Eliot Spindel, MD, PhD is a professor in the Division of Neuroscience at the Oregon National Primate Research Center and holds joint appointments in the Knight Cancer Center, the Neuroscience Graduate Program and the Department of Behavioral Neuroscience and the Department of Cell, Developmental and Cancer Biology.
Fetal lung, infant lung, mature lung and lung cancer are all direct targets of nicotine because of the high expression of nicotinic receptors in normal, developing and diseased lung. A major focus of the Spindel 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.
The Spindel laboratory is also interested in clinical aspects of lung development in terms of better approaches to clinical care of premature infants. Towards that end, in collaboration with OHSU neonatologists and pediatricians we have developed NHP models of premature infant care and modes of CPAP delivery.
In smokers, nicotine 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.Read more
Areas of interest
- Basic Mechanisms of Lung Development
- Potential effects of smoking during pregnancy on lung development and therapeutic interventions
- Clinical approaches to lung development, prematurity and improved respiratory outcomes
- Epigenetic effects of in utero exposure to smoking
- Nicotine, nicotinic receptors and ly-6 proteins
- Nicotine and lung Cancer
- B.S., Massachusetts Institute of Technology 1974
- Ph.D., Massachusetts Institute of Technology 1980
- M.D., Harvard Medical School, Cambridge 1982
- 1980-1982 Postdoctoral Research Fellow (part-time), Laboratory of Neuroendocrine Regulation, Massachusetts Institute of Technology, Cambridge, MA
- 1982-1984 Postdoctoral Research Fellow, Molecular Endocrinology Lab, MA General Hospital, Boston, MA
Honors and awards
- 1974 Phi Beta Kappa, Massachusetts Institute of Technology,
- 1982 Graduation, cum laude, Harvard Medical School,
- 1982 Dr. Sirgay Sanger Award, Harvard Medical School,
- 1984 American Federation for Clinical Research Award to Trainees in Clinical Research,
Memberships and associations
- 1992-1995 Editorial Board, Molecular Endocrinology,
- 1992-1996 Regular member, Endocrine Study Section (NIH),
- 1997-2005 School of Medicine Research Committee, Oregon Health Sciences University,
- 2007 - 2014 ZRG1 RES-B NIH study section (Lung biology conflict study section)
- 2011 - 2017 Regular member, NIH Cancer Etiology (CE) Study Section
- American Society for Clinical Investigation
- Society for Neuroscience
- American Thoracic Society
McEvoy CT, Schilling D, Clay N, Jackson K, Go M, Spitale P, Bunten C, Leiva M, Gonzales D, Hollister-Smith J, Durand M, Frei B, Buist AS, Peters D, Morris CD, Spindel ER. Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in their Newborn Infants: A Randomized Clinical Trial. JAMA (2014), 311:2074-2082. PMCID: PMC4296045
Shorey-Kendrick LE, Ford MM, Allen DC, Kuryatov A, Lindstrom J, Wilhelm L, Grant KA and Spindel ER. Nicotinic receptors in non-human primates: analysis of genetic and functional conservation with humans. Neuropharmacology (2015) 96(Pt B):263-73. PMID: 25661700.
Spindel ER, McEvoy CT. The role of nicotine in the effects of maternal smoking during pregnancy on lung development and childhood respiratory disease: implications for dangers of e-cigarettes. Am J Respir Crit Care Med (2016),193:486-94. PM:26756937.
- "Sensitive windows for in utero exposures and asthma development. Layers of complexity." American Journal of Respiratory and Critical Care Medicine In: , Vol. 196, No. 11, 01.12.2017, p. 1362-1364.
- "Vitamin C prevents offspring DNA methylation changes associated with maternal smoking in pregnancy." American Journal of Respiratory and Critical Care Medicine In: , Vol. 196, No. 6, 15.09.2017, p. 745-755.
- "Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) : Rationale, design, and methods of a randomized, controlled trial of vitamin C supplementation in pregnancy for the primary prevention of effects of in utero tobacco smoke exposure on infant lung function and respiratory health." Contemporary Clinical Trials In: , Vol. 58, 01.07.2017, p. 66-77.
- "Developmental toxicity of nicotine : A transdisciplinary synthesis and implications for emerging tobacco products." Neuroscience and Biobehavioral Reviews In: , Vol. 72, 01.01.2017, p. 176-189.
- "Reply." American Journal of Respiratory and Critical Care Medicine In: , Vol. 194, No. 2, 15.07.2016, p. 247-248.
- "Environmental effects on lung morphogenesis and function : Tobacco products, combustion products, and other sources of pollution." Fetal and Neonatal Lung Development: Clinical Correlates and Technologies for the Future. Cambridge University Press, 2016. p. 77-93.
- "Cholinergic targets in lung cancer." Current Pharmaceutical Design In: , Vol. 22, No. 14, 01.04.2016, p. 2152-2159.
- "The role of nicotine in the effects of maternal smoking during pregnancy on lung development and childhood respiratory disease : Implications for dangers of e-cigarettes." American Journal of Respiratory and Critical Care Medicine In: , Vol. 193, No. 5, 01.03.2016, p. 486-494.
- "Pulmonary Effects of Maternal Smoking on the Fetus and Child : Effects on Lung Development, Respiratory Morbidities, and Life Long Lung Health." Paediatric Respiratory Reviews In: , 2016.
- "Whole-genome characterization in pedigreed non-human primates using genotyping-by-sequencing (GBS) and imputation." BMC Genomics In: , Vol. 17, No. 1, 676, 2016.
- "Nicotinic receptors in non-human primates : Analysis of genetic and functional conservation with humans." Neuropharmacology In: , Vol. 96, No. PB, 5737, 27.06.2015, p. 263-273.
- "Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates." American Journal of Obstetrics and Gynecology In: , Vol. 212, No. 3, 01.03.2015.
- "Role of Lynx1 and related Ly6 proteins as modulators of cholinergic signaling in normal and neoplastic bronchial epithelium." International Immunopharmacology In: , Vol. 29, No. 1, 28.02.2015, p. 93-98.
- "Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants : A randomized clinical trial." Obstetrical and Gynecological Survey In: , Vol. 69, No. 9, 2014, p. 523-525.
- "Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants : A randomized clinical trial." JAMA - Journal of the American Medical Association In: , Vol. 311, No. 20, 2014, p. 2074-2082.
- "Choline transporter-like protein 4 (CTL4) links to non-neuronal acetylcholine synthesis." Journal of Neurochemistry In: , Vol. 126, No. 4, 08.2013, p. 451-461.
- "Fetal pulmonary arterial vascular impedance reflects changes in fetal oxygenation at near-term gestation in a nonhuman primate model." Reproductive Sciences In: , Vol. 20, No. 1, 01.2013, p. 33-38.
- "Bombesin Peptides." Handbook of Biologically Active Peptides. Elsevier Inc., 2013. p. 326-330.
- "Prenatal nicotine exposure alters lung function and airway geometry through α7 nicotinic receptors." American Journal of Respiratory Cell and Molecular Biology In: , Vol. 46, No. 5, 05.2012, p. 695-702.
- "Restriction of placental vasculature in a non-human primate : A unique model to study placental plasticity." Placenta In: , Vol. 33, No. 1, 01.2012, p. 73-76.
- "Muscarinic receptor agonists and antagonists : Effects on cancer." Handbook of Experimental Pharmacology. Vol. 208 2012. p. 451-468 (Handbook of Experimental Pharmacology; Vol. 208).
- "The ly-6 protein, lynx1, is an endogenous inhibitor of nicotinic signaling in airway epithelium." American Journal of Physiology - Lung Cellular and Molecular Physiology In: , Vol. 303, No. 8, 2012.
- "Prenatal nicotine exposure in rhesus monkeys compromises development of brainstem and cardiac monoamine pathways involved in perinatal adaptation and sudden infant death syndrome : Amelioration by Vitamin C." Neurotoxicology and Teratology In: , Vol. 33, No. 3, 05.2011, p. 431-434.
- "Prenatal nicotine exposure increases GABA signaling and mucin expression in airway epithelium." American Journal of Respiratory Cell and Molecular Biology In: , Vol. 44, No. 2, 01.02.2011, p. 222-229.
- "Fetal ventricular diastolic filling characteristics in a primate model : The role of fetal heart rate and pulmonary vascular impedance." Reproductive Sciences In: , Vol. 17, No. 8, 08.2010, p. 760-766.
- "Large scale analysis of positional effects of single-base mismatches on microarray gene expression data." BioData Mining In: , Vol. 3, No. 1, 2, 2010.
- "Nicotine activates and up-regulates nicotinic acetylcholine receptors in bronchial epithelial cells." American Journal of Respiratory Cell and Molecular Biology In: , Vol. 41, No. 1, 01.07.2009, p. 93-99.
- "Is nicotine the estrogen of lung cancer?" American Journal of Respiratory and Critical Care Medicine In: , Vol. 179, No. 12, 15.06.2009, p. 1081-1082.
- "Recruitment of GABAA receptors in chemoreceptor pulmonary neuroepithelial bodies by prenatal nicotine exposure in monkey lung." Advances in Experimental Medicine and Biology. Vol. 648 2009. p. 439-445 (Advances in Experimental Medicine and Biology; Vol. 648).
- "Activated cholinergic signaling provides a target in squamous cell lung carcinoma." Cancer Research In: , Vol. 68, No. 12, 15.06.2008, p. 4693-4700.