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J.Moss

 

Jonathan Moss, M.D., Ph.D.


Jonathan Moss is Professor Emeritus of the Department of Anesthesia and Critical Care at the University of Chicago. Dr. Moss was also Professor of the College and served as Chairman of the Institutional Review Board for over 10 years.

 

Dr. Moss was chosen as Speaker for the 2005 482nd Convocation ceremonies:

[ Video ] (Vimeo)
[ Text ] (Adobe Acrobat PDF format)
Contact Information
Office: O-401
Office Phone: (773) 702-3091
e-mail:jm47@uchicago.edu

After an undergraduate education at Harvard, Dr. Moss received his Ph.D. (Professor Toshio Narahashi, Physiology and Pharmacology) and his M.D. from Duke University. He subsequently trained at the NIH under Nobel Laureate Julius Axelrod and Prof I. J. Kopin, and completed a residency in anesthesiology at Massachusetts General Hospital (Harvard). In 1985, after 10 years on the faculty at Harvard, Dr. Moss was appointed Professor at the University of Chicago. Professor Moss has published more than 100 articles and 40 textbook chapters, predominantly in the area of the pharmacology of anesthetic drugs. He has authored the chapters on "Autonomic Pharmacology" and "Herbal Medications" in Miller's Anesthesia, a well-known standard text in the field, and has given the national refresher course lecture to the American Society of Anesthesiologists (ASA) on adverse reactions to anesthetics five times and on peripheral opiate antagonists five times. He has been a visiting professor at more than 100 major universities worldwide in the past three decades, including an appointment as Distinguished Visiting Professor in Anatomy and Developmental Biology at the University College London, where he studied smooth muscle pharmacology with Professor Geoffrey Burnstock. Professor Moss was honored as the convocation speaker at the University of Chicago in 2005. Dr. Moss has delivered the T.H. Seldon Memorial Lecture at the 2008 IARS Annual Meeting, the State of the Art Lecture at the American Society of Clinical Pharmacology and Therapeutics (2010) (see image below), and the Leroy Vandam Memorial Lecture (Harvard) in 2010. He has given refresher courses at the World Federation of Societies of Anesthesiologists meetings in 2012 and 2016 on peripheral opiate antagonists.24 Professor Moss assumed emeritus status on June 30, 2017.


2010 ASCPT State of the Art Lecture Award being presented to
Prof. Moss by Dr. Shiew-Mei Huang president of ASCPT and Deputy Director CDER-FDA

Professor Moss has served as consultant to several drug companies that have introduced new anesthetics, including opiates and muscle relaxants. A special area of his expertise involves adverse reactions to anesthetic drugs and adjuvants in the perioperative period.1,2 He has published extensively on the effects of anesthetic drugs and agents on smooth muscle (vascular, ureteral and enteric) and on the effect of sex hormones on the cerebral and coronary vessels. His areas of interest include a study of the influence of dietary glycoalkaloids on cholinesterase function,3 studies of herbal medications in the perioperative period, 4-6 and the development of methylnaltrexone (MNTX), a quaternary peripheral opiate antagonist that relieves the peripheral side effects of opiates while preserving analgesia.7-10  Traditional laxative treatments are often ineffective for many chronic pain patients suffering with opioid-induced constipation. Approximately 80% of chronic pain patients with OIC taking laxatives reported difficulties dealing with their constipation symptoms, as documented by a large patient survey (Pain Medicine, 2008). One third of these chronic pain patients stopped or lowered their opioid dose in order to relieve their constipation, resulting in increased pain levels.

MNTX (RELISTOR´┐Ż), given subcutaneously, has been approved for the treatment of opioid induced constipation (OIC) in palliative care patients in more than 50 countries, including the US, EU, Canada, Australia, and several countries in Asia and South America. MNTX is licensed by the University of Chicago to Progenics Pharmaceuticals and currently sub-licensed to Salix Pharmaceuticals for worldwide sales and development (see announcement). Salix Pharmaceuticals was recently acquired by Valeant Pharmaceuticals International, Inc. (see announcement). RELISTOR was recently approved by the FDA and EMA for the treatment of opioid-induced constipation in patients with non-cancer pain. An oral form of Relistor was approved by the FDA on July 19, 2016 (see announcement).

 


 

A recent focus of Professor Moss' research has been the use of MNTX in the ICU and the relationship of the mu opioid receptor and cancer progression (see UC Press Releases 1 and 2) 11-17,20,21,23 and the use of MNTX in intensive care to facilitate nutrition, restore bowel function and reverse the effects of opiates on bacterial sepsis. 18,19,22 The association between MNTX response and increased survival in advanced cancer patients has been recently presented and published 24 (see attachments 1 and 2). These are the first human data demonstrating that opioid antagonists at clinical doses are associated with increased survival in advanced cancer, and are consistent with our preclinical findings. A recent review article documents the development of methylnaltrexone (see attachment 1). On March 15, 2017 Valeant announced it was entering into an exclusive licensing agreement with Glycyx Pharma Ventures Ltd. to develop oncology indications for Relistor (see announcement).

Selected Bibliography

  1. Renz C, Laroche D, Thurn J, Finn H, Lynch J, Thisted R, Moss J: Tryptase levels are not increased during vancomycin-induced anaphylactoid reactions. Anesthesiology, 89:620-5, 1998
  2. Moss J: Allergic to anesthetics. Anesthesiology 99:521-523, 2003
  3. McGehee DS, Krasowski MD, Fung DL, Wilson B, Gronert GA, Moss J: Cholinesterase inhibition by potato glycoalkaloids slows mivacurium metabolism. Anesthesiology 93:510-519, 2000
  4. Ang-Lee, Michael, Moss J, Yuan, C-S: Herbal medicines and perioperative care. JAMA 286: 208-216, 2001
  5. Yuan C-S, Wei G, Dey L, Karrison T, Nahlik L, Maleckar S, Kasza K, Ang-Lee M, Moss J: American ginseng reduces warfarin's effect in healthy subjects: A randomized controlled trial. Ann Int Med 141:23-27, 2004
  6. Moss, Jonathan M.D., Ph.D.; Yuan, Chun-Su M.D., Ph.D.: Herbal Medicines and Perioperative Care; Editorial Views- Anesthesiology. 105(3):441-442, September 2006.
  7. Yuan CS, Foss JF, O'Connor M, Osinski J, Karrison T, Moss J, Roizen MF: Methylnaltrexone reverses chronic opioid-induced constipation: a randomized, controlled trial. JAMA 283:367-72, 2000.
  8. Ho W-Z, Guo C-J, Yuan C-S, Douglas SD, Moss J: Methylnaltrexone antagonizes opioid-mediated enhancement of HIV infection of human blood mononuclear phagocytes. Journal of Pharmacology and Experimental Therapeutics 307:1158-1162, 2003.
  9. Yuan CS, Doshan H, Charney MR, O'Connor M, Karrison T, Maleckar SA, Israel R, Moss J: Tolerability, gut effects, and pharmacokinetics of methylnaltrexone following repeated intravenous administration in humans. J Clin Pharmacol 45:538-546, 2005
  10. Moss J, Rosow CE: Development of peripheral opioid antagonists: New insights into opioid effects. Mayo Clin Proc 83:1116-1130, 2008
  11. Singleton PA, Lingen MW, Fekete MJ, Garcia JGN, Moss J: Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: Role of receptor transactivation. Article- Microvascular Research, Volume 72, Issues 1-2, July-September 2006, Pages 3-11
  12. Singleton PA, Moreno-Vinasco L, Sammani S, Wanderline SL, Moss J, Garcia JGN: Attenuation of vascular permeability by methylnaltrexone: Role of mu opioid receptor, RhoA/ROCK and SIP3 receptor transactivation. Am J Respir Cell Mol Biol 37:222-231, 2007
  13. Singleton PA, Garcia JGN, Moss J: Synergistic effect of methylnaltrexone with 5-fluorouracil (5-FU) and bevacizumab on inhibition of VEGF-induced angiogenesis. Mol Cancer Ther 7:1669-1679, 2008
  14. Singleton PA, Mambetsariev N, Lennon FE, et al: Methylnaltrexone potentiates the anti-angiogenic effects of MTOR inhibitors. J Angiogenesis Res 2:5, 2010
  15. Mathew B, Lennon FE, Siegler JG, et al: Novel role of the mu opioid receptor in lung cancer progression. Anesth Analg 112:558-567, 2011
  16. Lennon FE, Moss J, Singleton P: The mu opioid receptor in cancer progression: Is there a direct effect? Anesthesiology 116:940-945, 2012
  17. Lennon FE, Mirzapoiazova T, Mambetsariev B, Salgia R, Moss J, Singleton P: Overexpression of the mu opioid receptor in human non-small cell lung cancer promotes Akt and mTOR activation, tumor growth, and metastasis. Anesthesiology 116:857-867, 2012
  18. Babrowski T, Holbrook C, Moss J, Gottlieb L, Valuckaite V, Zaborin A, Poroyko V, Liu DC, Zaborina O, Alverdy JC: Pseudomonas aeruginosa virulence expression is directly activated by morphine and is capable of causing lethal gut derived sepsis in mice during chronic morphine administration. Ann Surg 255:386-393, 2012
  19. Sawh SB, Selvaraj IP, Danga A, Cotton AL, Moss J, Patel PB: Use of methylnaltrexone for the treatment of opioid induced constipation in critical care patients. Mayo Clin Proc 87:255-259, 2012
  20. Singleton P, Mirzapoiazova T, Lennon FE, Moss J, Salgia R: The mu opioid receptor promotes opioid and growth factor-induced proliferation, migration and epithelial mesenchymal transition (EMT) in human lung cancer. PLoS ONE 24:e91577, 2014
  21. Singleton P, Mirzapoiazova T, Rifat H, Salgia R, Moss J: Increased Mu Opioid Receptor Expression in Metastatic Lung Cancer. Br J Anaesth 113: Suppl 1:i103-i-108, 2014
  22. Moss J, Patel P: Nutrition in the acute phase of critical illness. N Engl J Med 19:2449, 2014
  23. Singleton PA, Moss, J, Karp DD, Atkins JT, Janku F:  The mu opioid receptor: a new target for cancer therapy?  Cancer. 2015 Aug 15;121(16):2681-8. doi: 10.1002/cncr.29460. Epub 2015 Jun 4.
  24. Janku F, Johnson LK, Karp DD, Atkins JT, Singleton PA, Moss J: Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer. Ann Oncol. 2016 Nov;27(11):2032-2038. Epub 2016 Aug 29.

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