Kasturi Roy, PhD
Research Associate 1About
Research
Publications
2023
Inactivation of Ire1alpha Endoribonuclease Domain Slows Down ADPKD in Orthologous Mouse Models
Bhardwaj R, Volpe I, Yilmaz D, Pioppini C, Roy K, Rehman M, Cai Y, Krappitz M, Somlo S, Fedeles S. Inactivation of Ire1alpha Endoribonuclease Domain Slows Down ADPKD in Orthologous Mouse Models. Journal Of The American Society Of Nephrology 2023, 34: 19-19. DOI: 10.1681/asn.20233411s119b.Peer-Reviewed Original ResearchStructure-based discovery of conformationally selective inhibitors of the serotonin transporter
Singh I, Seth A, Billesbølle C, Braz J, Rodriguiz R, Roy K, Bekele B, Craik V, Huang X, Boytsov D, Pogorelov V, Lak P, O'Donnell H, Sandtner W, Irwin J, Roth B, Basbaum A, Wetsel W, Manglik A, Shoichet B, Rudnick G. Structure-based discovery of conformationally selective inhibitors of the serotonin transporter. Cell 2023, 186: 2160-2175.e17. PMID: 37137306, PMCID: PMC10306110, DOI: 10.1016/j.cell.2023.04.010.Peer-Reviewed Original Research
2022
Pkd2 Re-Expression Can Reverse Liver Cysts and Improve GFR in Mouse Models of Autosomal Dominant Polycystic Kidney Disease
Dong K, Tham M, Cordido A, Cai Y, Pei S, Bhardwaj R, Wei Z, Rehman M, Roy K, Tian X, Somlo S. Pkd2 Re-Expression Can Reverse Liver Cysts and Improve GFR in Mouse Models of Autosomal Dominant Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2022, 33: 418-418. DOI: 10.1681/asn.20223311s1418c.Peer-Reviewed Original ResearchStructural basis for inhibition of the Cation-chloride cotransporter NKCC1 by the diuretic drug bumetanide
Zhao Y, Roy K, Vidossich P, Cancedda L, De Vivo M, Forbush B, Cao E. Structural basis for inhibition of the Cation-chloride cotransporter NKCC1 by the diuretic drug bumetanide. Nature Communications 2022, 13: 2747. PMID: 35585053, PMCID: PMC9117670, DOI: 10.1038/s41467-022-30407-3.Peer-Reviewed Original ResearchConceptsTranslocation pathwayElectron cryo-microscopy structureC-terminal domainIon translocation pathwayCation-chloride cotransporters NKCC1Transmembrane domainCotransporter NKCC1C-terminal domain interactionsStructural basisDomain interactionsRenal salt reabsorptionDomain associationConformational changesFunctional studiesIon translocationElectroneutral symportCell membraneNKCC1PathwayNKCC2DomainSalt reabsorptionTransmembraneTranslocationTransporters
2021
The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2
Zhang S, Zhou J, Zhang Y, Liu T, Friedel P, Zhuo W, Somasekharan S, Roy K, Zhang L, Liu Y, Meng X, Deng H, Zeng W, Li G, Forbush B, Yang M. The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2. Communications Biology 2021, 4: 226. PMID: 33597714, PMCID: PMC7889885, DOI: 10.1038/s42003-021-01750-w.Peer-Reviewed Original ResearchConceptsCryo-electron microscopy structureHuman NKCC1Microscopy structureEssential residuesFunctional characterizationKCC transportersPlasma membraneStructural basisTransepithelial saltTransport activityMechanistic understandingTransportersStructural studiesCritical roleCotransporter NKCC1Computational analysisIon transportWater transportNeuronal excitabilityNKCC1PhosphorylationCell volumeNKCCKCC2Residues
2019
Lipid Modifications in Cilia Biology
Roy K, Marin EP. Lipid Modifications in Cilia Biology. Journal Of Clinical Medicine 2019, 8: 921. PMID: 31252577, PMCID: PMC6678300, DOI: 10.3390/jcm8070921.BooksLipid modificationCiliary proteinsCiliary protein traffickingSpecific protein poolsDifferent lipid modificationsCilia biologyProtein traffickingProtein stabilitySignaling cascadesTransporter proteinsProtein poolProteinVariety of rolesCiliaTraffickingFinal localizationCellular structureDistinctive roleBiologyRoleAbundanceModificationRegulationPathwayCascadeReceptor tyrosine kinases (RTKs) consociate in regulatory clusters in Alzheimer’s disease and type 2 diabetes
Majumder P, Roy K, Bagh S, Mukhopadhyay D. Receptor tyrosine kinases (RTKs) consociate in regulatory clusters in Alzheimer’s disease and type 2 diabetes. Molecular And Cellular Biochemistry 2019, 459: 171-182. PMID: 31154588, DOI: 10.1007/s11010-019-03560-5.Peer-Reviewed Original ResearchConceptsType 2 diabetesAlzheimer's diseaseReceptor tyrosine kinasesPost-mortem Alzheimer's diseaseFuture therapeutic developmentInsulin resistanceDisease typeActivity statusDiseaseCommon hallmarkTherapeutic developmentDefinitive roleDiabetesOne-thirdTyrosine kinaseCell modelSimilar regulatory mechanismsT2D.Regulatory mechanisms
2018
Polycystin-1, the product of the polycystic kidney disease gene PKD1, is post-translationally modified by palmitoylation
Roy K, Marin EP. Polycystin-1, the product of the polycystic kidney disease gene PKD1, is post-translationally modified by palmitoylation. Molecular Biology Reports 2018, 45: 1515-1521. PMID: 30073588, DOI: 10.1007/s11033-018-4224-6.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseProteins polycystin-1End-stage renal diseasePossible pharmacologic targetsStage renal diseasePossible modifiable factorsRate of progressionDominant polycystic kidney diseaseExpression levelsPolycystic kidney diseaseRenal diseaseKidney diseaseModifiable factorsCommon causePharmacologic targetPolycystin-1Carboxyl-terminal fragmentKidney cystsPC1 expressionPotential causesDiseaseDistinct mutationsPost-translational modificationsMultiple complementary approachesGenes PKD1
2017
Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation
Roy K, Jerman S, Jozsef L, McNamara T, Onyekaba G, Sun Z, Marin EP. Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation. Journal Of Biological Chemistry 2017, 292: 17703-17717. PMID: 28848045, PMCID: PMC5663873, DOI: 10.1074/jbc.m117.792937.Peer-Reviewed Original ResearchConceptsPost-translational attachmentMost mammalian cellsCiliary GTPase Arl13bCilia localizationProtein palmitoylationCiliary proteinsCilia proteinsProtein localizationCilia formationMammalian cellsCilia functionPalmitoylationPrimary ciliaPlasma membraneCilia resorptionArl13bFunctional importanceMyristoylationCiliaCritical roleProteinMouse kidneyLocalizationDepalmitoylationCellsCellular levels of Grb2 and cytoskeleton stability are correlated in a neurodegenerative scenario
Majumder P, Roy K, Singh BK, Jana NR, Mukhopadhyay D. Cellular levels of Grb2 and cytoskeleton stability are correlated in a neurodegenerative scenario. Disease Models & Mechanisms 2017, 10: 655-669. PMID: 28360125, PMCID: PMC5451165, DOI: 10.1242/dmm.027748.Peer-Reviewed Original ResearchConceptsAD-like conditionsDisease manifestCytoskeletal architecturePak1 proteinCytoskeleton stabilityAD mouse brainCytoskeletal proteinsGrb2 overexpressionGrb2Β-amyloid oligomersPotential new strategyCellular levelNeuronal lossAD patientsPreventive roleCytoskeletonProteinMouse brainBrain tissueExtracellular accumulationPotent inducerMolecular featuresUnique roleDomain levelCytoskeletal