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Profile

Thomas Kukar PhD

  • Department of Pharmacology & Chemical Biology
    Associate Professor
  • (404) 727-5991
  • thomas.kukar@emory.edu
  • My Research Gate Profile
  • My Lab Website
  • My Google Scholar Page
  • Emory University School of Medicine
    Pharmacology
    1510 Clifton Rd NE, RRC5170
Head shot of Thomas Kukar

Overview

Neurodegeneration, Alzheimer's disease, Frontotemporal dementia, Amyotrophic Lateral Sclerosis, Drug discovery

Academic Appointment

  • Assistant Professor, Department of Neurology, Emory University School of Medicine
  • Assistant Professor, Department of Pharmacology, Emory University, School of Medicine

Education

Degrees

  • PhD from University of Florida
  • BS from University of Florida

Research

Focus

  • My long term research interest is the development of efficacious therapies for neurodegenerative diseases. One major research focus is to understand the pathogenesis of neurodegeneration by studying how mutations in genes lead to Alzheimers disease, frontotemporal dementia, or amyotrophic lateral sclerosis. The goal is to use this knowledge to identify new drug targets and lead compounds.

Publications

  • Granulins rescue inflammation, lysosome dysfunction, lipofuscin, and neuropathology in a mouse model of progranulin deficiency.
    Cell Rep Volume: 43 Page(s): 114985
    12/24/2024 Authors: Root J; Mendsaikhan A; Taylor G; Merino P; Nandy S; Wang M; Araujo LT; Ryu D; Holler C; Thompson BM
  • Granulins rescue inflammation, lysosome dysfunction, and neuropathology in a mouse model of progranulin deficiency.
    bioRxiv
    04/18/2023 Authors: Root J; Mendsaikhan A; Nandy S; Taylor G; Wang M; Araujo LT; Merino P; Ryu D; Holler C; Thompson BM
  • Regulation of TFEB nuclear localization by HSP90AA1 promotes autophagy and longevity.
    Autophagy Volume: 19 Page(s): 822 - 838
    03/01/2023 Authors: Yang S; Nie T; She H; Tao K; Lu F; Hu Y; Huang L; Zhu L; Feng D; He D
  • Proximity-based labeling reveals DNA damage-induced phosphorylation of fused in sarcoma (FUS) causes distinct changes in the FUS protein interactome.
    J Biol Chem Volume: 298 Page(s): 102135
    08/01/2022 Authors: Johnson MA; Nuckols TA; Merino P; Bagchi P; Nandy S; Root J; Taylor G; Seyfried NT; Kukar T
  • Lysosome dysfunction as a cause of neurodegenerative diseases: Lessons from frontotemporal dementia and amyotrophic lateral sclerosis.
    Neurobiol Dis Volume: 154 Page(s): 105360
    07/01/2021 Authors: Root J; Merino P; Nuckols A; Johnson M; Kukar T
  • Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
    Autophagy Volume: 17 Page(s): 1 - 382
    01/01/2021 Authors: Klionsky DJ; Abdel-Aziz AK; Abdelfatah S; Abdellatif M; Abdoli A; Abel S; Abeliovich H; Abildgaard MH; Abudu YP; Acevedo-Arozena A
  • Lysosomal Dysfunction and Other Pathomechanisms in FTLD: Evidence from Progranulin Genetics and Biology.
    Adv Exp Med Biol Volume: 1281 Page(s): 219 - 242
    01/01/2021 Authors: Zhou X; Kukar T; Rademakers R
  • Divergent FUS phosphorylation in primate and mouse cells following double-strand DNA damage.
    Neurobiol Dis Volume: 146 Page(s): 105085
    12/01/2020 Authors: Johnson MA; Deng Q; Taylor G; McEachin ZT; Chan AWS; Root J; Bassell GJ; Kukar T
  • Network analysis of the progranulin-deficient mouse brain proteome reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations.
    Acta Neuropathol Commun Volume: 8 Page(s): 163
    10/07/2020 Authors: Huang M; Modeste E; Dammer E; Merino P; Taylor G; Duong DM; Deng Q; Holler CJ; Gearing M; Dickson D
  • Chimeric Peptide Species Contribute to Divergent Dipeptide Repeat Pathology in c9ALS/FTD and SCA36.
    Neuron Volume: 107 Page(s): 292 - 305.e6
    07/22/2020 Authors: McEachin ZT; Gendron TF; Raj N; Garca-Murias M; Banerjee A; Purcell RH; Ward PJ; Todd TW; Merritt-Garza ME; Jansen-West K
  • Molecular Signatures of Neuroinflammation Induced by Synuclein Aggregates in Microglial Cells.
    Front Immunol Volume: 11 Page(s): 33
    01/01/2020 Authors: Sarkar S; Dammer EB; Malovic E; Olsen AL; Raza SA; Gao T; Xiao H; Oliver DL; Duong D; Joers V
  • TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD.
    Nat Neurosci Volume: 21 Page(s): 228 - 239
    02/01/2018 Authors: Chou C-C; Zhang Y; Umoh ME; Vaughan SW; Lorenzini I; Liu F; Sayegh M; Donlin-Asp PG; Chen YH; Duong DM
  • Short A peptides attenuate A42 toxicity in vivo.
    J Exp Med Volume: 215 Page(s): 283 - 301
    01/02/2018 Authors: Moore BD; Martin J; de Mena L; Sanchez J; Cruz PE; Ceballos-Diaz C; Ladd TB; Ran Y; Levites Y; Kukar TL
  • Disulfide bonds and disorder in granulin-3: An unusual handshake between structural stability and plasticity.
    Protein Sci Volume: 26 Page(s): 1759 - 1772
    09/01/2017 Authors: Ghag G; Holler CJ; Taylor G; Kukar TL; Uversky VN; Rangachari V
  • Intracellular Proteolysis of Progranulin Generates Stable, Lysosomal Granulins that Are Haploinsufficient in Patients with Frontotemporal Dementia Caused by GRN Mutations.
    eNeuro Volume: 4
    01/01/2017 Authors: Holler CJ; Taylor G; Deng Q; Kukar T
  • Lysosomal production of granulins: implications for the pathogenesis of neuronal ceroid lipofuscinosis and frontotemporal dementia
    Volume: 120 Page(s): S78 - S79
    01/01/2017 Authors: Kukar T; Holler CJ; Taylor G
  • Trehalose enhances progranulin expression in progranulin-deficient patient cells and mouse brain
    Volume: 138 Page(s): 249 - 249
    08/01/2016 Authors: Holler C; Taylor G; McEachin Z; Deng Q; Watkins W; Hudson K; Easley C; Hu W; Hales C; Rossoll W
  • Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia.
    Mol Neurodegener Volume: 11 Page(s): 46
    06/24/2016 Authors: Holler CJ; Taylor G; McEachin ZT; Deng Q; Watkins WJ; Hudson K; Easley CA; Hu WT; Hales CM; Rossoll W
  • FUS is phosphorylated by DNA-PK and accumulates in the cytoplasm after DNA damage.
    J Neurosci Volume: 34 Page(s): 7802 - 7813
    06/04/2014 Authors: Deng Q; Holler CJ; Taylor G; Hudson KF; Watkins W; Gearing M; Ito D; Murray ME; Dickson DW; Seyfried NT
  • Complex relationships between substrate sequence and sensitivity to alterations in -secretase processivity induced by -secretase modulators.
    Biochemistry Volume: 53 Page(s): 1947 - 1957
    04/01/2014 Authors: Jung JI; Ran Y; Cruz PE; Rosario AM; Ladd TB; Kukar TL; Koo EH; Felsenstein KM; Golde TE
  • Steroids as -secretase modulators.
    FASEB J Volume: 27 Page(s): 3775 - 3785
    09/01/2013 Authors: Jung JI; Ladd TB; Kukar T; Price AR; Moore BD; Koo EH; Golde TE; Felsenstein KM
  • Progranulin does not bind tumor necrosis factor (TNF) receptors and is not a direct regulator of TNF-dependent signaling or bioactivity in immune or neuronal cells.
    J Neurosci Volume: 33 Page(s): 9202 - 9213
    05/22/2013 Authors: Chen X; Chang J; Deng Q; Xu J; Nguyen TA; Martens LH; Cenik B; Taylor G; Hudson KF; Chung J
  • Expression of Fused in sarcoma mutations in mice recapitulates the neuropathology of FUS proteinopathies and provides insight into disease pathogenesis.
    Mol Neurodegener Volume: 7 Page(s): 53
    10/10/2012 Authors: Verbeeck C; Deng Q; Dejesus-Hernandez M; Taylor G; Ceballos-Diaz C; Kocerha J; Golde T; Das P; Rademakers R; Dickson DW
  • Transient pharmacologic lowering of A production prior to deposition results in sustained reduction of amyloid plaque pathology.
    Mol Neurodegener Volume: 7 Page(s): 39
    08/14/2012 Authors: Das P; Verbeeck C; Minter L; Chakrabarty P; Felsenstein K; Kukar T; Maharvi G; Fauq A; Osborne BA; Golde TE
  • Overlapping profiles of A peptides in the Alzheimer's disease and pathological aging brains.
    Alzheimers Res Ther Volume: 4 Page(s): 18
    05/23/2012 Authors: Moore BD; Chakrabarty P; Levites Y; Kukar TL; Baine A-M; Moroni T; Ladd TB; Das P; Dickson DW; Golde TE
  • Guidelines for the use and interpretation of assays for monitoring autophagy.
    Autophagy Volume: 8 Page(s): 445 - 544
    04/01/2012 Authors: Klionsky DJ; Abdalla FC; Abeliovich H; Abraham RT; Acevedo-Arozena A; Adeli K; Agholme L; Agnello M; Agostinis P; Aguirre-Ghiso JA
  • Lysine 624 of the amyloid precursor protein (APP) is a critical determinant of amyloid peptide length: support for a sequential model of -secretase intramembrane proteolysis and regulation by the amyloid precursor protein (APP) juxtamembrane region.
    J Biol Chem Volume: 286 Page(s): 39804 - 39812
    11/18/2011 Authors: Kukar TL; Ladd TB; Robertson P; Pintchovski SA; Moore B; Bann MA; Ren Z; Jansen-West K; Malphrus K; Eggert S
  • Substrate sequence influences -secretase modulator activity, role of the transmembrane domain of the amyloid precursor protein.
    J Biol Chem Volume: 286 Page(s): 39794 - 39803
    11/18/2011 Authors: Sagi SA; Lessard CB; Winden KD; Maruyama H; Koo JC; Weggen S; Kukar TL; Golde TE; Koo EH
  • An NSAID-like compound, FT-9, preferentially inhibits gamma-secretase cleavage of the amyloid precursor protein compared to its effect on amyloid precursor-like protein 1.
    Biochemistry Volume: 48 Page(s): 10894 - 10904
    11/24/2009 Authors: Sala Frigerio C; Kukar TL; Fauq A; Engel PC; Golde TE; Walsh DM
  • Medicine. Avoiding unintended toxicity.
    Science Volume: 324 Page(s): 603 - 604
    05/01/2009 Authors: Golde TE; Kukar TL
  • Selective modulation of the gamma cleavage of Alzheimer's disease amyloid precursor proteins
    Volume: 197 Page(s): 165 - 165
    07/15/2008 Authors: Frigerio CS; Kukar T; Osenkowski P; Wolfe MS; Golde T; Engel PC; Walsh DM
  • Independent generation of Abeta42 and Abeta38 peptide species by gamma-secretase.
    J Biol Chem Volume: 283 Page(s): 17049 - 17054
    06/20/2008 Authors: Czirr E; Cottrell BA; Leuchtenberger S; Kukar T; Ladd TB; Esselmann H; Paul S; Schubenel R; Torpey JW; Pietrzik CU
  • Substrate-targeting gamma-secretase modulators.
    Nature Volume: 453 Page(s): 925 - 929
    06/12/2008 Authors: Kukar TL; Ladd TB; Bann MA; Fraering PC; Narlawar R; Maharvi GM; Healy B; Chapman R; Welzel AT; Price RW
  • Possible mechanisms of action of NSAIDs and related compounds that modulate gamma-secretase cleavage.
    Curr Top Med Chem Volume: 8 Page(s): 47 - 53
    01/01/2008 Authors: Kukar T; Golde TE
  • Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice.
    BMC Neurosci Volume: 8 Page(s): 54
    07/24/2007 Authors: Kukar T; Prescott S; Eriksen JL; Holloway V; Murphy MP; Koo EH; Golde TE; Nicolle MM
  • Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase.
    FASEB J Volume: 20 Page(s): 1671 - 1679
    08/01/2006 Authors: Nyborg AC; Ladd TB; Jansen K; Kukar T; Golde TE
  • Inhibitors of Rho-kinase modulate amyloid-beta (Abeta) secretion but lack selectivity for Abeta42.
    J Neurochem Volume: 96 Page(s): 355 - 365
    01/01/2006 Authors: Leuchtenberger S; Kummer MP; Kukar T; Czirr E; Teusch N; Sagi SA; Berdeaux R; Pietrzik CU; Ladd TB; Golde TE
  • Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production.
    Nat Med Volume: 11 Page(s): 545 - 550
    05/01/2005 Authors: Kukar T; Murphy MP; Eriksen JL; Sagi SA; Weggen S; Smith TE; Ladd T; Khan MA; Kache R; Beard J
  • Structural insights and functional implications of choline acetyltransferase.
    J Struct Biol Volume: 148 Page(s): 226 - 235
    11/01/2004 Authors: Govindasamy L; Pedersen B; Lian W; Kukar T; Gu Y; Jin S; Agbandje-McKenna M; Wu D; McKenna R
  • Selective ABETA42 modifying agents: Effects on abeta deposition and behavior in TG2576 mice
    Volume: 25 Page(s): S64 - S64
    07/01/2004 Authors: Golde TE; Eriksen J; Nicolle M; Murphy MP; Kukar T; Monnier T; Prescott S; Wright S; Chevallier N; Sagi S
  • Compounds that raise A beta 42 provide insight into the mechanism of gamma-secretase cleavage modulation
    Volume: 25 Page(s): S567 - S567
    07/01/2004 Authors: Kukar T
  • Structural and mutational characterization of L-carnitine binding to human carnitine acetyltransferase.
    J Struct Biol Volume: 146 Page(s): 416 - 424
    06/01/2004 Authors: Govindasamy L; Kukar T; Lian W; Pedersen B; Gu Y; Agbandje-McKenna M; Jin S; McKenna R; Wu D
  • Crystallization and preliminary X-ray crystallographic studies on recombinant rat choline acetyltransferase.
    Acta Crystallogr D Biol Crystallogr Volume: 60 Page(s): 374 - 375
    02/01/2004 Authors: Lian W; Gu Y; Pedersen B; Kukar T; Govindasamy L; Agbandje-McKenna M; Jin S; McKenna R; Wu D
  • Structure of human carnitine acetyltransferase. Molecular basis for fatty acyl transfer.
    J Biol Chem Volume: 278 Page(s): 13159 - 13165
    04/11/2003 Authors: Wu D; Govindasamy L; Lian W; Gu Y; Kukar T; Agbandje-McKenna M; McKenna R
  • Crystallization and preliminary X-ray crystallographic studies on recombinant human carnitine acetyltransferase.
    Acta Crystallogr D Biol Crystallogr Volume: 58 Page(s): 1193 - 1194
    07/01/2002 Authors: Lian W; Govindasamy L; Gu Y; Kukar T; Agbandje-McKenna M; McKenna R; Wu D
  • Protein microarrays to detect protein-protein interactions using red and green fluorescent proteins.
    Anal Biochem Volume: 306 Page(s): 50 - 54
    07/01/2002 Authors: Kukar T; Eckenrode S; Gu Y; Lian W; Megginson M; She J-X; Wu D
  • Molecular cloning and characterization of the mouse and human TUSP gene, a novel member of the tubby superfamily.
    Gene Volume: 273 Page(s): 275 - 284
    08/08/2001 Authors: Li QZ; Wang CY; Shi JD; Ruan QG; Eckenrode S; Davoodi-Semiromi A; Kukar T; Gu Y; Lian W; Wu D
  • Molecular cloning and characterization of a novel mammalian endo-apyrase (LALP1).
    J Biol Chem Volume: 276 Page(s): 17474 - 17478
    05/18/2001 Authors: Shi JD; Kukar T; Wang CY; Li QZ; Cruz PE; Davoodi-Semiromi A; Yang P; Gu Y; Lian W; Wu DH
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