Ole Mortensen, PhD

Associate Professor; Director, Pharmacology & Physiology Graduate Program

Department: Pharmacology & Physiology

Education

PhD in Molecular Biology - Aarhus University, Denmark (1999)

Awards & Honors

New Investigator Award, Drexel University College of Medicine (2016)
Alfred Benzon Foundation Research Fellowship (2000)
Fuhrman Foundation Award (1998)

Ole V. Mortensen, PhD, is an associate professor in the Department of Pharmacology & Physiology at Drexel University College of Medicine. He is director of the Pharmacology & Physiology graduate program.

Research Overview

Visit the Ole Mortensen Lab

Research Interests

Neurotransmitter transporters, drug addiction and affective disorders

Research

The main goals of Dr. Mortensen's research are focused on enhancing our understanding of how drugs of abuse, antidepressants and other small molecules interact with and modulate the function of monoamine transporters, including the serotonin transporter (SERT), the dopamine transporter (DAT), and the norepinephrine transporter (NET).

DAT, NET, and SERT are the primary mechanism for clearance of their respective neurotransmitter from the extracellular space. They are targets of psychostimulants, such as cocaine and amphetamines, and of antidepressants such as SSRIs.

Dr. Mortensen's lab has recently isolated SERT and DAT cDNAs from the human parasite Schistosoma mansoni. The uptake kinetics for serotonin are indistinguishable between human and parasite SERT but the parasite SERT and DAT displays dramatically reduced affinity for amphetamines and several inhibitors including cocaine and SSRIs. These results suggest that subtle structural differences between the parasite and human carrier exist that determine exogenous substrate and inhibitor interactions and these differences, if identified, can be employed as templates to design targets of transporter modulating molecules. The lab is employing structure/function studies, molecular modeling and in silico virtual drug screens to pursue this hypothesis.

In an unrelated project, Dr. Mortensen's lab has demonstrated that the MAP kinase phosphatase 3 (MKP3) modulates DAT surface expression, voltage gated calcium channel expression, and neurotransmitter release. Taken together, this points to a role of MKP3 in controlling neurotransmitter homeostasis. They are investigating how this central regulator of MAP kinase signaling contributes to various disease states of the brain including drug addiction, psychiatric disorders, and neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's.

In the Media

Tennessee scientists have partnered on cutting-edge discoveries in a race against COVID-19
Knoxville News Sentinel (July 14, 2020)

Discovery: ORNL scientists map out structure of critical protein in COVID-19
Oak Ridger (July 14, 2020)

Tennessee scientists' discoveries crucial
Tennessean (July 14, 2020)

Publications

View all of Dr. Mortensen's publications in PubMed

“Cryo-EM structure of the dopamine transporter with a novel atypical non-competitive inhibitor bound to the orthosteric site”
Pedersen CN, Yang F, Ita S, Xu Y, Akunuri R, Trampari S, Neumann CMT, Desdorf LM, Schiøtt B, Salvino JM, Mortensen OV, Nissen P, Shahsavar A
J Neurochem. 2024 Jul 15. doi: 10.1111/jnc.16179. PMID: 39010681 (July 15, 2024)

“Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments”
Nguyen H, Cheng MH, Lee JY, Aggarwal S, Mortensen OV, Bahar I
Curr Res Physiol. 2024 Mar 15;7:100125. doi: 10.1016/j.crphys.2024.100125. eCollection 2024. PMID: 38836245 (March 15, 2024)

“Inactivation of ERK1/2 Signaling in Dopaminergic Neurons by Map Kinase Phosphatase MKP3 Regulates Dopamine Signaling and Motivation for Cocaine”
Bernstein DL, Lewandowski SI, Besada C, Place D, España RA, Mortensen OV
J Neurosci. 2024 Jan 31;44(5):e0727232023. doi: 10.1523/JNEUROSCI.0727-23.2023. PMID: 38296649 (January 31, 2024)

“Discovery and Development of Monoamine Transporter Ligands”
Aggarwal S, Mortensen OV
Adv Neurobiol. 2023;30:101-129. doi: 10.1007/978-3-031-21054-9_4. PMID: 36928847 (March 17, 2023)

“Molecular characterization of the serotonergic transporter from the cestode Echinococcus granulosus: pharmacology and potential role in the nervous system”
Camicia F, Vaca HR, Guarnaschelli I, Koziol U, Mortensen OV, Fontana ACK
Parasitol Res. 2022 May;121(5):1329-1343. doi: 10.1007/s00436-022-07466-y. Epub 2022 Feb 16. PMID: 35169884 (May 2022)

“Allosteric Modulator KM822 Attenuates Behavioral Actions of Amphetamine in Caenorhabditis elegans through Interactions with the Dopamine Transporter DAT-1”
Refai O, Aggarwal S, Cheng MH, Gichi Z, Salvino JM, Bahar I, Blakely RD, Mortensen OV
Mol Pharmacol. 2022 Mar;101(3):123-131. doi: 10.1124/molpharm.121.000400. Epub 2021 Dec 14. PMID: 34906999 (March 2022)

Additional publications...

“Functional Characterization of the Dopaminergic Psychostimulant Sydnocarb as an Allosteric Modulator of the Human Dopamine Transporter”
Aggarwal S, Cheng MH, Salvino JM, Bahar I, Mortensen OV
Biomedicines. 2021 Jun 2;9(6):634. doi: 10.3390/biomedicines9060634. (June 2, 2021)

“Individual differences in dopamine uptake in the dorsomedial striatum prior to cocaine exposure predict motivation for cocaine in male rats”
Shaw JK, Pamela Alonso I, Lewandowski SI, Scott MO, O'Connor BM, Aggarwal S, De Biasi M, Mortensen OV, España RA
Neuropsychopharmacology. 2021 May 5. doi: 10.1038/s41386-021-01009-2. (May 5, 2021)

"Transport rate of EAAT2 is regulated by amino acid located at the interface between the scaffolding and substrate transport domains"
Duffield M, Patel A, Mortensen OV, Schnur D, Gonzalez-Suarez AD, Torres-Salazar D, Fontana ACK
Neurochem Int. doi: 10.1016/j.neuint.2020.104792. (Jul 12, 2020)

"Identification of a Novel Allosteric Modulator of the Human Dopamine Transporter"
Aggarwal S, Liu X, Rice C, Menell P, Clark PJ, Paparoidamis N, Xiao YC, Salvino JM, Fontana ACK, España RA, Kortagere S, Mortensen OV
ACS Chem Neurosci. doi: 10.1021/acschemneuro.9b00262 (Jun 24, 2019)

"Anti-hypertensive mechanisms of cyclic depsipeptide inhibitor ligands for G_q/11 class G proteins"
Matthew M. Meleka, Alethia J. Edwards, Jingsheng Xia, Shelby A. Dahlen, Ipsita Mohanty, Matthew Medcalf, Shaili Aggarwal, Kevin D. Moeller, Ole V. Mortensen, Patrick Osei-Owusu
Pharmacological Research; 141:264-275 (March 2019)

"Selective activation of Dopamine D3 receptors and norepinephrine transporter blockade enhance sustained attention"
Marshall CA, Brodnik ZD, Mortensen OV, Reith MEA, Shumsky JS, Waterhouse BD, España RA, Kortagere S
Neuropharmacology. pii: S0028-3908(19)30002-4. doi:10.1016/j.neuropharm.2019.01.003. [Epub ahead of print] PubMed PMID: 30633928 (Jan 8, 2019)

"Overview of Monoamine Transporters"
Aggarwal S, Mortensen OV
Curr Protoc Pharmacol.;79:12.16.1-12.16.17. doi: 10.1002/cpph.32. Review. PubMed PMID: 29261228; PubMed Central PMCID: PMC5841473 (Dec 20, 2017)

"In Vitro Assays for the Functional Characterization of the Dopamine Transporter (DAT)"
Aggarwal S, Mortensen OV
Curr Protoc Pharmacol.;79:12.17.1-12.17.21. doi: 10.1002/cpph.33. PubMed PMID: 29261226; PubMed Central PMCID: PMC5741089 (Dec 20, 2017)

“Identification of novel allosteric modulators of glutamate transporter EAAT2”
Kortagere S, Mortensen OV, Xia J, Lester W, Fang Y, Srikanth YVV, Salvino JM, Fontana ACK
ACS Chem Neurosci. doi:10.1021/acschemneuro.7b00308 (Nov 15, 2017)

"MAP Kinase Phosphatase 3 (MKP3) Preserves Norepinephrine Transporter Activity by Modulating ERK1/2 Kinase-Mediated Gene Expression"
Mortensen OV, Larsen MB, Amara SG
Front Cell Neurosci.;11:253. doi: 10.3389/fncel.2017.00253 (Aug 22, 2017)

"Designing modulators of monoamine transporters using virtual screening techniques"
Mortensen OV, Kortagere S
Front Pharmacol.;6:223. doi: 10.3389/fphar.2015.00223 (Sep 29, 201)

"Molecular determinants of transport stimulation of EAAT2 are located at interface between the trimerization and substrate transport domains"
Mortensen OV, Liberato JL, Coutinho-Netto J, Dos Santos WF, Fontana AC
J Neurochem. 133(2):199-210. (2015)

"Identification of an allosteric modulator of the serotonin transporter with novel mechanism of action"
Kortagere S, Fontana AC, Rose DR, Mortensen OV
Neuropharmacology. 72:282-90. (2013)

"MKP3 eliminates depolarization-dependent neurotransmitter release through downregulation of L-type calcium channel Cav1.2 expression"
Mortensen OV
Cell Calcium. 53(3):224-30. (2013)

"Dopamine transport by the serotonin transporter: a mechanistically distinct mode of substrate translocation"
Larsen MB, Sonders MS, Mortensen OV, Larson GA, Zahniser NR, Amara SG
J Neurosci 27;31(17):6605-15 (2011)

"A catecholamine transporter from the human parasite Schistosoma mansoni with low affinity for psychostimulants"
Larsen MB, Fontana AC, Magalhães LG, Rodrigues V, and Mortensen OV
Mol Biochem Parasitol. 177(1):35-41 (2011)

"Two allelic isoforms of the serotonin transporter from Schistosoma mansoni display electrogenic transport and high selectivity for serotonin"
Fontana AC, Sonders MS, Pereira-Junior OS, Knight M, Javitch JA, Rodrigues V, Amara SG, Mortensen OV
Eur J Pharmacol, 616(1-3):48-57 (2009)

"Genetic Complementation Screen Identifies a Map Kinase Phosphatase, MKP3, as a Regulator of Dopamine Transporter Trafficking"
Mortensen OV; Larsen MB; Prasad BM; and Amara SG
Mol Biol Cell 19(7):2818-29 (2008)

"Gain of function mutants reveal sites important for the interaction of the atypical inhibitors benztropine and bupropion with monoamine transporters"
Mortensen, OV; and Amara, SG
J Neurochem 98 (5):1531-40 (2006)

Contact Information

ovm23@drexel.edu

Department of Pharmacology & Physiology
245 N. 15th Street
Mail Stop 488
Philadelphia, PA 19102
Phone: 267.359.2613
Fax: 215.762.2299