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David M. MacLean, Ph.D.

David M. MacLean, Ph.D.

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Office (585) 276-3032

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Macleanlab.net

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About Me

Faculty Appointments

Associate Professor - Department of Pharmacology and Physiology (SMD)

Paul Stark Professorship in Pharmacology - Department of Pharmacology and Physiology (SMD)

Credentials

Post-doctoral Training & Residency

UTHealth Science Center, Dept. of Biochemistry and Molecular Biology 2012 - 2017

Education

PhD | Canada-McGill University. Pharmacology. 2011

BSc | Canada - University of Toronto. Neuroscience. 2005

Awards

Paul F. Cranefield Postdoctoral Award.

Research

Dr. MacLean's research program aims to understand the inter-relationships between ligand-gated ion channel form, function and physiology. Currently, the lab is focused on acid-sensing ion channels (ASICs), a class of pH-activated channels expressed throughout the brain and body. Another ongoing rese...
Dr. MacLean's research program aims to understand the inter-relationships between ligand-gated ion channel form, function and physiology. Currently, the lab is focused on acid-sensing ion channels (ASICs), a class of pH-activated channels expressed throughout the brain and body. Another ongoing research interest is ionotropic glutamate receptors (ie. AMPA, NMDA and Kainate receptors). To study these receptors, the lab uses a combination of electrophysiology, fluorescence spectroscopy, protein purification, kinetic and molecular modelling as well as non-canonical amino acid incorporation.

Publications

Journal Articles

Inositol 1,4,5-Trisphosphate Receptor Mutations Associated with Human Disease: Insights into Receptor Function and Dysfunction.

Arige V, MacLean DM, Yule DI

Annual review of physiology.. 2025 February 87 (1):201-228. Epub 02/03/2025.

Clinical features, functional consequences, and rescue pharmacology of missense GRID1 and GRID2 human variants.

Allen JP, Garber KB, Perszyk R, Khayat CT, Kell SA, Kaneko M, Quindipan C, Saitta S, Ladda RL, Hewson S, Inbar-Feigenberg M, Prasad C, Prasad AN, Olewiler L, Mu W, Rosenthal LS, Scala M, Striano P, Zara F, McCullock TW, Jauss RT, Lemke JR, MacLean DM, Zhu C, Yuan H, Myers SJ, Traynelis SF

Human molecular genetics.. 2024 February 133 (4):355-373. Epub 1900 01 01.

Photomodulation of the ASIC1a acidic pocket destabilizes the open state.

Rook ML, McCullock TW, Couch T, Lueck JD, MacLean DM

Protein science : a publication of the Protein Society.. 2023 November 32 (11):e4800. Epub 1900 01 01.

Mutation of a conserved glutamine residue does not abolish desensitization of acid-sensing ion channel 1.

Rook ML, Miaro M, Couch T, Kneisley DL, Musgaard M, MacLean DM

The Journal of general physiology.. 2021 August 2153 (8)Epub 06/01/2021.

Topography and motion of acid-sensing ion channel intracellular domains.

Couch T, Berger K, Kneisley DL, McCullock TW, Kammermeier P, Maclean DM

eLife.. 2021 July 2210 Epub 07/22/2021.

Coupling structure with function in acid-sensing ion channels: challenges in pursuit of proton sensors.

Rook ML, Musgaard M, MacLean DM

The Journal of physiology.. 2021 January 599 (2):417-430. Epub 05/20/2020.

Molecular Investigation of Chicken Acid-Sensing Ion Channel 1 ?11-12 Linker Isomerization and Channel Kinetics.

Rook ML, Ananchenko A, Musgaard M, MacLean DM

Frontiers in cellular neuroscience.. 2021 15 :761813. Epub 11/24/2021.

Conformational spread and dynamics in allostery of NMDA receptors.

Durham RJ, Paudyal N, Carrillo E, Bhatia NK, Maclean DM, Berka V, Dolino DM, Gorfe AA, Jayaraman V

Proceedings of the National Academy of Sciences of the United States of America.. 2020 February 18117 (7):3839-3847. Epub 02/03/2020.

?11-12 linker isomerization governs acid-sensing ion channel desensitization and recovery.

Rook ML, Williamson A, Lueck JD, Musgaard M, Maclean DM

eLife.. 2020 February 79 Epub 02/07/2020.

Mechanism of modulation of AMPA receptors by TARP-?8.

Jayaraman V, Nowak LM, MacLean DM, Lee G, Litwin DB, Durham RJ, Berka V, Shaikh SA, Carrillo E

The Journal of general physiology.. 2020 January 6152 (1)Epub 1900 01 01.

Comparing the performance of mScarlet-I, mRuby3, and mCherry as FRET acceptors for mNeonGreen.

McCullock TW, MacLean DM, Kammermeier PJ

PloS one.. 2020 15 (2):e0219886. Epub 02/05/2020.

Mapping the Conformational Landscape of Glutamate Receptors Using Single Molecule FRET.

MacLean DM, Durham RJ, Jayaraman V

Trends in neurosciences.. 2019 February 42 (2):128-139. Epub 10/29/2018.

The ?2?-1-NMDA Receptor Complex Is Critically Involved in Neuropathic Pain Development and Gabapentin Therapeutic Actions.

Chen J, Li L, Chen SR, Chen H, Xie JD, Sirrieh RE, MacLean DM, Zhang Y, Zhou MH, Jayaraman V, Pan HL

Cell reports.. 2018 February 2722 (9):2307-2321. Epub 1900 01 01.

The structure-energy landscape of NMDA receptor gating.

Dolino DM, Chatterjee S, MacLean DM, Flatebo C, Bishop LDC, Shaikh SA, Landes CF, Jayaraman V

Nature chemical biology.. 2017 December 13 (12):1232-1238. Epub 10/09/2017.

Dual Effects of TARP ?-2 on Glutamate Efficacy Can Account for AMPA Receptor Autoinactivation.

Coombs ID, MacLean DM, Jayaraman V, Farrant M, Cull-Candy SG

Cell reports.. 2017 August 120 (5):1123-1135. Epub 1900 01 01.

Deactivation kinetics of acid-sensing ion channel 1a are strongly pH-sensitive.

MacLean DM, Jayaraman V

Proceedings of the National Academy of Sciences of the United States of America.. 2017 March 21114 (12):E2504-E2513. Epub 03/06/2017.

Dynamic Lipid-dependent Modulation of Protein Topology by Post-translational Phosphorylation.

Vitrac H, MacLean DM, Karlstaedt A, Taegtmeyer H, Jayaraman V, Bogdanov M, Dowhan W

The Journal of biological chemistry.. 2017 February 3292 (5):1613-1624. Epub 12/14/2016.

Stargazin Modulation of AMPA Receptors.

Shaikh SA, Dolino DM, Lee G, Chatterjee S, MacLean DM, Flatebo C, Landes CF, Jayaraman V

Cell reports.. 2016 October 417 (2):328-335. Epub 1900 01 01.

Acid-sensing ion channels are tuned to follow high-frequency stimuli.

MacLean DM, Jayaraman V

The Journal of physiology.. 2016 May 15594 (10):2629-45. Epub 04/10/2016.

Dynamic membrane protein topological switching upon changes in phospholipid environment.

Vitrac H, MacLean DM, Jayaraman V, Bogdanov M, Dowhan W

Proceedings of the National Academy of Sciences of the United States of America.. 2015 November 10112 (45):13874-9. Epub 10/28/2015.

A conserved structural mechanism of NMDA receptor inhibition: A comparison of ifenprodil and zinc.

Sirrieh RE, MacLean DM, Jayaraman V

The Journal of general physiology.. 2015 August 146 (2):173-81. Epub 07/13/2015.

Subtype-dependent N-methyl-D-aspartate receptor amino-terminal domain conformations and modulation by spermine.

Sirrieh RE, MacLean DM, Jayaraman V

The Journal of biological chemistry.. 2015 May 15290 (20):12812-20. Epub 03/31/2015.

Stargazin promotes closure of the AMPA receptor ligand-binding domain.

MacLean DM, Ramaswamy SS, Du M, Howe JR, Jayaraman V

The Journal of general physiology.. 2014 December 144 (6):503-12. Epub 1900 01 01.

RNA based antagonist of NMDA receptors.

Lee G, MacLean DM, Ulrich H, Zhao X, Aronowski J, Jayaraman V

ACS chemical neuroscience.. 2014 July 165 (7):559-67. Epub 04/16/2014.

Proton-mediated conformational changes in an acid-sensing ion channel.

Ramaswamy SS, MacLean DM, Gorfe AA, Jayaraman V

The Journal of biological chemistry.. 2013 December 13288 (50):35896-903. Epub 11/06/2013.

Amino-terminal domain tetramer organization and structural effects of zinc binding in the N-methyl-D-aspartate (NMDA) receptor.

Sirrieh RE, MacLean DM, Jayaraman V

The Journal of biological chemistry.. 2013 August 2288 (31):22555-64. Epub 06/21/2013.

CrossTalk opposing view: TARPs modulate AMPA receptor conformations before the gating transitions.

MacLean DM

The Journal of physiology.. 2013 April 1591 (7):1585-6; discussion 1587. Epub 1900 01 01.

Role of conformational dynamics in ?-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor partial agonism.

Ramaswamy S, Cooper D, Poddar N, MacLean DM, Rambhadran A, Taylor JN, Uhm H, Landes CF, Jayaraman V

The Journal of biological chemistry.. 2012 December 21287 (52):43557-64. Epub 10/31/2012.

Transmembrane AMPA receptor regulatory protein regulation of competitive antagonism: a problem of interpretation.

Maclean DM, Bowie D

The Journal of physiology.. 2011 November 15589 (Pt 22):5383-90. Epub 10/03/2011.

Cations but not anions regulate the responsiveness of kainate receptors.

Maclean DM, Wong AY, Fay AM, Bowie D

The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2011 February 931 (6):2136-44. Epub 1900 01 01.

The delta2 glutamate-like receptor undergoes similar conformational changes as other ionotropic glutamate receptors.

MacLean DM

The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2009 May 2729 (21):6767-8. Epub 1900 01 01.

Na+/Cl- dipole couples agonist binding to kainate receptor activation.

Wong AY, MacLean DM, Bowie D

The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2007 June 2027 (25):6800-9. Epub 1900 01 01.

Ancestral reconstruction of the ligand-binding pocket of Family C G protein-coupled receptors.

Kuang D, Yao Y, Maclean D, Wang M, Hampson DR, Chang BS

Proceedings of the National Academy of Sciences of the United States of America.. 2006 September 19103 (38):14050-5. Epub 09/11/2006.

Books

Ionotropic Glutamate Receptor Technologies (2015)

Chapter: Constructing a rapid solution exchange system