Henri Leinonen, PhD
Doctor of Pharmacy and Neurobiology, Master of Pharmacology; University of Eastern Finland
Neurobiology, neurodegeneration, neuroimaging, eye research, neuroscience, retina
Description
New member of the ICTER ISC for the term 2024-2028, Dr. Leinonen’s research focuses on two projects: (1) investigation of a novel drug repurposing-strategy for the treatment of retinal degenerations (RD); (2) Homeostatic plasticity in the retina, its molecular mechanisms and implications for functional adaptation.
His group’s drug discovery program uses repurposed GPCR drugs. The researchers led by Dr. Leinonen have shown that a treatment with a combination therapy comprised of three GPCR-drugs slows progressive RD (Leinonen et al. 2024, Nat Commun). The next crucial task is to uncover the therapeutic mechanisms of our therapy. This will facilitate further development of the treatment concept, launch innovative drug development pipelines, as well as advance the concept to clinical evaluation.
Dr. Leinonen’s research team detected retinal adaptability to sensory defect in 2013 and their first paper related to this was published in 2020 (Leinonen et al., eLife). Next, they aim to solve the molecular pathways enabling retinal homeostatic plasticity. This knowledge can help to find mechanisms of how the CNS adapts to injury and malfunction and can guide pharmacotherapies.
Dr. Leinonen and his group use the retina as a model tissue for plasticity, pharmacology and drug discovery research for several reasons, such as amenability for noninvasive imaging due to eye’s transparency, finely layered structure and well-characterized structure-function relationships, functional similarity to that of brain due to same neurodevelopmental origin. Arguably, the retina is the best-characterized neuronal system in the body.
Publication list
- Tanoli Z, Fernández-Torras A, Özcan UO, Kushnir A, Nader KM, Gadiya Y, Fiorenza L, Ianevski A, Vähä-Koskela M, Miihkinen M, Seemab U, Leinonen H, Seashore-Ludlow B, Tampere M, Kalman A, Ballante F, Benfenati E, Saunders G, Potdar S, Gómez García I, García-Serna R, Talarico C, Beccari AR, Schaal W, Polo A, Costantini S, Cabri E, Jacobs M, Saarela J, Budillon A, Spjuth O, Östling P, Xhaard H, Quintana J, Mestres J, Gribbon P, Ussi AE, Lo DC, de Kort M, Wennerberg K, Fratelli M, Carreras-Puigvert J, Aittokallio T. Computational drug repurposing: approaches, evaluation of in silico resources and case studies. Nat Rev Drug Discov. 2025 Mar 18. doi: 10.1038/s41573-025-01164-x. Online ahead of print.
- Montaser AB, Gao F, Peters D, Vainionpää K, Zhibin N, Skowronska-Krawczyk D, Figeys D, Palczewski K, Leinonen H. Retinal Proteome Profiling of Inherited Retinal Degeneration Across Three Different Mouse Models Suggests Common Drug Targets in Retinitis Pigmentosa. Mol Cell Proteomics. 2024 Nov;23(11):100855. doi: 10.1016/j.mcpro.2024.100855. Epub 2024 Oct 9.
- Pazur EJ, Kalatanova A, Tasker NR, Vainionpää K, Leinonen H, Wipf P. Synthesis and Biological Analysis of Iso-dimethyltryptamines in a Model of Light-Induced Retinal Degeneration. ACS Med Chem Lett. 2024 Jun 13;15(7):1049-1056. doi: 10.1021/acsmedchemlett.4c00130. PMID: 39015263; PMCID: PMC11247652.
- Leinonen H, Zhang J, Occelli LM, Seemab U, Choi EH, L P Marinho LF, Querubin J, Kolesnikov AV, Galinska A, Kordecka K, Hoang T, Lewandowski D, Lee TT, Einstein EE, Einstein DE, Dong Z, Kiser PD, Blackshaw S, Kefalov VJ, Tabaka M, Foik A, Petersen-Jones SM, Palczewski K. A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models. Nat Commun. 2024 Jul 15;15(1):5943. doi: 10.1038/s41467-024-50033-5. PMID: 39009597; PMCID: PMC11251169.
- Ala-Nisula T, Halmetoja R, Leinonen H, Kurkela M, Lipponen HR, Sakko S, Karpale M, Salo AM, Sissala N, Röning T, Raza GS, Mäkelä KA, Thevenot J, Herzig KH, Serpi R, Myllyharju J, Tanila H, Koivunen P, Dimova EY. Metabolic characteristics of transmembrane prolyl 4-hydroxylase (P4H-TM) deficient mice. Pflugers Arch. 2024 Feb 24. doi: 10.1007/s00424-024-02920-5. Epub ahead of print. PMID: 38396259.
- Gao J, Leinonen H, Wang EJ, Ding M, Perry G, Palczewski K, Wang X. Sex-Specific Early Retinal Dysfunction in Mutant TDP-43 Transgenic Mice. J Alzheimers Dis. 2024;97(2):927-937. doi: 10.3233/JAD-231102. PMID: 38143367; PMCID: PMC11174142.
- Luu JC, Saadane A, Leinonen H, Choi EH, Gao F, Lewandowski D, Halabi M, Sander CL, Wu A, Wang JM, Singh R, Gao S, Lessieur EM, Dong Z, Palczewska G, Mullins RF, Peachey NS, Kiser PD, Tabaka M, Kern TS, Palczewski K. Stress resilience-enhancing drugs preserve tissue structure and function in degenerating retina via phosphodiesterase inhibition. Proc Natl Acad Sci U S A. 2023 May 9;120(19):e2221045120. doi: 10.1073/pnas.2221045120. Epub 2023 May 1. PMID: 37126699; PMCID: PMC10175720.
- Leinonen HO, Bull E, Fu Z. Neural and Müller glial adaptation of the retina to photoreceptor degeneration. Neural Regen Res. 2023 Apr;18(4):701-707. doi: 10.4103/1673-5374.354511. PMID: 36204825; PMCID: PMC9700092.
- Huh CYL, Leinonen H, Nakayama T, Tomasello JR, Zhang J, Zeitoun J, Peach JP, Halabi M, Kiser JZ, Palczewski K, Kiser PD, Gandhi SP. Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration. Curr Biol. 2022 Oct 24;32(20):4538-4546.e5. doi: 10.1016/j.cub.2022.09.005. Epub 2022 Sep 23. PMID: 36152631; PMCID: PMC10083103.
- Leinonen H, Lyon DC, Palczewski K, Foik AT. Visual System Hyperexcitability and Compromised V1 Receptive Field Properties in Early-Stage Retinitis Pigmentosa in Mice. eNeuro. 2022 Jun 27;9(3):ENEURO.0107-22.2022. doi: 10.1523/ENEURO.0107-22.2022. PMID: 35701168; PMCID: PMC9239850.
- Choi EH, Suh S, Foik AT, Leinonen H, Newby GA, Gao XD, Banskota S, Hoang T, Du SW, Dong Z, Raguram A, Kohli S, Blackshaw S, Lyon DC, Liu DR, Palczewski K. In vivo base editing rescues cone photoreceptors in a mouse model of early-onset inherited retinal degeneration. Nat Commun. 2022 Apr 5;13(1):1830. doi:10.1038/s41467-022-29490-3. PMID: 35383196; PMCID: PMC8983734.
- Lewandowski D, Foik AT, Smidak R, Choi EH, Zhang J, Hoang T, Tworak A, Suh S, Leinonen H, Dong Z, Pinto AF, Tom E, Luu J, Lee J, Ma X, Bieberich E, Blackshaw S, Saghatelian A, Lyon DC, Skowronska-Krawczyk D, Tabaka M, Palczewski Inhibition of ceramide accumulation in AdipoR1-/- mice increases photoreceptor survival and improves vision. JCI Insight. 2022 Feb 22;7(4):e156301. doi: 10.1172/jci.insight.156301. PMID: 35015730; PMCID: PMC8876453.
- Cheng C, Weiss L, Leinonen H, Shmara A, Yin HZ, Ton T, Do A, Lee J, Ta L, Mohanty E, Vargas J, Weiss J, Palczewski K, Kimonis V. VCP/p97 inhibitor CB-5083 modulates muscle pathology in a mouse model of VCP inclusion body myopathy. J Transl Med. 2022 Jan 8;20(1):21. doi: 10.1186/s12967-021-03186-6. PMID: 34998409; PMCID: PMC8742393.
- Kern TS, Du Y, Tang J, Lee CA, Liu H, Dreffs A, Leinonen H, Antonetti DA, Palczewski K. Regulation of Adrenergic, Serotonin, and Dopamine Receptors to Inhibit Diabetic Retinopathy: Monotherapies versus Combination Therapies. Mol Pharmacol. 2021 Nov;100(5):470-479. doi: 10.1124/molpharm.121.000278. Epub 2021 Aug 15. PMID: 34393108; PMCID: PMC9175131.
- Leinonen H, Cheng C, Pitkänen M, Sander CL, Zhang J, Saeid S, Turunen T, Shmara A, Weiss L, Ta L, Ton T, Koskelainen A, Vargas JD, Kimonis V, Palczewski A p97/Valosin-Containing Protein Inhibitor Drug CB-5083 Has a Potent but Reversible Off-Target Effect on Phosphodiesterase-6. J Pharmacol Exp Ther. 2021 Jul;378(1):31-41. doi: 10.1124/jpet.120.000486. Epub 2021 Apr 30. PMID: 33931547; PMCID: PMC8456514.
- Choi EH, Suh S, Einstein DE, Leinonen H, Dong Z, Rao SR, Fliesler SJ, Blackshaw S, Yu M, Peachey NS, Palczewski K, Kiser PD. An inducible Cre mouse for studying roles of the RPE in retinal physiology and disease. JCI Insight. 2021 May 10;6(9):e146604. doi: 10.1172/jci.insight.146604. PMID: 33784255; PMCID: PMC8262343.
- Suh S, Choi EH, Leinonen H, Foik AT, Newby GA, Yeh WH, Dong Z, Kiser PD, Lyon DC, Liu DR, Palczewski K. Restoration of visual function in adult mice with an inherited retinal disease via adenine base editing. Nat Biomed Eng. 2021 Feb;5(2):169-178. doi: 10.1038/s41551-020-00632-6. Epub 2020 Oct 19. Erratum in: Nat Biomed Eng. 2020 Nov;4(11):1119. doi: 10.1038/s41551-020-00652-2. PMID: 33077938; PMCID: PMC7885272.
- Leinonen H, Pham NC, Boyd T, Santoso J, Palczewski K, Vinberg F. Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease. Elife. 2020 Sep 22;9:e59422. doi: 10.7554/eLife.59422. PMID: 32960171; PMCID: PMC7529457.
- Choi EH, Daruwalla A, Suh S, Leinonen H, Palczewski K. Retinoids in the visual cycle: role of the retinal G protein-coupled receptor. J Lipid Res. 2021;62:100040. doi: 10.1194/jlr.TR120000850. Epub 2021 Feb 6. PMID: 32493732; PMCID: PMC7910522.
- Zhang J, Choi EH, Tworak A, Salom D, Leinonen H, Sander CL, Hoang TV, Handa JT, Blackshaw S, Palczewska G, Kiser PD, Palczewski K. Photic generation of 11-<i>cis</i>-retinal in bovine retinal pigment epithelium. J Biol Chem. 2019 Dec 13;294(50):19137-19154. doi: 10.1074/jbc.RA119.011169. Epub 2019 Nov 6. PMID: 31694912; PMCID: PMC6916499.
- Singh Y, Leinonen H, Fazaludeen F, Jaronen M, Guest D, Buckley N, Byts N, Oksa P, Jalkanen K, Iqbal I, Huuskonen M, Savchenko E, Keksa-Goldsteine V, Chew S, Myllyharju J, Tanila H, Ooi L, Koistinaho J, Kanninen KM, Malm T. Loss of Cln5 leads to altered Gad1 expression and deficits in interneuron development in mice. Hum Mol Genet. 2019 Oct 1;28(19):3309-3322. doi: 10.1093/hmg/ddz165. PMID: 31294445.
- Leinonen H, Koivisto H, Lipponen HR, Matilainen A, Salo AM, Dimova EY, Hämäläinen E, Stavén S, Miettinen P, Myllyharju J, Koivunen P, Tanila H. Null mutation in P4h-tm leads to decreased fear and anxiety and increased social behavior in mice. Neuropharmacology. 2019 Jul 15;153:63-72. doi: 10.1016/j.neuropharm.2019.04.023. Epub 2019 Apr 25. PMID: 31029587.
- Leinonen H, Choi EH, Gardella A, Kefalov VJ, Palczewski K. A Mixture of U.S. Food and Drug Administration-Approved Monoaminergic Drugs Protects the Retina From Light Damage in Diverse Models of Night Blindness. Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1442-1453. doi: 10.1167/iovs.19-26560. PMID: 30947334; PMCID: PMC6736410.
- Felszeghy S, Viiri J, Paterno JJ, Hyttinen JMT, Koskela A, Chen M, Leinonen H, Tanila H, Kivinen N, Koistinen A, Toropainen E, Amadio M, Smedowski A, Reinisalo M, Winiarczyk M, Mackiewicz J, Mutikainen M, Ruotsalainen AK, Kettunen M, Jokivarsi K, Sinha D, Kinnunen K, Petrovski G, Blasiak J, Bjørkøy G, Koskelainen A, Skottman H, Urtti A, Salminen A, Kannan R, Ferrington DA, Xu H, Levonen AL, Tavi P, Kauppinen A, Kaarniranta K. Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration. Redox Biol. 2019 Jan;20:1-12. doi: 10.1016/j.redox.2018.09.011. Epub 2018 Sep 14. PMID: 30253279; PMCID: PMC6156745.
- Orban T, Leinonen H, Getter T, Dong Z, Sun W, Gao S, Veenstra A, Heidari- Torkabadi H, Kern TS, Kiser PD, Palczewski K. A Combination of G Protein-Coupled Receptor Modulators Protects Photoreceptors from Degeneration. J Pharmacol Exp Ther. 2018 Feb;364(2):207-220. doi: 10.1124/jpet.117.245167. Epub 2017 Nov 21. PMID: 29162627; PMCID: PMC5771314.
- Leinonen H, Tanila H. Vision in laboratory rodents-Tools to measure it and implications for behavioral research. Behav Brain Res. 2018 Oct 15;352:172-182. doi: 10.1016/j.bbr.2017.07.040. Epub 2017 Jul 29. PMID: 28760697.
- Leinonen H, Keksa-Goldsteine V, Ragauskas S, Kohlmann P, Singh Y, Savchenko E, Puranen J, Malm T, Kalesnykas G, Koistinaho J, Tanila H, Kanninen KM. Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy. Sci Rep. 2017 May 9;7(1):1597. doi: 10.1038/s41598-017-01716-1. PMID: 28487519; PMCID: PMC5431647.
- Leinonen H, Rossi M, Salo AM, Tiainen P, Hyvärinen J, Pitkänen M, Sormunen R, Miinalainen I, Zhang C, Soininen R, Kivirikko KI, Koskelainen A, Tanila H, Myllyharju J, Koivunen P. Lack of P4H-TM in mice results in age-related retinal and renal alterations. Hum Mol Genet. 2016 Sep 1;25(17):3810-3823. doi: 10.1093/hmg/ddw228. Epub 2016 Jul 27. PMID: 27466183.
- Lemarchant S, Dunghana H, Pomeshchik Y, Leinonen H, Kolosowska N, Korhonen P, Kanninen KM, García-Berrocoso T, Montaner J, Malm T, Koistinaho J. Anti-inflammatory effects of ADAMTS-4 in a mouse model of ischemic stroke. Glia. 2016 Sep;64(9):1492-507. doi: 10.1002/glia.23017. Epub 2016 Jun 15. PMID: 27301579.
- Koivisto H, Leinonen H, Puurula M, Hafez HS, Barrera GA, Stridh MH, Waagepetersen HS, Tiainen M, Soininen P, Zilberter Y, Tanila H. Chronic Pyruvate Supplementation Increases Exploratory Activity and Brain Energy Reserves in Young and Middle-Aged Mice. Front Aging Neurosci. 2016 Mar 16;8:41. doi: 10.3389/fnagi.2016.00041. Erratum in: Front Aging Neurosci. 2017 Mar 20;9:67. doi: 10.3389/fnagi.2017.00067. PMID: 27014054; PMCID: PMC4794631.
- Leinonen H, Lipponen A, Gurevicius K, Tanila H. Normal Amplitude of Electroretinography and Visual Evoked Potential Responses in AβPP/PS1 Mice. J Alzheimers Dis. 2016;51(1):21-6. doi: 10.3233/JAD-150798. PMID: 26836173.
- Ragauskas S, Leinonen H, Puranen J, Rönkkö S, Nymark S, Gurevicius K, Lipponen A, Kontkanen O, Puoliväli J, Tanila H, Kalesnykas G. Early retinal function deficit without prominent morphological changes in the R6/2 mouse model of Huntington’s disease. PLoS One. 2014 Dec 3;9(12):e113317. doi: 10.1371/journal.pone.0113317. PMID: 25469887; PMCID: PMC4254453.