Løland Lab

The Løland lab focuses on structure-function relationships in membrane transporters with focus on the Neurotransmitter:Sodium Symporter (NSS) class of proteins.

Research focus

The Løland lab focuses on structure-function relationships in membrane transporters with focus on the Neurotransmitter:Sodium Symporter (NSS) class of proteins.

We elucidate at atomic level resolution the molecular mechanisms within the proteins that mediate substrate transport. The focus is on identification of specific domainsthat h undergoes conformational changes during substrate binding and translocation. We also map binding sites and binding modes for substrates (e.g. dopamine, serotonin, amphetamine) and inhibitory drugs (e.g. cocaine, antidepressants).

The methods we use to address these issues include advanced biophysics on purified proteins and all aspects of biochemistry and molecular pharmacology on cell systems.

Recent specific examples of our work include:

1) Use of transition metal ion FRET to directly assess conformational changes in NSS proteins. With this method, we made the intriguing finding that potassium plays a hitherto unrecognized central role in the translocation process of NSS proteins.

2) X-ray crystallography and advanced fluorescent-based approaches have identified a novel conformational state in NSS proteins, which represents an unrecognized rate-limiting barrier in the transport mechanism.

3) We have used hydrogen-deuterium exchange mass spectrometry (HDx-MS) to provide detailed information on the global conformational transitions within the entire protein during transport. This revealed that transient unwinding of multiple helical domains plays a role in substrate translocation.

4) Using classical molecular pharmacological assays, we have established that modafinil analogues through their interaction with the dopamine transporter can serve as lead compounds for the development of the first medical treatment for cocaine abuse.

5) In the serotonin transporter, our investigation on substrate and inhibitor binding sites has recently led to the identification of novel high-affinity allosteric inhibitors of the protein.

6) We have assessed substrate binding with solid state NMR. The results settle a long-standing dispute in the field providing evidence for a single substrate-binding site. This goes against current biochemical and pharmacological findings, which suggest two sites.

Key publications

P. Plenge, A.M. Abramyan, G. Sørensen, A. Mørk, P. Weikop, U. Gether, #B. Bang-Andersen, #L. Shi, #C.J. Loland “The mechanism of a novel high-affinity allosteric inhibitor of the serotonin transporter” Nature Communications (2020) 11:1491. doi: 10.1038/s41467-020-15292-y (IF: 11.88)
K. Gotfryd, T. Boesen, J.S. Mortensen, G. Khelashvili, M. Quick, D.S. Terry, J.W. Missel, M.V. LeVine, P. Gourdon, S.C. Blanchard, J.A. Javitch, H. Weinstein, #C.J. Loland, #P. Nissen, #U. Gether “Mechanism of substrate release in neurotransmitter:sodium symporters: the structure of LeuT in an inward-facing occluded conformation” Nature Communications, (2020) 11(1):1005. doi: 10.1038/s41467-020-14735-w. (IF: 11.88)
A.K. Nielsen, I.R. Möller, Y. Wang, S.G.F. Rasmussen, K. Lindorff-Larsen, #K. Rand, #C.J. Loland ”Substrate-Induced Conformational Dynamics of the Dopamine Transporter” Nature Communications (2019), 10(1): 2714, doi: 10.1038/s41467-019-10449-w (IF: 12.35)
I.R. Möller, M. Silvacka, A.K. Nielsen, S.G.F. Rasmussen, U. Gether, #C.J. Loland, #K. Rand “Conformational Dynamics of the Human Serotonin Transporter during Substrate and Drug Binding” Nature Communications (2019), 10(1):1687. doi: 10.1038/s41467-019-09675-z (IF: 12.35)
P.S. Merkle, K. Gotfryd, M.A. Cuendet, K. Leth-Espersen, U. Gether, C.J. Loland, K.D. Rand: Hydrogen-deuterium exchange reveals local unfolding events related to function in the neurotransmitter sodium symporter homolog LeuT. Science Advances (2018), 4(5):eaar6179, doi: 10.1126/sciadv.aar6179 (impact factor: 11.04)
C S. Erlendsson, K. Gotfryd… U. Gether, K. Teilum, C.J. Loland: Direct Assessment of Substrate Binding to the Neurotransmitter:Sodium Symporter LeuT by Solid State NMR. eLife(2017), 6, e19314 (Impact Factor: 8.30)
C.B. Billesbølle, J.S. Mortensen….H.H. Sitte, U. Gether, C.J. Loland: Transition metal ion FRET uncovers K⁺ regulation of a neurotransmitter:sodium symporter. Nature Communications (2016) 7, 12755 (Impact Factor: 11.3)
M.A.B. Larsen, P. Plenge ….K. Strømgaard, B. Bang-Andersen, C.J. Loland: Structure-activity relationship studies of citalopram derivatives: Examining substituents conferring selectivity for the allosteric site in the serotonin transporter. Br J Pharmacol (2016) 173, 925-36 (Impact Factor: 5.26)
M. Ehsan, Y. Du….C.J. Loland, G. Skiniotis, L. Guan, B. Byrne, B.K. Kobilka, P.S. Chae: Highly Branched Pentasaccharide-Bearing Amphiphiles for Membrane Protein Studies. JACS (2016), 138, 3789-96 (Impact Factor: 13.0)
C.J. Loland, M. Mereu…J. L. Katz, G. Tanda, A. H. Newman: R-Modafinil (Armodafinil): A unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol Psychiatry (2012), 72, 405-13 (Impact Factor: 9.25)
P.S. Chae, S.G. Rasmussen…C.J. Loland…B. Byrne, B. Kobilka, S.H. Gellman: Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins. Nature Methods (2010) 7, 1003-8 (IF: 20.7)
T. Beuming, J. Kniazeff, M. … H. Weinstein, U. Gether, and C. J. Loland: The Binding Sites for Cocaine and Dopamine in the Dopamine Transporter are Overlapping. Nature Neuroscience(2008) 11, 780-789 ( Impact Factor: 14.2)

CV - Claus Løland

CV for Claus J. Løland

Department of Neuroscience, University of Copenhagen
Born: May 24, 1971. Married, two children (age 18 and 16).

Education and training

2011-12	Research Management Master Class. 3 days by SIMI Executive
2009	Research Management Course. 9 days. Copenhagen Business School
2005	Education in university teaching and pedagogy (Adjunktpædagogikum)
2000-3	PhD, Graduate School of Neuroscience
1999	MSc in Human Biology

Academic positions

2019-	Professor, Dept. of Neuroscience
2009-19	Associate Professor, Dept. of Neuroscience
2005-8	Assistant Professor, Dept. of Pharmacology
2003-5	Post Doc, University of Copenhagen

Research and management experience

Head of Laboratory for Membrane Protein Dynamics. Strong leadership and project management skills and a solid scientific background. Supporting a dynamic, inspiring and creative research environment for the team members to achieve the highest level of innovation, motivation and engagement in research.

C.J. Løland’s independent research group was founded in 2005, based on generous grants from the Danish Research Council (Ung Eliteforsker Pris) and the Lundbeck Foundation. The average group size (2005-2018) is 10 persons.

Funding
Total personal share: >28 M DKK from 2000-2018, including

2016	Danish Research Council (FP1, 3y)	Dkr. 2,590,000
2015	Danish Research Council (FP1, 3y)	Dkr. 2,590,000
2012	Lundbeck Foundation (3y)	Dkr. 2,000,000
2011	Danish Research Council (Sapere Aude, Research leader, 4y)	Dkr. 6,658,000
2010	Lundbeck Foundation (2y)	Dkr. 1,600,000
2008	Danish Research Council (3y)	Dkr. 1,620,000
2007	Lundbeck Foundation	Dkr. 1,650,000
2005	Danish Research Council (3y, Ung Eliteforsker Pris)	Dkr. 1,680,000

Partnership in Research Centers

2017-21	Lundbeck Foundation Center “Brewing Diterpenoids”
2015-18	BioSynergy, UCPH Excellence Programme for Interdisciplinary Research
2010-15	Lundbeck Foundation Research Center for Biomembranes in Nanomedicine
2009-14	UNIK Research Center “Synthetic Biology”
2008-13	“BioScaRT” Research Center. UCPH Program of Excellence

Academic involvement

2018-	Executive committee, International Transmembrane Transporter Society
2018-	Steering Committee, Integrative Structural Biology at UCPH (ISBUC)
2016-	Educational Council for School of Medical Sciences
2015	Chair of the Board of Studies for Human Biology & Immunology
2015	International Scientific Advisory Board of European Pharmacology (EPHAR)
2012-17	Board member, Danish Society for Pharm, Tox & Med Chem. Head of Pharmacology Section

Review and Editorial activities

2018 Editorial board member for special issue in Neuropharmacology.
Invited ad hoc reviews from:
Grant proposals: Agencie Nationale de la Recherche (F), Institut National du Cancer (F), EMBL node DANDRITE (DK)
Manuscripts from Journals: E.g. Nature, Nature Communications, British Medical Journal, Biological Psychiatry, Scientific Reports, Biological Pharmacology, Journal of Medicinal Chemistry, Journal of Biological Chemistry etc.

Scientific Communication and Activities
Presenter at >30 intl. conferences. Recent invited presentations include:

2018 Gordon Conference “Membrane Transport Proteins” Newry, ME
2017 “The Brain in Flux”, Maintenon, France
2016 European Congress In Pharmacology, Istanbul, Turkey
2016 “Receptor Chemistry: Reality and Vision” Camerino, Italy
2016 Winther Conference on Brain Research, Breckenridge (CO), USA
Organizer of 8 symposia and conferences, examples
2018 Session at ITTS meeting (Vienna)
2014 Scandinavian Physiological Society Symposium, Sigtuna (S)
2013 The 59^th Benzon Symposium: “Membrane Proteins – Structure, Function and Dynamics”

Supervisor for 5 post docs, 7 PhD students, 3 Research assistants, >12 master students.

Outreach
Regular lecturer at Forsknings Døgn and Dansk Naturvidenskabsfestival with focus on the effects of cocaine. Interviewed on TV/Radio (e.g. in DR1 - 21 Søndag, TV2, TV2 NEWS, DR P1) and newspapers (e.g. Berlingske) and on internet media at several occasions.

Selected active collaborations
Prof. Brian Kobilka (Nobel Laureate), Stanford Univ.
Eric Gouaux, HHMI investigator, Vollum Inst, Oregon Health & Science Univ.
Prof. Andrew Kruse, Harvard Medical School
Prof. Jonathan Javitch, Columbia Univ.
Assoc. Prof. Satinder Singh, Yale Univ.
Section Chief Amy Newman, National Institute on Drug Abuse-NIH
Senior Investigator Lei Shi, NIDA-NIH
Prof. Pil Soek Chae, Hanyang Univ. Seul
Prof. Harald Sitte, Medical Univ. of Vienna
Prof. Poul Nissen, Aarhus Univ.
Benny Bang-Andersen, Lundbeck A/S

Publications
Since 1999, 71 publications in peer reviewed journals/books, Including publications in Nature Neuroscience, Nature Communications, eLife, PNAS, JACS (2), Nature Methods, Biological Psychiatry, Science Advances, Chemical Science (3), J. Clinical Investigations, J Neurosci and JBC (10). H-factor: 24. Avg. citations per paper: 32 (source: SCI))

Techniques

In house experimental methods include:

Classical molecular biology (cloning, mutagenesis, expression vectors)
Molecular pharmacology (Radioligand binding and transport assays. Scintillation proximity assay)
Cell culture development (HEK293 cells mono layer and suspension cultures; COS7 cells, E. coli.)
Protein purification (His-/strep-tac immobilization, detergent screens, protein stability tests, nanobodies)
Membrane protein expression platforms (BacMAM, lipofectamine, IPTG etc.)
Biochemistry (Cysteine reactive chemistry, WB, Co-IP, zinc site engineering etc.)
Site-directed fluorescence labeling of purified protein
Protein reconstitution (proteoliposomes, nanodisc technology)
Biophysical approaches (FRET, tmFRET, x-ray crystallization, fluorescence quenching)

Full publication list

Total number of accepted peer reviewed papers: 79
- of which are reviews: 4
Patent applications: 1
Book chapters/Special editor: 6
Number of citations >2800, H-index: 27 (Source: Scopus),
#shared correspondence; IF: Journal impact factor at the year of publication

I. Peer reviewed Publications

I.I Articles

2020:

1. P. Plenge, A.M. Abramyan, G. Sørensen, A. Mørk, P. Weikop, U. Gether, #B. Bang-Andersen, #L. Shi, #C.J. Loland
“The mechanism of a novel high-affinity allosteric inhibitor of the serotonin transporter”
Nature Communications (2020) 11:1491. doi: 10.1038/s41467-020-15292-y
(IF: 11.88)

2. K. Gotfryd, T. Boesen, J.S. Mortensen, G. Khelashvili, M. Quick, D.S. Terry, J.W. Missel, M.V. LeVine, P. Gourdon, S.C. Blanchard, J.A. Javitch, H. Weinstein, #C.J. Loland, #P. Nissen, #U. Gether
“Mechanism of substrate release in neurotransmitter:sodium symporters: the structure of LeuT in an inward-facing occluded conformation”
Nature Communications, (2020) 11(1):1005. doi: 10.1038/s41467-020-14735-w.
(IF: 11.88)

2019:

3. L. Ghani, C.F. Munk, X. Zhang, S. Katsube, Y. Du, C. Cecchetti, W. Huang, H.E. Bae, S. Saouros, M. Ehsan, L. Guan, X. Liu, C.J. Loland, B.K. Kobilka, B. Byrne, P.S. Chae.
“1,3,5-Triazine-Cored Maltoside Amphiphiles for Membrane Protein Extraction and Stabilization”
Journal of the American Chemical Society (2019). doi: 10.1021/jacs.9b07883. (IF: 14.70)

4. R.D. Slack, T.C. Ku, J. Cao, J.B. Giancola, A. Bonifazi, C.J. Loland, A. Gadiano, J. Lam, R. Rais, B.S. Slusher, M. Coggiano , G. Tanda, A.H. Newman.
“Structure-Activity Relationships for a Series of (Bis(4-fluorophenyl)methyl)sulfinyl Alkyl Alicyclic Amines at the Dopamine Transporter: Functionalizing the Terminal Nitrogen Affects Affinity, Selectivity, and Metabolic Stability”
Journal of Medicinal Chemistry (2019). doi: 10.1021/acs.jmedchem.9b01188 (IF: 6.05)

5. A.K. Nielsen, I.R. Möller, Y. Wang, S.G.F. Rasmussen, K. Lindorff-Larsen, #K. Rand, #C.J. Loland
”Substrate-Induced Conformational Dynamics of the Dopamine Transporter”
Nature Communications (2019), 10(1): 2714, doi: 10.1038/s41467-019-10449-w (IF: 12.35)

6. I.R. Möller, M. Silvacka, A.K. Nielsen, S.G.F. Rasmussen, U. Gether, #C.J. Loland, #K. Rand
“Conformational Dynamics of the Human Serotonin Transporter during Substrate and Drug Binding”
Nature Communications (2019), 10(1):1687. doi: 10.1038/s41467-019-09675-z (IF: 12.35)

7. I.R. Möller, M. Silvacka, J. Hausner A.K. Nielsen, S.G.F. Pospíšilová E, Merkle PS, Lišková R, Polák M, Loland CJ, Kádek A, Man P, Rand KD.
“Improving the Sequence Coverage of Integral Membrane Proteins during Hydrogen/Deuterium Exchange Mass Spectrometry Experiments”
Analytical Chemistry (2019), 91(17):10970-10978. doi: 10.1021/acs.analchem.9b00973 (IF: 6.35)

8. A. Sadaf, M. Ramos, J.S. Mortensen, Y. Du, H.E. Bae, C.F. Munk, P. Hariharan, B. Byrne, B.K. Kobilka, C.J. Loland, L. Guan, P:S. Chae
“Conformationally Restricted Monosaccharide-Cored Glycoside Amphiphiles: The Effect of Detergent Headgroup Variation on Membrane Protein Stability”
ACS Chemical Biology (2019), 14(8):1717-1726. doi: 10.1021/acschembio.9b00166 (IF: 4.37)

9. M. Ehsan, Y. Du, J.S. Mortensen, P. Hariharan, Q. Qu, L. Ghani, M. Das, A. Grethen, B. Byrne, G. Skiniotis, S. Keller, C.J. Loland, L. Guan, B.K. Kobilka, P.S. Chae.
“Self-Assembly Behavior and Application of Terphenyl-Cored Trimaltosides for Membrane-Protein Studies: Impact of Detergent Hydrophobic Group Geometry on Protein Stability”
Chemistry – A European Journal (2019), 25(49): 11545-11554. 10.1002/chem.201902468 (IF: 5.16)

10. M. Ehsan, A. Kumar, J.S. Mortensen, Y. Du, P. Hariharan, K.K Kumar, B. Ha, B. Byrne, L. Guan, B.K. Kobilka, C.J. Loland, P.S. Chae
“Self-assembly behaviors of a penta-phenylene maltoside and its application for membrane protein study”
Chemistry – An Asian Journal (2019), doi: 10.1002/asia.201900224 (IF: 3.69)

11. M. Das, Y. Du, J.S. Mortensen, M. Ramos, L. Ghani, H.J. Lee, H.E. Bae, B. Byrne, L. Guan, C.J. Loland, B.K. Kobilka, P.S. Chae
“Trehalose-cored amphiphiles for membrane protein stabilization: importance of the detergent micelle size in GPCR stability”
Organic & Biomolecular Chemistry (2019), 17(12): 1107-1116, doi: 10.1039/c8ob03153c. (IF: 3.49)

2018:

12. H.E. Bae, Y. Du, P. Hariharan, J.S. Mortensen, K.K. Kumar, B. Ha, M. Das, H.S. Lee, C.J. Loland, L. Guan, B.K. Kobilka, P.S. Chae
“Asymmetric maltose neopentyl glycol amphiphiles for membrane protein study: Effect of detergent asymmetricity on protein stability”
Chemical Science (2018), 10(4): 1107-1116. doi: 10.1039/c8sc02560f (IF: 9.06)

13. P.S. Merkle, K. Gotfryd, M.A. Cuendet, K. Leth-Espersen, U. Gether, C.J. Loland, K.D. Rand
“Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT”
Science Advances (2018), 4(5):eaar6179, doi: 10.1126/sciadv.aar6179 (IF: 11.51)

14. H. Hussain, T. Helton, Y. Du, J.S. Mortensen, P. Hariharan, M. Ehsan, B. Byrne, C.J. Loland, B.K. Kobilka, L. Guan, P.S. Chae.
“A comparative study of branched and linear mannitol-based amphiphiles on membrane protein stability”
Analyst (2018) 143(23):5702-5710 doi: 10.1039/c8an01408f (IF: 3.86)

15. M. Das, Y. Du, J.S. Mortensen, P. Hariharan, H.S. Lee, B. Byrne, C.J. Loland, L. Guan, B.K. Kobilka, P.S. Chae,
“Rationally engineered tandem facial amphiphiles for improved membrane protein stabilization efficacy”
ChemBioChem (2018) doi: 10.1002/cbic.201800388 (IF: 2.69)

16. M. Das, Y. Du, J.S. Mortensen, H.E. Bae, B. Byrne, C.J. Loland, B.K. Kobilka, P.S. Chae
“An Engineered Lithocholate-Based Facial Amphiphile Stabilizes Membrane Proteins: Assessing the Impact of Detergent Customizability on Protein Stability”
Chemistry – A European Journal (2018) doi: 10.1002/chem.201801141 (IF: 5.32)

17. P.S. Chae, M. Ehsan, M. Das, V. Stern, Y. Du, J.S. Mortensen, P. Hariharan, B. Byrne, C.J. Loland, B.K. Kobilka, L. Guan
“Steroid-based amphiphiles for membrane protein study: Importance of alkyl spacer for protein stability”
ChemBioChem (2018) doi: 10.1002/cbic.201800106 (IF: 2.85)

18. A. Sadaf, Y. Du, C. Santillan, J.S. Mortensen, I. Molist, A.B.Seven, P. Hariharan, G. Skiniotis, C.J. Loland, B.K. Kobilka, L. Guan, B. Byrne, P.S. Chae
“Dendronic trimaltoside amphiphiles (DTMs) for membrane protein study”
Chemical Science (2018), 8(12): 2489-2498 (IF: 9.14)

19. M. Ehsan, Y. Du, I. Molist, A.B. Seven, P. Hariharan, J.S. Mortensen, L. Ghani, C.J. Loland, G. Skiniotis, L. Guan, B. Byrne, B.K. Kobilka, P.S. Chae
“Vitamin E-based glycoside amphiphiles for membrane protein structural studies.”
Organic & Biomolecular Chemistry, (2018) 16(14):2489-2498 (IF: 3.56)

20. F. Herborg, T.F. Andreassen, F. Berlin, C.J. Loland, U. Gether
“Neuropsychiatric disease-associated genetic variants of the dopamine transporter display heterogeneous molecular phenotypes”
Journal of Biological Chemistry (2018), doi: 10.1074/jbc.RA118.001753 (IF: 4.13)

2017:

21. M-F. Zou, J. Cao, A. Abramyan, T. Kopajtic, C. Zanettini, D. Guthrie, R. Rais, B. Slusher, L. Shi, C.J. Loland, A.H. Newman
“Structure-activity relationship studies on a series of 3α-[bis(4-fluorophenyl)methoxy]tropanes and 3α-[bis(4-fluorophenyl)methylamino]tropanes as novel atypical dopamine transporter (DAT) inhibitors for the treatment of cocaine use disorders”
Journal of Medicinal Chemistry (2017) 60(24):10172-10691 (IF: 6.26)

22. S. Erlendsson, K. Gotfryd, F.H. Larsen, J.S. Mortensen, M-A. Geiger, B-J van Rossum, H. Oschkinat, U. Gether, #K. Teilum, #C.J. Loland
“Direct Assessment of Substrate Binding to the Neurotransmitter:Sodium Symporter LeuT by Solid State NMR”
eLife (2017), doi: 10.7554/eLife.19314 (IF: 8.30)

23. M. Ehsan, L. Ghani, Y. Du, P. Hariharan, J.S. Mortensen, O. Ribeiro, G. Skiniotis, C.J. Loland, L. Guan, B.K. Kobilka, B. Byrne, P.S. Chae
“New penta-saccharide-bearing tripod amphiphiles for membrane protein structure studies”
Analyst (2017) doi: 10.1039/c7an01168g (IF: 3.89)

24. H. Hussain, J.S. Mortensen, Y. Du, C. Santillan, O. Ribeiro, J. Go, P. Hariharan, C.J. Loland, L. Guan, B.K. Kobilka, B. Byrne, P.S. Chae
“Tandem malonate-based glucosides (TMGs) for membrane protein structural studies”
Science Reports (2017) 7(1):3963. doi: 10.1038/ s41598-017-03809-3. (IF: 4.26)

25. M. Das, Y. Du, J.S. Mortensen, O. Ribeiro, P. Hariharan, L. Guan, C.J. Loland, B.K. Kobilka, B. Byrne, P.S. Chae
“Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein study: importance of chirality in the linker region”
Chemical Science (2017) 8(2):1169-1177. doi: 10.1039/c6sc02981g (IF: 9.14)

26. A.M. Abramyan, S. Stolzenberg, Z. Li, C.J. Loland, F. Noé, L. Shi
“The isomeric preference of an atypical dopamine transporter inhibitor contributes to its selection of the transporter conformation”
ACS Chemical Neuroscience (2017) doi: 10.1021/acschemneuro.7b00094 (IF: 4.35)

27. H. Hussain, Y. Du, E. Tikhonova, J.S. Mortensen, O. Ribeiro, C. Santillan, M. Das, C.J. Loland, L. Guan, B.K. Kobilka, B. Byrne, P.S. Chae
“Resorcinarene-based facial glycosides: implication of detergent flexibility on membrane protein stability”
Chemistry – A European Journal (2017) doi:10.1002/chem.201605016 (IF: 5.29)

28. M. Das, Y. Du, O. Ribeiro, P. Hariharan, J. Mortensen, D. Patra, G. Skiniotis, C.J. Loland, L. Guan, B. Kobilka, B. Byrne, P.S. Chae
”Conformationally preorganized diastereomeric norbornane-based maltosides (NBMs) for membrane protein study: Implications of detergent kink for micellar properties”
Journal of the American Chemical Society (2017) doi:10.1021/jacs.6b11997 (IF: 13.0)

29. S. Topiol, B. Bang-Andersen, C. Sanchez, P. Plenge, C.J. Loland, K. Juhl, K. Larsen, P. Bregnedal, K.P. Bøgesø
“X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT”
Bioorganic & Medicinal Chemistry Letters (2017), 27(3):470-478 (IF: 2.49)

2016:

30. C.B. Billesbølle, J.S. Mortensen, A. Sohail, S.G. Schmidt, L. Shi, H.H. Sitte, U. Gether, C.J. Loland
“Transition metal ion FRET uncovers K+ regulation of a neurotransmitter:sodium symporter”
Nature Communications, DOI: 10.1038/NCOMMS12755. (IF: 11.3)

31. K.H. Cho, P. Hariharan, J.S. Mortensen, Y. Du, A.K. Nielsen, B. Byrne, B.K. Kobilka, C.J. Loland, L. Guan, P.S. Chae.
“Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length”
ChemBioChem (2016) 17(24): 2334-2339 (IF: 2.85)

32. J. Cao, R.D. Slack, O.M. Bakare, C. Burzynski, R. Rais, B.S. Slusher, T. Kopajtic, A. Bonifazi, M.P. Ellenberger, H. Yano, Y. He, G.H. Bi, Z.X. Xi, C.J. Loland, A.H. Newman.
“Novel and high affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) analogues as atypical dopamine transporter inhibitors”
Journal of Medicinal Chemistry (2016), 59(23):10676-10691. (IF: 5.59)

33. A. Sohail, K. Jayaraman, S. Venkatesan, K. Gotfryd, M. Daerr, U. Gether, C.J. Loland, K.T. Wanner, M. Freissmuth, H.H. Sitte, W. Sandtner, T. Stockner
“The environment shapes the inner vestibule of LeuT”
PLoS Computational Biology (2016), 12(11):e1005197. doi: 10.1371 (IF: 4.59)

34. K.H. Cho, O. Ribeiro, Y. Du, E. Tikhonova, J.S. Mortensen, K. Markham, P. Hariharan, C.J. Loland, L. Guan, B.K. Kobilka, B. Byrne, P.S. Chae
“Mesitylene-cored glucoside amphiphiles (MGAs) for membrane protein studies: importance of alkyl chain density in detergent efficacy”
Chemistry – A European Journal (2016), 10.1002/chem.201603338 (IF: 5.29)

35. H.E. Bae, J.S. Mortensen, O. Ribeiro, Y. Du, M. Esan, B.K. Kobilka, C.J. Loland, B. Byrne, P.S. Chae
“Tandem Neopentyl Glycol Maltosides (TNMs) for Membrane Protein Stabilisation”
Chemical Communications (2016), 52(84):12104-12107 (IF: 6.57)

36. G. Khelashvili, S.G. Schmidt, L. Shi, J.A. Javitch, U. Gether, C.J. Loland, H. Weinstein.
“Conformational dynamics on the extracellular side of LeuT controlled by Na+ and K+ ions and the protonation state of E290”
Journal of Biological Chemistry (2016), 291(38):19786-99 (IF: 4.26)

37. M. Ehsan, Y. Du, N.J. Scull, E. Tikhonova, J. Tarrasch, J.S. Mortensen, C.J. Loland, G. Skiniotis, L. Guan, B. Byrne, B.K. Kobilka, P.S. Chae.
“Highly Branched Pentasaccharide-Bearing Amphiphiles for Membrane Protein Studies”
Journal of the American Chemical Society (2016), 138(11): 3789-3796 (IF: 13.0)

38. A. Sadaf, J.S. Mortensen, S. Capaldi, E. Tikhonova, P. Hariharan, O. de Castro Ribeiro, C.J. Loland, L. Guan, B. Byrne, P.S. Chae
“A Class of Rigid Linker-bearing Glucosides for Membrane Protein Structural Study”
Chemical Science (2016), 7(3): 1933-1939 (IF: 9.14)

39. H. Hussain, Y. Du, N.J. Scull, J. S. Mortensen, J. Tarrasch, H.E. Bae, C.J. Loland, B. Byrne, B.K. Kobilka, P.S. Chae
“Accessible Mannitol-Based Amphiphiles (MNAs) for Membrane Protein Solubilisation and Stabilisation”
Chemistry – A European Journal (2016), 22(21): 7068-7073 (IF: 5.29)

40. M.A.B. Larsen, P. Plenge, J. Andersen, J.N.N. Eildal, A.S. Kristensen, K.P. Bøgesø, U. Gether, K. Strømgaard, B. Bang-Andersen, C.J. Loland
“Structure-activity relationship studies of citalopram derivatives: Examining substituents conferring selectivity for the allosteric site in the serotonin transporter”
British Journal of Pharmacology (2016), 173(5):925-36 (IF: 5.26)

2015:

41. C.B. Billesbølle, M.B. Krüger, L. Shi, M. Quick, Z. Li, S. Stolzenberg, J. Kniazeff, K. Gotfryd, J.A. Javitch, H. Weinstein, C.J. Loland, U. Gether
“Substrate-induced unlocking of the inner gate determines the catalytic efficiency of a neurotransmitter:sodium symporter”
Journal of Biological Chemistry (2015), 290(44): 26725-26738 (IF: 4.26)

42. V. Jagalski, R. Barker, M.B. Thygesen, K. Gotfryd, M. Krüger, L. Shi, S. Maric, N. Bovet, M. Moulin, M. Haertlein, T. Günther Pomorski, C.J. Loland, M. Cardenas, “Grafted Biomembranes Containing Membrane Proteins - The Case for the Leucine Transporter”
Soft Matter (2015), 11(39): 7707-7711 (IF: 3.80)

43. K.H. Cho, Y. Du, N.J. Scull, P Hariharan. K. Gotfryd, C.J. Loland, L. Guan, B. Byrne, B.K Kobilka, P.S. Chae.
“Novel Xylene-linked Maltose Amphipiles (XMAs) for Membrane Protein Stabilisation”
Chemistry – A European Journal (2015), 21(28): 10008-10013 (IF: 5.29)

44. H.E. Bae, K. Gotfryd, J. Thomas, H. Hussain, M. Ehsan, J. Go, C.J. Loland, B. Byrne, P.S. Chae.
“Deoxycholate-Based Glycosides (DCGs) for Membrane Protein Stabilisation”
ChemBioChem – Communications (2015), 16(10): 1454-1459 (IF: 2.85)

45. S. Stolzenberg, M. Quick, C. Zhao, K. Gotfryd, G. Khelashvili, U. Gether, C.J. Loland, J.A. Javitch, S. Noskov, H. Weinstein, L. Shi.
“Mechanism of the Association between Na+ Binding and Conformations at the Intracellular Gate in Neurotransmitter:Sodium Symporters”
Journal of Biological Chemistry (2015), 290(22): 13992-4003 (IF: 4.26)

46. K.H. Cho, M. Husri, A. Amin, K. Gotfryd, H.J. Lee, J. Go, J.W. Kim, C.J. Loland, L. Guan, B. Byrne, P.S. Chae.
“Maltose neopentyl glycol-3 (MNG-3) analogues for membrane protein study”
Analyst (2015), 140(9): 3157-3163 (IF: 4.03)

47. C.J. Loland.
“The use of LeuT as a model in elucidating binding sites for substrates and inhibitors in neurotransmitter transporters”
Biochimica Biophysica Acta – General Subjects (2015), 1850(3): 500-510 (IF: 3.66)

2014:

48. F.H. Hansen, T. Skjørringe, S. Yasmeen, N. Arends, M.A. Sahai, K. Erreger, T.F. Andreassen, M. Holy, P.J. Hamilton, V. Neergheen, M. Karlsborg, A.H. Newman, S. Pope, S.JR. Heales, L. Friberg, I. Law, L.H. Pinborg, H.H. Sitte, C. J. Loland, L. Shi, H. Weinstein, A. Galli, L.E. Hjermind, L.B. Møller, U. Gether.
“Missense Mutations in the Dopamine Transporter Gene Associated with Adult Parkinsonism and ADHD”
Journal of Clinical Investigation (2014), 124(7): 3107-3120 (IF: 13.2)

49. A.V. Pedersen, T.F. Andreassen, C.J. Loland.
“A Conserved Salt Bridge between Transmembrane Segment 1 and 10 Constitutes an Extracellular Gate in the Dopamine Transporter”
Journal of Biological Chemistry (2014), 289(50): 35003-350014 (IF: 4.57)

50. O.M Okunola-Bakare, J. Cao, T. Kopajtic, J.L. Katz, C.J. Loland, L. Shi, A.H. Newman.
“Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues”
Journal of Medicinal Chemistry (2014), 57(3): 1000-1003 (IF: 5.45)

2013:

51. A.K. Banala, P. Zhang, P. Plenge, G. Cyriac, T. Kopajtic, J.L. Katz, C.J. Loland, A.H. Newman.
“Design and Synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (Citalopram) Analogues as Novel Probes for the Serotonin Transporter S1 and S2 Binding Sites”
Journal of Medicinal Chemistry (2013), 56(23): 9709-9724 (IF: 5.48)

52. P.S. Chae, A.C. Kruse, K. Gotfryd, R.R. Rana, K.H. Cho, S.G. Rasmussen, H.E. Bae R., Chandra, U. Gether, L. Guan, B.K. Kobilka, C.J. Loland, B. Byrne, S.H. Gellman.
“Novel Tripod Amphiphiles for Membrane Protein Analysis”
Chemistry – a European Journal (2013), 56(23): 15645-15651 (IF: 5.70)

53. P.S. Chae, R.R. Rana, K. Gotfryd, S.G.F. Rasmussen, A.C. Kruse, K.H Cho, S. Capaldi, B. Kobilka, C.J. Loland, U. Gether, S. Banerjee, B. Byrne, J.K. Lee, S.H. Gellman
“Glucose-Neopentyl Glycol (GNG) Amphiphiles for Membrane Protein Study”
Chemical Communications (2013), 49(23):2287-2289 (IF: 6.72)

54. P. Zhang, T.N. Jørgensen, C.J. Loland, A.H. Newman
“A Rhodamine-Labeled Citalopram Analogue as a High-Affinity Fluorescent Probe for the Serotonin Transporter”
Bioorganic & Medicinal Chemistry Letters (2013), 23(1):323-326 (IF: 2.33)

55. K.J. Simmons, K. Gotfryd, C.B. Billesbølle, C.J. Loland, U. Gether, C.W. Fishwick, A.P. Johnson
“A virtual high-throughput screening approach to the discovery of novel inhibitors of the bacterial leucine transporter, LeuT”
Molecular Membrane Biology (2013), 30(2):184-194 (IF: 1.73)

2012:

56. P. Plenge, L. Shi, T. Beuming, A.H. Newman, H. Weinstein, U. Gether, C.J. Loland.
“Steric Hindrance mutagenesis in the Conserved Extracellular Vestibule Impedes Allosteric Binding of Antidepressants to the Serotonin Transporter”
Journal of Biological Chemistry (2012), 287(47):39316-39326 (IF: 4.65)

57. C.J. Loland, M. Mereu, O. M. Okunola, J. Cao, T. E. Prisinzano, T. Kopajtic, L. Shi, J. L. Katz, G. Tanda, A. H. Newman
“R-Modafinil (Armodafinil): A unique dopamine uptake inhibitor and potential medication for psychostimulant abuse”
Biological Psychiatry (2012), 72(5):405-413 (IF: 9.25)

58. P.S Chae, S.G. Rasmussen, R.R. Rana, K. Gotfryd, A.C. Kruse, A. Manglik, K.H. Cho, S. Nurva, U. Gether, L. Guan, C.J. Loland, B. Byrne, B.K. Kobilka, S.H. Gellman.
“A New Class of Amphiphiles Bearing Rigid Hydrophobic Groups for Solubilization and Stabilization of Membrane Proteins”
Chemistry (2012), 18(31):9485-9490 (IF: 5.83)

59. G. Sørensen, M. Weikop, D. Dencker, C.J. Loland, C. H. Bengtsen, J. H. Petersen, A. Fink-Jensen, G. Wörtwein, D. P. Woldbye.
“Neuropeptide Y Y5 receptor antagonism attenuates cocaine-induced effects in mice”
Psychopharmacology (Berl) (2012), 222(4):565-577 (IF: 4.06)

2011:

60. A.S. Kristensen, J. Andersen, T.N. Jørgensen, L. Sørensen, J. Eriksen, C.J. Loland, K. Strømgaard, U. Gether.
“The SLC6 neurotransmitter transporters: structure, function and regulation”
Pharmacological Reviews (2011), 63(3):585-640 (IF: 20.2)

61. H. Bisgaard, M.A. Larsen, S. Mazier, T. Beuming, A.H. Newman, H. Weinstein, L. Shi, C.J. Loland, U. Gether.
“The binding sites for benztropines and dopamine in the dopamine transporter overlap”
Neuropharmacology (2011), 60(1):182-190 (IF: 4.81)

2010:

62. P.S. Chae, S.G. Rasmussen, R.R. Rana, K. Gotfryd, R. Chandra, M.A. Goren, A.C. Kruse, S. Nurva, C.J. Loland, Y. Pierre, D. Drew, J.L. Popot, D. Picot, B.G. Fox, L. Guan, U. Gether, B. Byrne, B. Kobilka, S.H. Gellman
“Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins”
Nature Methods (2010), 7(12):1003-1008 (IF: 20.7)

63. P.S. Chae, K. Gotfryd, J. Pacyna, L.J. Miercke, S.G. Rasmussen, R.A. Robbins, R.R. Rana, C.J. Loland, B. Kobilka, R. Stroud, B Byrne, U Gether, S.H. Gellman
“Tandem Facial Amphiphiles for Membrane Protein Stabilization”
Journal of the American Chemical Society (2010), 132(47):16750-16752 (IF: 9.02)

2008:

64. T. Beuming, J. Kniazeff; M.L. Bergmann, L. Shi, L. Gracia, K. Raniszewska, A.H. Newman, J.A. Javitch, H. Weinstein, U. Gether, and C.J. Loland
“The Binding Sites for Cocaine and Dopamine in the Dopamine Transporter are Overlapping”
Nature Neuroscience (2008), 11(7): 780-789 (IF: 14.2)

65. J. Kniazeff, L. Shi, C.J. Loland, H. Weinstein, and U. Gether
“An Intracellular Interaction Network Regulates Conformational Transitions in the Dopamine Transporter”
Journal of Biological Chemistry (2008), 283(25): 17691-17701 (IF: 5.52)

66. C.J. Loland, R.I. Desai, M.-F. Zou, J. Cao, P. Grundt, K. Gerstbrein, H.H. Sitte, A.H. Newman, J.L. Katz, and U. Gether
“Relationship between Conformational Changes in the Dopamine Transporter and Cocaine-Like Subjective Effects of Uptake Inhibitors”
Molecular Pharmacology (2008), 73: 813-823 (IF: 4.71)

2006:

67. K.M. Kahlig, B.J. Lute, Y. Wei, C.J. Loland, U. Gether, J.A. Javitch, A. Galli
“Regulation of Dopamine Transporter Trafficking by Intracellular Amphetamine”
Molecular Pharmacology (2006), 70(2):542-548 (IF: 4.47)

2005:

68. J.H. Cha, M.-F. Zou, E.M. Adkins, S.G.F. Rasmussen, C.J. Loland, B. Shonenberger, U. Gether, and A.H. Newman
“Rhodamine-labeled 2β-carbomethoxy-3β-(3,4-dichlorophenyl)tropane analogues as high-affinity fluorescent probes for the dopamine transporter”
Journal of Medicinal Chemistry (2005), 48(24): 7513-7516 (IF: 4.97)

69. J. Kniazeff, C.J. Loland, N. Goldberg, M. Quick, S. Das, H.H. Sitte, J.A. Javitch, and U. Gether
“Intramolecular Cross-Linking in a Bacterial Homolog of Mammalian SLC6 Neurotransmitter Transporters Suggests an Evolutionary Conserved Role of Transmembrane Segments 7 and 8”
Neuropharmacology (2005), 49(6): 7024-7036 (IF: 3.84)

2004:

70. C. Bjerggaard, J. Fog, H. Hastrup, K. Madsen, C.J. Loland, J. Javitch, and U. Gether
“Surface Targeting of the Dopamine Transporter Involves Discrete Epitopes in the Distal C Terminus but does not Require Canonical PDZ Domain Interactions”
Journal of Neuroscience (2004), 24(31): 7024-7036 (IF: 8.02)

71. C.J. Loland, C. Grånäs, J.A. Javitch, and U. Gether
“Identification of Intracellular Residues in the Dopamine Transporter Critical for Regulation of Transporter Conformation and Cocaine Binding”
Journal of Biological Chemistry (2004), 279(5): 3228-3238 (IF: 6.57)

2003:

72. C.J. Loland, K. Norgaard-Nielsen, and U. Gether
“Probing Dopamine Transporter Structure and Function by Zn2+-site Engineering”
European Journal of Pharmacology (2003), 479(1-3): 187-197 (IF: 2.35)

73. L. Norregaard, C.J. Loland, and U. Gether
“Evidence for distinct sodium, dopamine and cocaine dependent conformational changes in transmembrane segments 7 and 8 of the dopamine transporter”
Journal of Biological Chemistry (2003), 278(33): 30587-30596 (IF: 6.41)

74. C. Grånäs, J. Ferrer, C.J. Loland, J.A. Javitch and U. Gether
“N-terminal Truncation of the Dopamine Transporter Abolishes Phorbol Ester and Substance P Receptor Stimulated Phosphorylation Without Impairing Transporter Internalization”
Journal of Biological Chemistry (2003), 278(7): 4990-5000 (IF: 6.41)

2002:

75. C.J. Loland, L. Norregaard, T. Litman and U. Gether
“Generation of an Activating Zn2+ Switch in the Dopamine Transporter: Mutation of an Intracellular Tyrosine Constitutively Alters the Conformational Equilibrium of the Transport Cycle”
Proceedings of the National Academy of Sciences USA (2002), 99(3): 1683-1688 (IF: 10.7)

2001:

76. N. MacAulay, A. Bendahan, C.J. Loland, T. Zeuthen, B. Kanner and U. Gether
“Engineered Zn2+ Switches in the GABA Transporter-1: Differential Effects on GABA Uptake and Currents”
Journal of Biological Chemistry (2001), 276(44): 40476-40485 (IF: 6.61)

77. U. Gether, L. Norregaard and C.J. Loland
“Delineating Structure-Function Relationships in the Dopamine Transporter from Natural and Engineered Zn2+ Binding Sites”
Life Sciences (2001), 68(19-20):2187-2198 (IF: 1.79)

2000:

78. L. Norregaard, I. Visiers, C.J. Loland, J. Ballasteros, H. Weinstein and U. Gether “Structural Probing of a Microdomain in the Dopamine Transporter by Engineering of Artificial Zn2+ Binding Sites.”
Biochemistry (2000), 39(51): 15836-15846

1999:

79. C.J. Loland, L. Norregaard, and U. Gether
“Defining Proximity Relationships in the Tertiary Structure of the Dopamine Transporter. Identification of a Conserved Glutamic Acid as a Third Coordinate in the Endogenous Zn2+ Binding site”
Journal of Biological Chemistry. (1999), 274(52): 36928-36934 (IF: 7.67)

I.II Book Chapters

80. F.A. Chaudhry, C.J. Loland, A. Ortega, A. Schousboe (Eds)
“Special issue on neurotransmitter transporters”
Neuropharmacology (2019) 161:107859. doi: 10.1016/j.neuropharm.2019.107859

81. J.S. Mortensen, C.J. Loland
“Short-range distances measurement by transition metal ion FRET”
In ‘Biophysics of Membrane Proteins’, (V. Postis & A. Goldman, ed.) Methods in Molecular Biology, Springer Nature, London (2019)

82. C.J. Loland, C. Sanchez, P. Plenge, K.P. Bøgesø, B. Bang-Andersen
“Allosteric Binding in the Serotonin Transporter – Pharmacology, Structure, Function and Potential Use as a Novel Drug Target”
In ‘Allosterism in Drug Discovery’ Royal Society of Chemistry, Drug Discovery Series no. 65 (ed. D. Doller), (2017) page 360-380. doi: 10.1039/9781782629276

83. C.J. Loland and U. Gether
“Neurotransmitter Transporters: Structure, Function and Drug Binding”
in ‘Textbook of Drug Design and Discovery’, 5th edition (ed. U. Madsen), Taylor & Francis Group, LLC, 2015

84. C.J. Loland and U. Gether
“Neurotransmitter Transporters: Structure and Function”
in ‘Textbook of Drug Design and Discovery’, 4th edition (ed.. U. Madsen), Taylor & Francis Group, LLC, 2010

85. C.J. Loland, and U. Gether
“Insights from Endogenous and Engineered Zn2+-binding Sites in Monoamine Transporters”
In Molecular Neuropharmacology: Strategies and Methods (Schousboe, A. and Bräuner-Osborne, H., ed.) Humana Press, Totowa, New Jersey (2004), 191-213

II. Patent applications

“Use of dihydro-isobenzofuran in combination with serotonin reuptake inhibitors for CNS disease e.g. depression, anxiety, bipolar disorder, obsessive compulsory disorder”
Inventors: K.P. Bogeso, K. Juhl, H. Zhong, C.J. Loland
Patent Number: WO2013110313-A1
Patent Assignee Name and Code: LUNDBECK AS H(LUND-C)
Derwent Primary Accession Number: 2013-M11364 [55]

Lab members

Name	Title	Job responsibilities

Andreas Nygaard	PhD Student	Løland Lab
Ciara Frances Pugh	Master-Student	Løland Lab
Claus Juul Løland	Professor	Løland Lab
Ida Hjorslev Poulsen	Research Assistant	Løland Lab
Jeppe Cederholm Nielsen	Master-Student	Løland lab
Kristine Walløe Salomon	Master-Student	Løland Lab
Lone Rosenquist	Laboratory Technician	Løland Lab
Miriam López Navarro	Master-Student	Løland Lab
Per Krener Plenge	Associate Professor Emeritus	Løland lab
Solveig Gaarde Schmidt	PhD Student	Løland lab