Ajith Karunarathne, Ph.D.
Associate Professor
Chemistry
Education
Ph.D. in Biological Chemistry, Michigan State University
Postdoctoral Training in Signal Transduction and Optogenetics, Washington University
School of Medicine
Research Interests
With overlapping focuses on Biological Chemistry, Chemical Biology, and Molecular Pharmacology, our research group takes the reductionist approach when dissecting biological processes at the subcellular level and multiplexing nature-endowed properties of signaling molecules to engineer molecular tools and signaling pathways to uncover the chemistry behind diseases, while fueling discovery and therapy.
We combine cellular signaling and single-cell and subcellular optogenetics to interrogate how cells communicate and behave at the single-cell and subcellular levels. In line with this, we also develop novel optogenetic tools. Our opsin-based optogenetic tool development aims to engineer opsins with optimum spectral, signaling, and chemical properties that are amenable for in vivo applications. We also develop phototropin and cryptochrome-based optogenetic tools for regulating G protein signaling independent of GPCRs. These engineered tools allow the acquisition of dynamic molecular pictures of how crucial signaling pathways are regulated, orchestrating intricate cellular processes, including migration, invasion, and proliferation. We also seek alternative mechanisms to hijack signaling governed by insulin and its receptors to control cellular glucose uptake. Further, using computational and hybrid chemical-cellular approaches, we explore how the bio-available photoreceptor chromophore retinal triggers cytotoxic chemical reactions upon blue light exposure and if and how such cellular chemistry induces vision and skin damage.
We also develop phytopharmacology tools and approaches to overcome the limitations of traditional pharmacotherapy. In this approach, the administration of a photoactivatable molecule is followed by the light irradiation of a precise subcellular, cellular, tissue, or organ location to activate, inhibit or modulate cellular function is pursued.
Publications and Media Placements
Tennakoon M, Senarath K, Kankanamge D, Chadee DN, Karunarathne A. A short C-terminal
peptide in G纬 regulates G尾纬 signaling efficacy. Mol Biol Cell. 2021 Aug 1;32(16):1446-1458.
doi: 10.1091/mbc.E20-11-0750. Epub 2021 Jun 9. PubMed PMID: 34106735; PubMed Central
PMCID: PMC8351738.
Tennakoon M, Senarath K, Kankanamge D, Ratnayake K, Wijayaratna D, Olupothage K, Ubeysinghe S, Martins-Cannavino K, H茅bert TE, Karunarathne A. Subtype-dependent regulation of G尾纬 signaling. Cell Signal. 2021 Jun;82:109947. doi: 10.1016/j.cellsig.2021.109947. Epub 2021 Feb 11. Review. PubMed PMID: 33582184; PubMed Central PMCID: PMC8026654.
Kankanamge D, Ubeysinghe S, Tennakoon M, Pantula PD, Mitra K, Giri L, Karunarathne A. Dissociation of the G protein 尾纬 from the Gq-PLC尾 complex partially attenuates PIP2 hydrolysis. J Biol Chem. 2021 Jan-Jun;296:100702. doi: 10.1016/j.jbc.2021.100702. Epub 2021 Apr 24. PubMed PMID: 33901492; PubMed Central PMCID: PMC8138763.
Geiger M, Janes T, Keshavarz H, Summers S, Pinger C, Fletcher D, Zinn K, Tennakoon M, Karunarathne A, Spence D. A C-peptide complex with albumin and Zn2+ increases measurable GLUT1 levels in membranes of human red blood cells. Sci Rep. 2020 Oct 15;10(1):17493. doi: 10.1038/s41598-020-74527-6. PubMed PMID: 33060722; PubMed Central PMCID: PMC7566639.
Schreidah CM, Ratnayake K, Senarath K, Karunarathne A. Microcystins: Biogenesis, Toxicity, Analysis, and Control. Chem Res Toxicol. 2020 Sep 21;33(9):2225-2246. doi: 10.1021/acs.chemrestox.0c00164. Epub 2020 Jul 29. Review. PubMed PMID: 32614166.
Ratnayake K, Payton JL, Meger ME, Godage NH, Gionfriddo E, Karunarathne A. Blue light-triggered photochemistry and cytotoxicity of retinal. Cell Signal. 2020 May;69:109547. doi: 10.1016/j.cellsig.2020.109547. Epub 2020 Jan 23. PubMed PMID: 31982549; PubMed Central PMCID: PMC7083221.
Kankanamge D, Ratnayake K, Senarath K, Tennakoon M, Harmon E, Karunarathne A. Optical approaches for single-cell and subcellular analysis of GPCR-G protein signaling. Anal Bioanal Chem. 2019 Jul;411(19):4481-4508. doi: 10.1007/s00216-019-01774-6. Epub 2019 Mar 30. Review. PubMed PMID: 30927013; PubMed Central PMCID: PMC6612303.
Kankanamge D, Tennakoon M, Weerasinghe A, Cedeno-Rosario L, Chadee DN, Karunarathne A. G protein 伪q exerts expression level-dependent distinct signaling paradigms. Cell Signal. 2019 Jun;58:34-43. doi: 10.1016/j.cellsig.2019.02.006. Epub 2019 Mar 5. PubMed PMID: 30849518; PubMed Central PMCID: PMC6534355.
Tennakoon M, Kankanamge D, Senarath K, Fasih Z, Karunarathne A. Statins Perturb G尾纬 Signaling and Cell Behavior in a G纬 Subtype Dependent Manner. Mol Pharmacol. 2019 Apr;95(4):361-375. doi: 10.1124/mol.118.114710. Epub 2019 Feb 14. PubMed PMID: 30765461; PubMed Central PMCID: PMC6402420.
Swain S, Gupta RK, Ratnayake K, Priyanka PD, Singh R, Jana S, Mitra K, Karunarathne A, Giri L. Confocal Imaging and k-Means Clustering of GABAB and mGluR Mediated Modulation of Ca2+ Spiking in Hippocampal Neurons. ACS Chem Neurosci. 2018 Dec 19;9(12):3094-3107. doi: 10.1021/acschemneuro.8b00297. Epub 2018 Aug 13. PubMed PMID: 30044088.
Samaradivakara S, Kankanamge D, Senarath K, Ratnayake K, Karunarathne A. G protein 纬 (G纬) subtype dependent targeting of GRK2 to M3 receptor by G尾纬. Biochem Biophys Res Commun. 2018 Sep 3;503(1):165-170. doi: 10.1016/j.bbrc.2018.05.204. Epub 2018 Jun 11. PubMed PMID: 29864421.
Ratnayake K, Payton JL, Lakmal OH, Karunarathne A. Blue light excited retinal intercepts cellular signaling. Sci Rep. 2018 Jul 5;8(1):10207. doi: 10.1038/s41598-018-28254-8. PubMed PMID: 29976989; PubMed Central PMCID: PMC6033873.
Kankanamge D, Ratnayake K, Samaradivakara S, Karunarathne A. Melanopsin (Opn4) utilizes G伪i and G尾纬 as major signal transducers. J Cell Sci. 2018 Jun 5;131(11). doi: 10.1242/jcs.212910. PubMed PMID: 29712722.
Senarath K, Kankanamge D, Samaradivakara S, Ratnayake K, Tennakoon M, Karunarathne A. Regulation of G Protein 尾纬 Signaling. Int Rev Cell Mol Biol. 2018;339:133-191. doi: 10.1016/bs.ircmb.2018.02.008. Epub 2018 Mar 28. Review. PubMed PMID: 29776603.
Senarath K, Payton JL, Kankanamge D, Siripurapu P, Tennakoon M, Karunarathne A. G纬 identity dictates efficacy of G尾纬 signaling and macrophage migration. J Biol Chem. 2018 Feb 23;293(8):2974-2989. doi: 10.1074/jbc.RA117.000872. Epub 2018 Jan 9. PubMed PMID: 29317505; PubMed Central PMCID: PMC5827438.
Siripurapu P, Kankanamge D, Ratnayake K, Senarath K, Karunarathne A. Two independent but synchronized G尾纬 subunit-controlled pathways are essential for trailing-edge retraction during macrophage migration. J Biol Chem. 2017 Oct 20;292(42):17482-17495. doi: 10.1074/jbc.M117.787838. Epub 2017 Sep 1. PubMed PMID: 28864771; PubMed Central PMCID: PMC5655523.
Ratnayake K, Kankanamge D, Senarath K, Siripurapu P, Weis N, Tennakoon M, Payton JL, Karunarathne A. Measurement of GPCR-G protein activity in living cells. Methods Cell Biol. 2017;142:1-25. doi: 10.1016/bs.mcb.2017.07.008. Epub 2017 Sep 19. PubMed PMID: 28964328.
Gupta RK, Swain S, Kankanamge D, Priyanka PD, Singh R, Mitra K, Karunarathne A, Giri L. Comparison of Calcium Dynamics and Specific Features for G Protein-Coupled Receptor-Targeting Drugs Using Live Cell Imaging and Automated Analysis. SLAS Discov. 2017 Aug;22(7):848-858. doi: 10.1177/2472555217693378. Epub 2017 Mar 7. PubMed PMID: 28267930.
Senarath K, Ratnayake K, Siripurapu P, Payton JL, Karunarathne A. Reversible G Protein 尾纬9 Distribution-Based Assay Reveals Molecular Underpinnings in Subcellular, Single-Cell, and Multicellular GPCR and G Protein Activity. Anal Chem. 2016 Dec 6;88(23):11450-11459. doi: 10.1021/acs.analchem.6b02512. Epub 2016 Nov 14. PubMed PMID: 27778511.
Kim S, Barry DM, Liu XY, Yin S, Munanairi A, Meng QT, Cheng W, Mo P, Wan L, Liu SB, Ratnayake K, Zhao ZQ, Gautam N, Zheng J, Karunarathne WK, Chen ZF. Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations. Sci Signal. 2016 Jul 19;9(437):ra71. doi: 10.1126/scisignal.aaf1047. PubMed PMID: 27436359; PubMed Central PMCID: PMC5310287.
Reddy SP, Karunarathne A, Jana S, Giri L. Segmentation of neuron and measurement of optically programmed neurite growth: Fast automation via Bayesian thresholding. IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society. 2015 July; 1100:455-463. doi: 10.1016/j.molstruc.2015.07.064.Karunarathne WK, O'Neill PR, Gautam N. Subcellular optogenetics - controlling signaling and single-cell behavior. J Cell Sci. 2015 Jan 1;128(1):15-25. doi: 10.1242/jcs.154435. Epub 2014 Nov 28. Review. PubMed PMID: 25433038; PubMed Central PMCID: PMC4282045.
Zhao ZQ, Liu XY, Jeffry J, Karunarathne WK, Li JL, Munanairi A, Zhou XY, Li H, Sun YG, Wan L, Wu ZY, Kim S, Huo FQ, Mo P, Barry DM, Zhang CK, Kim JY, Gautam N, Renner KJ, Li YQ, Chen ZF. Descending control of itch transmission by the serotonergic system via 5-HT1A-facilitated GRP-GRPR signaling. Neuron. 2014 Nov 19;84(4):821-34. doi: 10.1016/j.neuron.2014.10.003. Epub 2014 Oct 30. PubMed PMID: 25453842; PubMed Central PMCID: PMC4254557.
Giri L, Patel AK, Karunarathne WK, Kalyanaraman V, Venkatesh KV, Gautam N. A G-protein subunit translocation embedded network motif underlies GPCR regulation of calcium oscillations. Biophys J. 2014 Jul 1;107(1):242-54. doi: 10.1016/j.bpj.2014.05.020. PubMed PMID: 24988358; PubMed Central PMCID: PMC4119271.
O'Neill PR, Giri L, Karunarathne WK, Patel AK, Venkatesh KV, Gautam N. The structure of dynamic GPCR signaling networks. Wiley Interdiscip Rev Syst Biol Med. 2014 Jan-Feb;6(1):115-23. doi: 10.1002/wsbm.1249. Review. PubMed PMID: 24741711; PubMed Central PMCID: PMC4007319.
Karunarathne WK, Giri L, Kalyanaraman V, Gautam N. Optically triggering spatiotemporally confined GPCR activity in a cell and programming neurite initiation and extension. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):E1565-74. doi: 10.1073/pnas.1220697110. Epub 2013 Mar 11. PubMed PMID: 23479634; PubMed Central PMCID: PMC3637763.
Karunarathne WK, Giri L, Patel AK, Venkatesh KV, Gautam N. Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):E1575-83. doi: 10.1073/pnas.1220755110. Epub 2013 Apr 8. PubMed PMID: 23569254; PubMed Central PMCID: PMC3637758.O'Neill PR, Karunarathne WK, Kalyanaraman V, Silvius JR, Gautam N. G-protein signaling leverages subunit-dependent membrane affinity to differentially control 尾纬 translocation to intracellular membranes. Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):E3568-77. doi: 10.1073/pnas.1205345109. Epub 2012 Dec 3. PubMed PMID: 23213235; PubMed Central PMCID: PMC3529095.
Ajith Karunarathne WK, O'Neill PR, Martinez-Espinosa PL, Kalyanaraman V, Gautam N. All G protein 尾纬 complexes are capable of translocation on receptor activation. Biochem Biophys Res Commun. 2012 May 11;421(3):605-11. doi: 10.1016/j.bbrc.2012.04.054. Epub 2012 Apr 19. PubMed PMID: 22538369; PubMed Central PMCID: PMC3351579.Cho JH, Saini DK, Karunarathne WK, Kalyanaraman V, Gautam N. Alteration of Golgi structure in senescent cells and its regulation by a G protein 纬 subunit. Cell Signal. 2011 May;23(5):785-93. doi: 10.1016/j.cellsig.2011.01.001. Epub 2011 Jan 14. PubMed PMID: 21238584; PubMed Central PMCID: PMC3085901.
Saini DK, Karunarathne WK, Angaswamy N, Saini D, Cho JH, Kalyanaraman V, Gautam N. Regulation of Golgi structure and secretion by receptor-induced G protein 尾纬 complex translocation. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11417-22. doi: 10.1073/pnas.1003042107. Epub 2010 Jun 7. PubMed PMID: 20534534; PubMed Central PMCID: PMC2895111.