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Daniel J. Morgan
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Title Assistant Professor
Institution College of Medicine
Department Anesthesiology
Address 500 University Drive, Hershey, PA 17033
 Mailbox: H187
Telephone 7175310003 x283824
Email
Background
SECONDARY APPOINTMENT:
Pharmacology
Satvir Tevethia Junior Faculty Research Scholar

EDUCATION:
B.A., Grinnell College, 1997
Ph.D., Rutgers University and the University of Medicine and Dentistry of New Jersey, 2004
Postdoctoral Training, University of Washington, 2004-2007
Postdoctoral Training, Indiana University, 2007-2010

NARRATIVE:
The primary focus of my laboratory is to better understand the receptor desensitization mechanisms that are responsible for tolerance to G-protein coupled receptor (GPCR)-directed agonists. In particular, my lab is working to elucidate the biochemical pathways responsible for causing tolerance to cannabinoid drugs such as delta-9-THC. To address this question we have produced mutant mice expressing a desensitization-resistant form of the cannabinoid receptor 1 (CB1). These mutant mice lack putative phosphorylation sites for G-protein coupled receptor kinase (GRK), a kinase that is responsible for mediating desensitization of many GPCRs. This mutation prevents the CB1 receptor from turning itself off when it is continuously exposed to an agonist such as delta-9-THC. Our mutant mice display reduced tolerance when they are given daily injections of delta-9-THC. Recent work from Chavkin and colleagues at the University of Washington has shown that c-Jun N-terminal kinase (JNK) is responsible for mediating acute tolerance to morphine, a ligand for the G-protein coupled mu opioid receptor. Since we find that tolerance is delayed but not prevented in our mutant mice we decided to explore whether JNK might mediate the residual tolerance observed in our mutant mice. We find that tolerance to the analgesic effects of delta-9-THC is completely blocked when we treat mutants with an inhibitor of JNK. This finding identifies a second mechanism of CB1 receptor desensitization that requires JNK signaling and suggests that coordinated action of both GRK and JNK signaling pathways are responsible for tolerance to delta-9-THC. My lab is currently identifying the targets of JNK signaling that are responsible for delta-9-THC tolerance. Since tolerance is a critical limitation to the use of delta-9-THC for the long-term treatment of pain in humans these findings have tremendous clinical importance for the treatment of pain with cannabinoid drugs.
Publications
1. Morgan DJ, Muller CH, Murataeva NA, Davis BJ, Mackie K. ?9-Tetrahydrocannabinol (?9-THC) attenuates mouse sperm motility and male fecundity. Br J Pharmacol. 2012 Apr; 165(8):2575-83.
  View in: PubMed
 
2. Morgan DJ, Day HR, Harris AD, Furuno JP, Perencevich EN. The impact of Contact Isolation on the quality of inpatient hospital care. PLoS One. 2011; 6(7):e22190.
  View in: PubMed
 
3. Atkins N, Mitchell JW, Romanova EV, Morgan DJ, Cominski TP, Ecker JL, Pintar JE, Sweedler JV, Gillette MU. Circadian integration of glutamatergic signals by little SAAS in novel suprachiasmatic circuits. PLoS One. 2010; 5(9):e12612.
  View in: PubMed
 
4. Morgan DJ, Wei S, Gomes I, Czyzyk T, Mzhavia N, Pan H, Devi LA, Fricker LD, Pintar JE. The propeptide precursor proSAAS is involved in fetal neuropeptide processing and body weight regulation. J Neurochem. 2010 Jun; 113(5):1275-84.
  View in: PubMed
 
5. Morgan DJ, Weisenhaus M, Shum S, Su T, Zheng R, Zhang C, Shokat KM, Hille B, Babcock DF, McKnight GS. Tissue-specific PKA inhibition using a chemical genetic approach and its application to studies on sperm capacitation. Proc Natl Acad Sci U S A. 2008 Dec 30; 105(52):20740-5.
  View in: PubMed
 
6. Morgan DJ, Mzhavia N, Peng B, Pan H, Devi LA, Pintar JE. Embryonic gene expression and pro-protein processing of proSAAS during rodent development. J Neurochem. 2005 Jun; 93(6):1454-62.
  View in: PubMed
 
7. Czyzyk TA, Morgan DJ, Peng B, Zhang J, Karantzas A, Arai M, Pintar JE. Targeted mutagenesis of processing enzymes and regulators: implications for development and physiology. J Neurosci Res. 2003 Nov 1; 74(3):446-55.
  View in: PubMed
 
8. Lei Y, Xin X, Morgan D, Pintar JE, Fricker LD. Identification of mouse CPX-1, a novel member of the metallocarboxypeptidase gene family with highest similarity to CPX-2. DNA Cell Biol. 1999 Feb; 18(2):175-85.
  View in: PubMed
 
9. Schuller AG, King MA, Zhang J, Bolan E, Pan YX, Morgan DJ, Chang A, Czick ME, Unterwald EM, Pasternak GW, Pintar JE. Retention of heroin and morphine-6 beta-glucuronide analgesia in a new line of mice lacking exon 1 of MOR-1. Nat Neurosci. 1999 Feb; 2(2):151-6.
  View in: PubMed
 
 
Keyword
Last Name
Institution
    
 
 
 
Keywords   
Spermatozoa
Nerve Tissue Proteins
Sperm Motility
Tetrahydrocannabinol
Neuropeptides
See all (117) keywords
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