Overview

Academic Positions

1986-1988 Assistant Professor, Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China
1994-1996 Research Associate, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
1996-2000 Assistant Laboratory Member, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
1999-2000 Assistant Attending Neuropharmacologist, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
2000-2010 Associate Attending Neuropharmacologist, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
2010-2013 Associate Member, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
2013-2020 Attending Neuropharmacologist, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
2013-2020 Member, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
2020-present Professor, Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ

Education

1978-1982 M.B. (M.D. equivalent) Medicine, Department of Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
1983-1986 M.S. Biochemistry, Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
1988-1993 Ph.D., Department of Physiology & Biophysics, University of Cincinnati, College of Medicine, Cincinnat

Education

PHD, 1993, University of Cincinnati
MD, 1982, Shanghai University of Traditional Chinese Medicine

Curriculum Vitae

View CV

Languages

Chinese

Relevant Publications

Zhang T, Xu J and Pan YX, A truncated six transmembrane splice variant MOR-1G enhances expression of the full-length severn transmembrane mu opioid receptor through heterodimerization. Mol Pharmacol. 98:514-527, 2020

Brown TG, Xu J, Hurd YL and Pan YX. Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self-administering male rats. J Neurosci Res. Doi: 10.1002/jnr.24640, 2020

Pasternak GW, Childers S and Pan YX. Emerging Insights into mu opioid pharmacology. Chapter 5, In Substance Use Disorders: From Etiology to Treatment (Nader MA and Hurd Y, ed), Springer 2019

Xu J, Lu ZG, Narayan A, Le Rouzic VP, Xu M, Hunkele A, Brown TG, Hoefer WF, Rossi GC, Rice R, Martinez-Rivera A, Rajadhyaksha AM, Catergni L, Bassoni DL, Pasternak GW and Pan YX. Alternatively spliced C-termini of mu opioid receptors impact morphine action. J Clin. Invest. 127:1561-1573, 2017

Lu ZG, Xu J, Rossi G, Majumdar S, Pasternak GW and Pan YX. Mediation of opioid analgesia by truncated six transmembrane GPCR. J Clin. Invest. 125:2626-2630, 2015.

Pan YX. Alternative pre-mRNA splicing of mu opioid receptor gene: Molecular mechanisms underlying the complex actions of mu opioids. Chapter 6, In Pain Genetics: Basic to Translational Science, p80-98, (Belfer I and Diatchenko L, ed), John Wiley & Sons, Inc. 2014

Xu J, Lu Z, Xu M, Pan L, Deng Y, Xie X, Liu H, Ding S, Hurd YL, Pasternak GW, Klein RJ, Cartegni L, Zhou W, Pan YX. A Heroin Addiction Severity-Associated Intronic Single Nucleotide Polymorphism Modulates Alternative Pre-mRNA Splicing of the ? Opioid Receptor Gene OPRM1 via hnRNPH Interactions. J Neurosci. 34:11048-11066. 2014

Xu J, Xu M, Brown T, Rossi GC, Hurd YL, Inturrisi CE, Pasternak GW and Pan YX. Stabilization of the mu opioid receptor by truncated single transmembrane splice variants through a chaperon-like action. J. Biol. Chem. 288:21211-21227, 2013

Pasternak GW and Pan YX. Mu opioids and their receptors: Evolution of a concept. Pharmacol Rev. 65:1257-1317, 2013

Majumdar S, Grinnell S, Le Rouzic V, Burgman M, Polikar L, ANsonoff M, Pintar J, Pan YX and Pasternak GW. Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects. Proc.Natl.Acad.Sci.UAS. 108: 19778-19783, 2011

Areas Of Interest

Opioid; opioid receptor; GPCR; alternative splicing; pain; analgesia; opioid tolerance; opioid addiction; respiratory depression; micro-RNA; transcriptome; posttranscriptional modification; proteomics; epigenetics;

Molecular mechanisms of opioid actions

Most clinically used opioid drugs including morphine, fentanyl and oxycodone, as well as drugs of abuse such as heroin, act through mu opioid receptors. Over the past two decades, my laboratory?s research has been focusing on mu opioid receptors towards our main goals to understand molecular and cellular mechanisms of mu opioid actions and to translate our basic research into development of novel opioid analgesics that have potent analgesic actions devoid of side effects.
One of our major findings in the past years is that the single-copy gene encoding mu opioid receptors, OPRM1, undergoes extensive alternative pre-mRNA splicing, generating multiple receptor isoforms or variants. Alternative splicing of OPRM1 is conserved from rodent to human. These OPRM1 isoforms or variants can be categorized into three structurally distinct types: 1) full-length seven transmembrane (TM) carboxyl (C)-terminal variants, 2) truncated 6TM variants excluding the first TM, and 3) truncated single TM variants that contain only the first TM. The results from our group and others indicated that these OPRM1 splice variants play important roles in mediating the complex actions of various mu opioids. Increasing evidence indicated that these splice variants play important roles in mediating the complex opioid actions.
Our research utilizes multidisciplinary in vitro and in vivo approaches, including molecular biology, biochemistry, pharmacology, and behavioral studies, as well as gene targeting animal models. The current research projects include: 1) Investigating the mechanisms underlying alternative splicing of the mu opioid receptor gene (OPRM1) and its relevance to opioid pharmacology; 2) Mapping and characterizing mu agonist-induced receptor-protein interactions that contribute to opioid actions; 3) Determining molecular mechanisms of mu opioid-induced tolerance, respiratory depression and reward; 4) Examining biased signaling at mu opioid receptor splice variants; 5) Defining molecular mechanism of the novel analgesic drugs; and 6) Developing new opioid drugs that potent in treating various types of pain lacking the side effects associated with traditional opiates.