Photo of Eliot Spindel, M.D., Ph.D.

Eliot Spindel M.D., Ph.D.

  • (503) 346-5524
    • Professor Oregon National Primate Research Center
    • Associate Professor of Behavioral Neuroscience School of Medicine
    • Associate Professor of Cell, Developmental and Cancer Biology School of Medicine
    • Member OHSU Knight Cancer Institute School of Medicine
    • Director, ONPRC Molecular Technologies Service Core Oregon National Primate Research Center
    • Program in Molecular and Cellular Biosciences School of Medicine

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 during pregnancy are mediated by nicotine, the Spindel laboratory is also interested in potential harms of e-cigarette use during pregnancy on offspring respiratory health.

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 and are studying the potential beneficial effects of supplementary CPAP in moderatley premature infants.

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.

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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
  • e-cigarettes

Education

  • B.S., Massachusetts Institute of Technology 1974
  • Ph.D., Massachusetts Institute of Technology 1980
  • M.D., Harvard Medical School, Cambridge 1982
  • Fellowship:

    • 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

Publications

Selected publications

  • 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.

Publications

  • "Vitamin C prevents the effects of prenatal nicotine on pulmonary function in newborn monkeys" American Journal of Respiratory and Critical Care Medicine May 1 2005
  • "Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells" Endocrinology May 2004
  • "M3 muscarinic receptor antagonists inhibit small cell lung carcinoma growth and mitogen-activated protein kinase phosphorylation induced by acetylcholine secretion" Journal of Cancer Research April 15 2007
  • "Analysis of the gene and multiple messenger ribonucleic acids (mRNAs) encoding human gastrin-releasing peptide" Molecular Endocrinology March 1987
  • "Formation and degradation of deamido-TRH (pyroglutamyl-histidyl-proline) in rat brain after intraventricular injection of TRH" Brain Research July 20 1981
  • "Neuronal nicotinic acetylcholine receptors" American Journal of Physiology - Renal Fluid and Electrolyte Physiology December 2003
  • "Muscarinic receptor agonists and antagonists"   2012
  • "Maternal nicotine exposure upregulates collagen gene expression in fetal monkey lung" American Journal of Respiratory Cell and Molecular Biology  2002
  • "Erratum" Journal of Biological Chemistry  1990
  • "Locations and molecular forms of gastrin-releasing peptide-like immunoreactive entities in ovine pregnancy" Peptides  1996
  • "Fetal ventricular diastolic filling characteristics in a primate model" Reproductive Sciences August 2010
  • "Effects of caffeine on anterior pituitary and thyroid function in the rat" Journal of Pharmacology and Experimental Therapeutics  1980
  • "Pharmacology and cell biology of the bombesin receptor subtype 4 (BB4- R)" Biochemistry June 1 1999
  • "Bombesin Peptides"   2013
  • "Expression of lynx1 in developing lung and its modulation by prenatal nicotine exposure" Cell and Tissue Research May 2005
  • "Leveraging human genomic information to identify nonhuman primate sequences for expression array development" BMC Genomics November 15 2005
  • "Thyrotropin-releasing hormone (TRH) content of rat striatum" Brain Research July 20 1981
  • "Mammalian bombesin-like peptides" Trends in Neurosciences  1986
  • "Intercenter reliability and validity of the rhesus macaque GeneChip" BMC Genomics  2007
  • "Detection of human probombesin mRNA in neuroendocrine (small cell) carcinoma of the lung. In situ hybridization with cRNA probe" Cancer  1989
  • "Thyroid hormone decreases the stability and the poly(A) tract length of rat thyrotropin β-subunit messenger RNA" Molecular Endocrinology April 1991
  • "Amphibian Bombesin-Like Peptides"   2006
  • "Acetylcholine is synthesized by and acts as an autocrine growth factor for small cell lung carcinoma" Journal of Cancer Research January 1 2003
  • "Prenatal nicotine exposure in rhesus monkeys compromises development of brainstem and cardiac monoamine pathways involved in perinatal adaptation and sudden infant death syndrome" Neurotoxicology and Teratology May 2011
  • "Basic and clinical aspects of non-neuronal acetylcholine" Journal of Pharmacological Sciences  2008
  • "TRH immunoreactivity in rat brain regions, spinal cord and pancreas" Brain Research November 17 1980
  • "Synthesis of acetylcholine by lung cancer" Life Sciences March 28 2003
  • "Prenatal nicotine exposure alters pulmonary function in newborn rhesus monkeys" American Journal of Respiratory and Critical Care Medicine September 15 2001
  • "Recruitment of GABAA receptors in chemoreceptor pulmonary neuroepithelial bodies by prenatal nicotine exposure in monkey lung"   2009
  • "Characterization of neuropeptides by reversed-phase, ion-pair liquid chromatography with post-column detection by radioimmunoassay. Application to thyrotropin-releasing hormone, substance P, and vasopressin" Journal of Chromatography B: Biomedical Sciences and Applications March 13 1981

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