling loop in airway epithelium which is affected by endogenous ACh and exogenous nicotine.  Both nicotine and ACh stimulate lung growth and one major focus of the lab is cholinergic stimulation of lung cancer growth.  Many lung cancers secrete acetylcholine with acts as an autocrine growth factor for lung cancer.  This cholinergic autocrine loop presents multiple targets to develop new therapies for lung cancer which the lab is actively invstigating.  The importance of nicotinic receptors in lung cancer has drawn increasing attention because of recent genome wide association studies linking nicotinic receptor polymorphisms to lung cancer, COPD, asthma and nicotine addiction.  The lab  is also interested in novel therapies for COPD and asthma that target nicotinic receptors.

The second major focus of the lab is to understand the role of nicotinic receptors in normal lung development and develop therapeuti approaches to block the effects of prenatal nicotine exposure on lung development.  This is being pursued in clinical studies in conjunction with OHSU pediatrics and maternal-fetal medicine, studies in whole animals and by electophysiology of lung cells from normal and transgenic mice.  An interesting new observation from our lab is that airway epithelium synthesizes multiple neurotransmitters that communicate with each other in an almost neuron-like manner.

Eliot Spindel also directs the Primate Center Molecular Biology Core.  Relate to that the lab is also invloved in research in non-human primate genomics.

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 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.

Key Publications

Song P, Sekhon HS, Fu XW, Maier M, Jia Y, Duan J, Proskosil BJ, Gravett C, Lindstrom J, Mark GP, Saha S, and Spindel ER.  (2008) Activated cholinergic signaling provides a target in squamous cell lung carcinoma.  Cancer Research 68:4693-4700. PMID: 8559515.

Fu XW, Lindstrom J, and Spindel ER.  (2009) Nicotine activates and up-regulates nicotinic acetylcholine receptors in bronchial epithelial cells.  Am J Respir Cell Mol Biol  41:93-99. PMID:19097990.

Spindel ER. (2009) Is nicotine the estrogen of lung cancer?  Am J Respir Crit Care Med 179:1081-1082. PMID:19498063.