Publications

Dimitri Krainc, MD, PhD, the Aaron Montgomery Ward Professor

Elucidating Parkinson’s Disease

A study from the Krainc laboratory published in Nature showed that mitochondria and lysosomes form direct contacts, and recent work published in Nature showed that these contacts are disrupted in PD.

Dimitri Krainc MD, Ph.D. new strategy to treat Parkinson’s disease published in the journal Science

Northwestern Medicine scientists have identified a toxic cascade that leads to neuronal degeneration in patients with Parkinson’s disease (PD)

Interaction of Mitochondria and Lysosomes Key in Parkinson’s Disease

Northwestern Medicine scientists have identified the consequences of contact between the mitochondria and the lysosome in the axons and synapses of human neurons.

New Genetic Cause of Dystonia Revealed

The disorder causes involuntary muscle contraction and repetitive or twisting movements, and these findings broaden the horizon of potential therapies, according to Dimitri Krainc, MD, PhD, chair and the Aaron Montgomery Ward Professor of Neurology and co-senior author of the study.

Dimitri Krainc, NorthWestern Medicine elected to the Association of American Physicians (AAP)

Dimitri Krainc, MD, Ph.D Northwestern Medicine and the Aaron Montgomery Ward Professor of Neurology was elected to the Association of American Physicians (AAP)

Krainc to receive $9 Million, 8-year NIH Grant

Dimitri Krainc, MD, PhD, chair and the Aaron Montgomery Ward Professor of Neurology, has received a Research Program Award grant from the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH).

Northwestern Medicine scientists have discovered that two key cellular structures published in the journal Nature

For the first time, Northwestern Medicine scientists have discovered that two key cellular structures, mitochondria and lysosomes,

Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson’s Disease.

Domenighetti C, Sugier P-E, Sreelatha AAK, Schulte C, Grover S, Mohamed O, Portugal B, May P, Bobbili DR, Radivojkov-Blagojevic M, Lichtner P, Singleton AB, Hernandez DG, Edsall C, Mellick GD, Zimprich A, Pirker W, Rogaeva E, Lang AE, Koks S, Taba P, Lesage S, Brice A, Corvol J-C, Chartier-Harlin M-C, Mutez E, Brockmann K, Deutschländer AB, Hadjigeorgiou GM, Dardiotis E, Stefanis L, Simitsi AM, Valente EM, Petrucci S, Duga S, Straniero L, Zecchinelli A, Pezzoli G, Brighina L, Ferrarese C, Annesi G, Quattrone A, Gagliardi M, Matsuo H, Kawamura Y, Hattori N, Nishioka K, Chung SJ, Kim YJ, Kolber P, van de Warrenburg BP, Bloem BR, Aasly J, Toft M, Pihlstrøm L, Guedes LC, Ferreira JJ, Bardien S, Carr J, Tolosa E, Ezquerra M, Pastor P, Diez-Fairen M, Wirdefeldt K, Pedersen NL, Ran C, Belin AC, Puschmann A, Hellberg C, Clarke CE, Morrison KE, Tan M, Krainc D, Burbulla LF, Farrer MJ, Krüger R, Gasser T, Sharma M, Elbaz A, Comprehensive Unbiaised Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (Courage-PD) consortium

J Parkinsons Dis. 2022; 12(1): 267-282.

https://doi.org/10.3233/JPD-212851

PMID: 34633332
Evaluation of Strategies for Measuring Lysosomal Glucocerebrosidase Activity.

Ysselstein D, Young TJ, Nguyen M, Padmanabhan S, Hirst WD, Dzamko N, Krainc D

Mov Disord. 2021 Dec; 36(12): 2719-2730.

https://doi.org/10.1002/mds.28815

PMID: 34613624
Glucocerebrosidase dysfunction in neurodegenerative disease.

Brooker SM, Krainc D

Essays Biochem. 2021 Dec; 65(7): 873-883.

https://doi.org/10.1042/EBC20210018

PMID: 34528667
Identification of ASCL1 as a determinant for human iPSC-derived dopaminergic neurons.

Earley AM, Burbulla LF, Krainc D, Awatramani R

Sci Rep. 2021 Nov; 11(1): 22257-.

https://doi.org/10.1038/s41598-021-01366-4

PMID: 34782629
Heterozygous GBA D409V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice.

Johnson ME, Bergkvist L, Stetzik L, Steiner JA, Meyerdirk L, Schulz E, Wolfrum E, Luk KC, Wesson DW, Krainc D, Brundin P

Neurobiol Dis. 2021 Nov; 159: 105513-.

https://doi.org/10.1016/j.nbd.2021.105513

PMID: 34536552
Direct targeting of wild-type glucocerebrosidase by antipsychotic quetiapine improves pathogenic phenotypes in Parkinson’s disease models.

Burbulla LF, Zheng J, Song P, Jiang W, Johnson ME, Brundin P, Krainc D

JCI Insight. 2021 Oct; 6(19):

https://doi.org/10.1172/jci.insight.148649

PMID: 34622801
Replication assessment of NUS1 variants in Parkinson’s disease.

Bustos BI, Bandres-Ciga S, Gibbs JR, Krainc D, Mencacci NE, Gan-Or Z, Lubbe SJ, International Parkinson’s Disease Genomics Consortium (IPDGC)

Neurobiol Aging. 2021 May; 101: 300.e1-300.e3.

https://doi.org/10.1016/j.neurobiolaging.2020.11.007

PMID: 33309333
Biallelic variants in TSPOAP1, encoding the active-zone protein RIMBP1, cause autosomal recessive dystonia.

Mencacci NE, Brockmann MM, Dai J, Pajusalu S, Atasu B, Campos J, Pino G, Gonzalez-Latapi P, Patzke C, Schwake M, Tucci A, Pittman A, Simon-Sanchez J, Carvill GL, Balint B, Wiethoff S, Warner TT, Papandreou A, Soo A, Rein R, Kadastik-Eerme L, Puusepp S, Reinson K, Tomberg T, Hanagasi H, Gasser T, Bhatia KP, Kurian MA, Lohmann E, Õunap K, Rosenmund C, Südhof TC, Wood NW, Krainc D, Acuna C

J Clin Invest. 2021 Apr; 131(7):

https://doi.org/10.1172/JCI140625

PMID: 33539324
Modeling Brain Pathology of Niemann-Pick Disease Type C Using Patient-Derived Neurons.

Burbulla LF, Mc Donald JM, Valdez C, Gao F, Bigio EH, Krainc D

Mov Disord. 2021 Apr; 36(4): 1022-1027.

https://doi.org/10.1002/mds.28463

PMID: 33438272
MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia.

Meng L, Isohanni P, Shao Y, Graham BH, Hickey SE, Brooks S, Suomalainen A, Joset P, Steindl K, Rauch A, Hackenberg A, High FA, Armstrong-Javors A, Mencacci NE, Gonzàlez-Latapi P, Kamel WA, Al-Hashel JY, Bustos BI, Hernandez AV, Krainc D, Lubbe SJ, Van Esch H, De Luca C, Ballon K, Ravelli C, Burglen L, Qebibo L, Calame DG, Mitani T, Marafi D, Pehlivan D, Saadi NW, Sahin Y, Maroofian R, Efthymiou S, Houlden H, Maqbool S, Rahman F, Gu S, Posey JE, Lupski JR, Hunter JV, Wangler MF, Carroll CJ, Yang Y

Ann Neurol. 2021 Apr; 89(4): 828-833.

https://doi.org/10.1002/ana.26019

PMID: 33443317
Dysregulation of mitochondria-lysosome contacts by GBA1 dysfunction in dopaminergic neuronal models of Parkinson’s disease.

Kim S, Wong YC, Gao F, Krainc D

Nat Commun. 2021 Mar; 12(1): 1807-.

https://doi.org/10.1038/s41467-021-22113-3

PMID: 33753743
Assessing the relationship between monoallelic PRKN mutations and Parkinson’s risk.

Lubbe SJ, Bustos BI, Hu J, Krainc D, Joseph T, Hehir J, Tan M, Zhang W, Escott-Price V, Williams NM, Blauwendraat C, Singleton AB, Morris HR, for International Parkinson’s Disease Genomics Consortium (IPDGC)

Hum Mol Genet. 2021 Mar; 30(1): 78-86.

https://doi.org/10.1093/hmg/ddaa273

PMID: 33448283
Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy.

Charif M, Wong YC, Kim S, Guichet A, Vignal C, Zanlonghi X, Bensaid P, Procaccio V, Bonneau D, Amati-Bonneau P, Reynier P, Krainc D, Lenaers G

Mol Neurodegener. 2021 Feb; 16(1): 12-.

https://doi.org/10.1186/s13024-021-00431-w

PMID: 33632269
Astrocytes Protect Human Dopaminergic Neurons from α-Synuclein Accumulation and Propagation.

Tsunemi T, Ishiguro Y, Yoroisaka A, Valdez C, Miyamoto K, Ishikawa K, Saiki S, Akamatsu W, Hattori N, Krainc D

J Neurosci. 2020 Nov; 40(45): 8618-8628.

https://doi.org/10.1523/JNEUROSCI.0954-20.2020

PMID: 33046546
A patient-based model of RNA mis-splicing uncovers treatment targets in Parkinson’s disease.

Boussaad I, Obermaier CD, Hanss Z, Bobbili DR, Bolognin S, Glaab E, Wolynska K, Weisschuh N, De Conti L, May C, Giesert F, Grossmann D, Lambert A, Kirchen S, Biryukov M, Burbulla LF, Massart F, Bohler J, Cruciani G, Schmid B, Kurz-Drexler A, May P, Duga S, Klein C, Schwamborn JC, Marcus K, Woitalla D, Vogt Weisenhorn DM, Wurst W, Baralle M, Krainc D, Gasser T, Wissinger B, Krüger R

Sci Transl Med. 2020 Sep; 12(560):

https://doi.org/10.1126/scitranslmed.aau3960

PMID: 32908004
Mitochondria-lysosome contacts regulate mitochondrial Ca2+ dynamics via lysosomal TRPML1.

Peng W, Wong YC, Krainc D

Proc Natl Acad Sci U S A. 2020 Aug; 117(32): 19266-19275.

https://doi.org/10.1073/pnas.2003236117

PMID: 32703809
Organoid and pluripotent stem cells in Parkinson’s disease modeling: an expert view on their value to drug discovery.

Marotta N, Kim S, Krainc D

Expert Opin Drug Discov. 2020 Apr; 15(4): 427-441.

https://doi.org/10.1080/17460441.2020.1703671

PMID: 31899983
Progranulin mutations result in impaired processing of prosaposin and reduced glucocerebrosidase activity.

Valdez C, Ysselstein D, Young TJ, Zheng J, Krainc D

Hum Mol Genet. 2020 Mar; 29(5): 716-726.

https://doi.org/10.1093/hmg/ddz229

PMID: 31600775
Author Correction: Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain.

Graves SM, Xie Z, Stout KA, Zampese E, Burbulla LF, Shih JC, Kondapalli J, Patriarchi T, Tian L, Brichta L, Greengard P, Krainc D, Schumacker PT, Surmeier DJ

Nat Neurosci. 2020 Feb; 23(2): 293-.

https://doi.org/10.1038/s41593-019-0583-0

PMID: 31911656
Gelator length precisely tunes supramolecular hydrogel stiffness and neuronal phenotype in 3D culture.

Godbe JM, Freeman R, Burbulla LF, Lewis J, Krainc D, Stupp SI

ACS Biomater Sci Eng. 2020 Feb; 6(2): 1196-1207.

https://doi.org/10.1021/acsbiomaterials.9b01585

PMID: 33094153 ISSN: 2373-9878
Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain.

Graves SM, Xie Z, Stout KA, Zampese E, Burbulla LF, Shih JC, Kondapalli J, Patriarchi T, Tian L, Brichta L, Greengard P, Krainc D, Schumacker PT, Surmeier DJ

Nat Neurosci. 2020 Jan; 23(1): 15-20.

https://doi.org/10.1038/s41593-019-0556-3

PMID: 31844313
The Convergence of Alpha-Synuclein, Mitochondrial, and Lysosomal Pathways in Vulnerability of Midbrain Dopaminergic Neurons in Parkinson’s Disease.

Minakaki G, Krainc D, Burbulla LF

Front Cell Dev Biol. 2020; 8: 580634-.

https://doi.org/10.3389/fcell.2020.580634

PMID: 33381501 ISSN: 2296-634X
The role of dopamine in the pathogenesis of GBA1-linked Parkinson’s disease.

Burbulla LF, Krainc D

Neurobiol Dis. 2019 Dec; 132: 104545-.

https://doi.org/10.1016/j.nbd.2019.104545

PMID: 31351996
LRRK2 kinase activity regulates lysosomal glucocerebrosidase in neurons derived from Parkinson’s disease patients.

Ysselstein D, Nguyen M, Young TJ, Severino A, Schwake M, Merchant K, Krainc D

Nat Commun. 2019 Dec; 10(1): 5570-.

https://doi.org/10.1038/s41467-019-13413-w

PMID: 31804465
A modulator of wild-type glucocerebrosidase improves pathogenic phenotypes in dopaminergic neuronal models of Parkinson’s disease.

Burbulla LF, Jeon S, Zheng J, Song P, Silverman RB, Krainc D

Sci Transl Med. 2019 Oct; 11(514):

https://doi.org/10.1126/scitranslmed.aau6870

PMID: 31619543
Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?

Wong YC, Luk K, Purtell K, Burke Nanni S, Stoessl AJ, Trudeau L-E, Yue Z, Krainc D, Oertel W, Obeso JA, Volpicelli-Daley LA

Mov Disord. 2019 Oct; 34(10): 1406-1422.

https://doi.org/10.1002/mds.27823

PMID: 31483900
Lysosomal Regulation of Inter-mitochondrial Contact Fate and Motility in Charcot-Marie-Tooth Type 2.

Wong YC, Peng W, Krainc D

Dev Cell. 2019 Aug; 50(3): 339-354.e4.

https://doi.org/10.1016/j.devcel.2019.05.033

PMID: 31231042
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration.

Peng W, Minakaki G, Nguyen M, Krainc D

Neurotherapeutics. 2019 Jul; 16(3): 611-634.

https://doi.org/10.1007/s13311-019-00742-3

PMID: 31183763
Increased Lysosomal Exocytosis Induced by Lysosomal Ca2+ Channel Agonists Protects Human Dopaminergic Neurons from α-Synuclein Toxicity.

Tsunemi T, Perez-Rosello T, Ishiguro Y, Yoroisaka A, Jeon S, Hamada K, Rammonhan M, Wong YC, Xie Z, Akamatsu W, Mazzulli JR, Surmeier DJ, Hattori N, Krainc D

J Neurosci. 2019 Jul; 39(29): 5760-5772.

https://doi.org/10.1523/JNEUROSCI.3085-18.2019

PMID: 31097622
Correction to: Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration.

Peng W, Minakaki G, Nguyen M, Krainc D

Neurotherapeutics. 2019 Jul; 16(3): 920-921.

https://doi.org/10.1007/s13311-019-00756-x

PMID: 31342409
Regulation and Function of Mitochondria-Lysosome Membrane Contact Sites in Cellular Homeostasis.

Wong YC, Kim S, Peng W, Krainc D

Trends Cell Biol. 2019 Jun; 29(6): 500-513.

https://doi.org/10.1016/j.tcb.2019.02.004

PMID: 30898429
Emerging links between pediatric lysosomal storage diseases and adult parkinsonism.

Ysselstein D, Shulman JM, Krainc D

Mov Disord. 2019 May; 34(5): 614-624.

https://doi.org/10.1002/mds.27631

PMID: 30726573
Correction to Conversion of Quinazoline Modulators from Inhibitors to Activators of β-Glucocerebrosidase.

Zheng J, Jeon S, Jiang W, Burbulla LF, Ysselstein D, Oevel K, Krainc D, Silverman RB

J Med Chem. 2019 Mar; 62(5): 2850-.

https://doi.org/10.1021/acs.jmedchem.9b00284

PMID: 30793892
Corrigendum.

Brain. 2019 Mar; 142(3): e10-.

https://doi.org/10.1093/brain/awy316

PMID: 30561516
Conversion of Quinazoline Modulators from Inhibitors to Activators of β-Glucocerebrosidase.

Zheng J, Jeon S, Jiang W, Burbulla LF, Ysselstein D, Oevel K, Krainc D, Silverman RB

J Med Chem. 2019 Feb; 62(3): 1218-1230.

https://doi.org/10.1021/acs.jmedchem.8b01294

PMID: 30645117
Synaptic, Mitochondrial, and Lysosomal Dysfunction in Parkinson’s Disease.

Nguyen M, Wong YC, Ysselstein D, Severino A, Krainc D

Trends Neurosci. 2019 Feb; 42(2): 140-149.

https://doi.org/10.1016/j.tins.2018.11.001

PMID: 30509690
Fluctuations in cell density alter protein markers of multiple cellular compartments, confounding experimental outcomes.

Trajkovic K, Valdez C, Ysselstein D, Krainc D

PLoS One. 2019; 14(2): e0211727-.

https://doi.org/10.1371/journal.pone.0211727

PMID: 30716115
Novel Approach to Tracking Mutant Huntingtin in Biosamples.

Trajkovic K, Krainc D

Trends Mol Med. 2018 Dec; 24(12): 978-981.

https://doi.org/10.1016/j.molmed.2018.10.002

PMID: 30509361
Untangling alpha synuclein fibrils by graphene quantum dots.

Ysselstein D, Krainc D

Mov Disord. 2018 Nov; 33(11): 1673-.

https://doi.org/10.1002/mds.27511

PMID: 30485906
Iron overload is accompanied by mitochondrial and lysosomal dysfunction in WDR45 mutant cells.

Seibler P, Burbulla LF, Dulovic M, Zittel S, Heine J, Schmidt T, Rudolph F, Westenberger A, Rakovic A, Münchau A, Krainc D, Klein C

Brain. 2018 Oct; 141(10): 3052-3064.

https://doi.org/10.1093/brain/awy230

PMID: 30169597
Molecular mechanisms of α-synuclein and GBA1 in Parkinson’s disease.

Stojkovska I, Krainc D, Mazzulli JR

Cell Tissue Res. 2018 Jul; 373(1): 51-60.

https://doi.org/10.1007/s00441-017-2704-y

PMID: 29064079
Acid ceramidase inhibition ameliorates α-synuclein accumulation upon loss of GBA1 function.

Kim MJ, Jeon S, Burbulla LF, Krainc D

Hum Mol Genet. 2018 Jun; 27(11): 1972-1988.

https://doi.org/10.1093/hmg/ddy105

PMID: 29579237
Recessive mutations in VPS13D cause childhood onset movement disorders.

Gauthier J, Meijer IA, Lessel D, Mencacci NE, Krainc D, Hempel M, Tsiakas K, Prokisch H, Rossignol E, Helm MH, Rodan LH, Karamchandani J, Carecchio M, Lubbe SJ, Telegrafi A, Henderson LB, Lorenzo K, Wallace SE, Glass IA, Hamdan FF, Michaud JL, Rouleau GA, Campeau PM

Ann Neurol. 2018 Jun; 83(6): 1089-1095.

https://doi.org/10.1002/ana.25204

PMID: 29518281
β-Glucocerebrosidase Modulators Promote Dimerization of β-Glucocerebrosidase and Reveal an Allosteric Binding Site.

Zheng J, Chen L, Skinner OS, Ysselstein D, Remis J, Lansbury P, Skerlj R, Mrosek M, Heunisch U, Krapp S, Charrow J, Schwake M, Kelleher NL, Silverman RB, Krainc D

J Am Chem Soc. 2018 May; 140(18): 5914-5924.

https://doi.org/10.1021/jacs.7b13003

PMID: 29676907
LRRK2 phosphorylation of auxilin mediates synaptic defects in dopaminergic neurons from patients with Parkinson’s disease.

Nguyen M, Krainc D

Proc Natl Acad Sci U S A. 2018 May; 115(21): 5576-5581.

https://doi.org/10.1073/pnas.1717590115

PMID: 29735704
Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis.

Wong YC, Ysselstein D, Krainc D

Nature. 2018 Feb; 554(7692): 382-386.

https://doi.org/10.1038/nature25486

PMID: 29364868
High priority publications on Parkinson’s disease in 2017.

Simuni T, Krainc D

Lancet Neurol. 2018 Jan; 17(1): 8-10.

https://doi.org/10.1016/S1474-4422(17)30416-7

PMID: 29263010
BACE1-cleavage of Sez6 and Sez6L is elevated in Niemann-Pick type C disease mouse brains.

Causevic M, Dominko K, Malnar M, Vidatic L, Cermak S, Pigoni M, Kuhn P-H, Colombo A, Havas D, Flunkert S, McDonald J, Gunnersen JM, Hutter-Paier B, Tahirovic S, Windisch M, Krainc D, Lichtenthaler SF, Hecimovic S

PLoS One. 2018; 13(7): e0200344-.

https://doi.org/10.1371/journal.pone.0200344

PMID: 29979789
Functional assays for the assessment of the pathogenicity of variants of GOSR2, an ER-to-Golgi SNARE involved in progressive myoclonus epilepsies.

Völker JM, Dergai M, Abriata LA, Mingard Y, Ysselstein D, Krainc D, Dal Peraro M, Fischer von Mollard G, Fasshauer D, Koliwer J, Schwake M

Dis Model Mech. 2017 Dec; 10(12): 1391-1398.

https://doi.org/10.1242/dmm.029132

PMID: 28982678
Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein.

Al-Ramahi I, Giridharan SSP, Chen Y-C, Patnaik S, Safren N, Hasegawa J, de Haro M, Wagner Gee AK, Titus SA, Jeong H, Clarke J, Krainc D, Zheng W, Irvine RF, Barmada S, Ferrer M, Southall N, Weisman LS, Botas J, Marugan JJ

Elife. 2017 Dec; 6:

https://doi.org/10.7554/eLife.29123

PMID: 29256861
Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies.

Conrad KS, Cheng T-W, Ysselstein D, Heybrock S, Hoth LR, Chrunyk BA, Am Ende CW, Krainc D, Schwake M, Saftig P, Liu S, Qiu X, Ehlers MD

Nat Commun. 2017 Dec; 8(1): 1908-.

https://doi.org/10.1038/s41467-017-02044-8

PMID: 29199275
Progranulin-mediated deficiency of cathepsin D results in FTD and NCL-like phenotypes in neurons derived from FTD patients.

Valdez C, Wong YC, Schwake M, Bu G, Wszolek ZK, Krainc D

Hum Mol Genet. 2017 Dec; 26(24): 4861-4872.

https://doi.org/10.1093/hmg/ddx364

PMID: 29036611
A PDE10A de novo mutation causes childhood-onset chorea with diurnal fluctuations.

Esposito S, Carecchio M, Tonduti D, Saletti V, Panteghini C, Chiapparini L, Zorzi G, Pantaleoni C, Garavaglia B, Krainc D, Lubbe SJ, Nardocci N, Mencacci NE

Mov Disord. 2017 Nov; 32(11): 1646-1647.

https://doi.org/10.1002/mds.27175

PMID: 28949041
Analysis of blood-based gene expression in idiopathic Parkinson disease.

Shamir R, Klein C, Amar D, Vollstedt E-J, Bonin M, Usenovic M, Wong YC, Maver A, Poths S, Safer H, Corvol J-C, Lesage S, Lavi O, Deuschl G, Kuhlenbaeumer G, Pawlack H, Ulitsky I, Kasten M, Riess O, Brice A, Peterlin B, Krainc D

Neurology. 2017 Oct; 89(16): 1676-1683.

https://doi.org/10.1212/WNL.0000000000004516

PMID: 28916538
Mutant Huntingtin Is Secreted via a Late Endosomal/Lysosomal Unconventional Secretory Pathway.

Trajkovic K, Jeong H, Krainc D

J Neurosci. 2017 Sep; 37(37): 9000-9012.

https://doi.org/10.1523/JNEUROSCI.0118-17.2017

PMID: 28821645
Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease.

Burbulla LF, Song P, Mazzulli JR, Zampese E, Wong YC, Jeon S, Santos DP, Blanz J, Obermaier CD, Strojny C, Savas JN, Kiskinis E, Zhuang X, Krüger R, Surmeier DJ, Krainc D

Science. 2017 Sep; 357(6357): 1255-1261.

https://doi.org/10.1126/science.aam9080

PMID: 28882997
α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies.

Wong YC, Krainc D

Nat Med. 2017 Feb; 23(2): 1-13.

https://doi.org/10.1038/nm.4269

PMID: 28170377
The Parkinson’s disease-linked protein TMEM230 is required for Rab8a-mediated secretory vesicle trafficking and retromer trafficking.

Kim MJ, Deng H-X, Wong YC, Siddique T, Krainc D

Hum Mol Genet. 2017 Feb; 26(4): 729-741.

https://doi.org/10.1093/hmg/ddw413

PMID: 28115417
Functional Impairment in Miro Degradation and Mitophagy Is a Shared Feature in Familial and Sporadic Parkinson’s Disease.

Hsieh C-H, Shaltouki A, Gonzalez AE, Bettencourt da Cruz A, Burbulla LF, St Lawrence E, Schüle B, Krainc D, Palmer TD, Wang X

Cell Stem Cell. 2016 Dec; 19(6): 709-724.

https://doi.org/10.1016/j.stem.2016.08.002

PMID: 27618216
Lysosomal trafficking defects link Parkinson’s disease with Gaucher’s disease.

Wong YC, Krainc D

Mov Disord. 2016 Nov; 31(11): 1610-1618.

https://doi.org/10.1002/mds.26802

PMID: 27619775
Parkin and PINK1 Patient iPSC-Derived Midbrain Dopamine Neurons Exhibit Mitochondrial Dysfunction and α-Synuclein Accumulation.

Chung SY, Kishinevsky S, Mazzulli JR, Graziotto J, Mrejeru A, Mosharov EV, Puspita L, Valiulahi P, Sulzer D, Milner TA, Taldone T, Krainc D, Studer L, Shim J-W

Stem Cell Reports. 2016 Oct; 7(4): 664-677.

https://doi.org/10.1016/j.stemcr.2016.08.012

PMID: 27641647
Design and Synthesis of Potent Quinazolines as Selective β-Glucocerebrosidase Modulators.

Zheng J, Chen L, Schwake M, Silverman RB, Krainc D

J Med Chem. 2016 Sep; 59(18): 8508-8520.

https://doi.org/10.1021/acs.jmedchem.6b00930

PMID: 27598312
Challenges to neurology residency education in today’s health care environment.

Bega D, Krainc D

Ann Neurol. 2016 Sep; 80(3): 315-320.

https://doi.org/10.1002/ana.24729

PMID: 27422739
Micropatterning Facilitates the Long-Term Growth and Analysis of iPSC-Derived Individual Human Neurons and Neuronal Networks.

Burbulla LF, Beaumont KG, Mrksich M, Krainc D

Adv Healthc Mater. 2016 Aug; 5(15): 1894-1903.

https://doi.org/10.1002/adhm.201500900

PMID: 27108930
Evidence of TAF1 dysfunction in peripheral models of X-linked dystonia-parkinsonism.

Domingo A, Amar D, Grütz K, Lee LV, Rosales R, Brüggemann N, Jamora RD, Cutiongco-Dela Paz E, Rolfs A, Dressler D, Walter U, Krainc D, Lohmann K, Shamir R, Klein C, Westenberger A

Cell Mol Life Sci. 2016 Aug; 73(16): 3205-3215.

https://doi.org/10.1007/s00018-016-2159-4

PMID: 26879577
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Adv Healthc Mater. 2016 Aug; 5(15): 1893-.

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Nat Genet. 2016 Jul; 48(7): 733-739.

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Mazzulli JR, Zunke F, Tsunemi T, Toker NJ, Jeon S, Burbulla LF, Patnaik S, Sidransky E, Marugan JJ, Sue CM, Krainc D

J Neurosci. 2016 Jul; 36(29): 7693-7706.

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Proc Natl Acad Sci U S A. 2016 Apr; 113(14): 3791-3796.

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Proc Natl Acad Sci U S A. 2016 Feb; 113(7): 1931-1936.

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Anal Chem. 2016 Feb; 88(4): 2399-2405.

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J Neurosci. 2016 Feb; 36(8): 2425-2437.

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J Neurosci. 2014 Nov; 34(46): 15281-15287.

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J Lipid Res. 2014 Oct; 55(10): 1996-2003.

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Proc Natl Acad Sci U S A. 2014 Oct; 111(43): 15573-15578.

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Cell Metab. 2014 Jul; 20(1): 145-157.

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Hum Mol Genet. 2014 Jun; 23(11): 2791-2801.

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JAMA. 2014 Feb; 311(6): 617-618.

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Cell Stem Cell. 2013 Dec; 13(6): 691-705.

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Proc Natl Acad Sci U S A. 2013 Aug; 110(32): E3027-E3036.

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Hum Mol Genet. 2013 May; 22(10): 2067-2082.

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Neurobiol Dis. 2013 Feb; 50: 127-134.

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Eur J Neurol. 2013 Feb; 20(2): 402-405.

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Pharmacological upregulation of PGC1α in oligodendrocytes: implications for Huntington’s Disease.

Xiang Z, Krainc D

J Huntingtons Dis. 2013; 2(1): 101-105.

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JAMA Neurology. 2013 Jan; 70(6): 686-688.

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J Biol Chem. 2013 Jan; 288(4): 2223-2237.

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Nature. 2012 Oct; 490(7419): 187-191.

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Hum Mol Genet. 2012 Sep; 21(17): 3785-3794.

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J Neurosci. 2012 Mar; 32(12): 4240-4246.

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Nat Med. 2011 Dec; 18(1): 159-165.

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Cell. 2011 Jul; 146(1): 37-52.

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PMID: 21715619
Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.

Cao K, Graziotto JJ, Blair CD, Mazzulli JR, Erdos MR, Krainc D, Collins FS

Sci Transl Med. 2011 Jun; 3(89): 89ra58-.

https://doi.org/10.1126/scitranslmed.3002346

PMID: 21715679
Translational research in neurology and neuroscience 2011: movement disorders.

Klein C, Krainc D, Schlossmacher MG, Lang AE

Arch Neurol. 2011 Jun; 68(6): 709-716.

https://doi.org/10.1001/archneurol.2011.11

PMID: 21320985
Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells.

Seibler P, Graziotto J, Jeong H, Simunovic F, Klein C, Krainc D

J Neurosci. 2011 Apr; 31(16): 5970-5976.

https://doi.org/10.1523/JNEUROSCI.4441-10.2011

PMID: 21508222
Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors.

Kegel KB, Sapp E, Alexander J, Reeves P, Bleckmann D, Sobin L, Masso N, Valencia A, Jeong H, Krainc D, Palacino J, Curtis D, Kuhn R, Betschart C, Sena-Esteves M, Aronin N, Paganetti P, Difiglia M

Mol Neurodegener. 2010 Dec; 5: 58-.

https://doi.org/10.1186/1750-1326-5-58

PMID: 21156064
Clearance of mutant proteins as a therapeutic target in neurodegenerative diseases.

Krainc D

Arch Neurol. 2010 Apr; 67(4): 388-392.

https://doi.org/10.1001/archneurol.2010.40

PMID: 20385902
The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy.

Filimonenko M, Isakson P, Finley KD, Anderson M, Jeong H, Melia TJ, Bartlett BJ, Myers KM, Birkeland HCG, Lamark T, Krainc D, Brech A, Stenmark H, Simonsen A, Yamamoto A

Mol Cell. 2010 Apr; 38(2): 265-279.

https://doi.org/10.1016/j.molcel.2010.04.007

PMID: 20417604
Distinct region-specific alpha-synuclein oligomers in A53T transgenic mice: implications for neurodegeneration.

Tsika E, Moysidou M, Guo J, Cushman M, Gannon P, Sandaltzopoulos R, Giasson BI, Krainc D, Ischiropoulos H, Mazzulli JR

J Neurosci. 2010 Mar; 30(9): 3409-3418.

https://doi.org/10.1523/JNEUROSCI.4977-09.2010

PMID: 20203200
Huntington’s disease: tagged for clearance.

Krainc D

Nat Med. 2010 Jan; 16(1): 32-33.

https://doi.org/10.1038/nm0110-32

PMID: 20057421
Gene expression changes in blood as a putative biomarker for Huntington’s disease.

Lovrecic L, Kastrin A, Kobal J, Pirtosek Z, Krainc D, Peterlin B

Mov Disord. 2009 Nov; 24(15): 2277-2281.

https://doi.org/10.1002/mds.22477

PMID: 19844910
Genome-wide expression analysis of peripheral blood identifies candidate biomarkers for schizophrenia.

Kuzman MR, Medved V, Terzic J, Krainc D

J Psychiatr Res. 2009 Sep; 43(13): 1073-1077.

https://doi.org/10.1016/j.jpsychires.2009.03.005

PMID: 19358997
Acetylation targets mutant huntingtin to autophagosomes for degradation.

Jeong H, Then F, Melia TJ, Mazzulli JR, Cui L, Savas JN, Voisine C, Paganetti P, Tanese N, Hart AC, Yamamoto A, Krainc D

Cell. 2009 Apr; 137(1): 60-72.

https://doi.org/10.1016/j.cell.2009.03.018

PMID: 19345187
Huntington’s disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies.

Savas JN, Makusky A, Ottosen S, Baillat D, Then F, Krainc D, Shiekhattar R, Markey SP, Tanese N

Proc Natl Acad Sci U S A. 2008 Aug; 105(31): 10820-10825.

https://doi.org/10.1073/pnas.0800658105

PMID: 18669659
Sodium phenylbutyrate in Huntington’s disease: a dose-finding study.

Hogarth P, Lovrecic L, Krainc D

Mov Disord. 2007 Oct; 22(13): 1962-1964.

https://doi.org/10.1002/mds.21632

PMID: 17702032 ISSN: 0885-3185
Thermoregulatory and metabolic defects in Huntington’s disease transgenic mice implicate PGC-1alpha in Huntington’s disease neurodegeneration.

Weydt P, Pineda VV, Torrence AE, Libby RT, Satterfield TF, Lazarowski ER, Gilbert ML, Morton GJ, Bammler TK, Strand AD, Cui L, Beyer RP, Easley CN, Smith AC, Krainc D, Luquet S, Sweet IR, Schwartz MW, La Spada AR

Cell Metab. 2006 Nov; 4(5): 349-362.

https://doi.org/10.1016/j.cmet.2006.10.004

PMID: 17055784 ISSN: 1550-4131
Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration.

Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D

Cell. 2006 Oct; 127(1): 59-69.

https://doi.org/10.1016/j.cell.2006.09.015

PMID: 17018277 ISSN: 0092-8674
Decreased association of the transcription factor Sp1 with genes downregulated in Huntington’s disease.

Chen-Plotkin AS, Sadri-Vakili G, Yohrling GJ, Braveman MW, Benn CL, Glajch KE, DiRocco DP, Farrell LA, Krainc D, Gines S, MacDonald ME, Cha J-HJ

Neurobiol Dis. 2006 May; 22(2): 233-241.

https://doi.org/10.1016/j.nbd.2005.11.001

PMID: 16442295 ISSN: 0969-9961
In vitro analysis of huntingtin-mediated transcriptional repression reveals multiple transcription factor targets.

Zhai W, Jeong H, Cui L, Krainc D, Tjian R

Cell. 2005 Dec; 123(7): 1241-1253.

https://doi.org/10.1016/j.cell.2005.10.030

PMID: 16377565 ISSN: 0092-8674
Genome-wide expression profiling of human blood reveals biomarkers for Huntington’s disease.

Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV, Krainc D

Proc Natl Acad Sci U S A. 2005 Aug; 102(31): 11023-11028.

https://doi.org/10.1073/pnas.0504921102

PMID: 16043692 ISSN: 0027-8424
Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice.

Lin J, Wu P-H, Tarr PT, Lindenberg KS, St-Pierre J, Zhang C-Y, Mootha VK, Jäger S, Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC, Rohas LM, Zavacki AM, Cinti S, Shulman GI, Lowell BB, Krainc D, Spiegelman BM

Cell. 2004 Oct; 119(1): 121-135.

https://doi.org/10.1016/j.cell.2004.09.013

PMID: 15454086 ISSN: 0092-8674
Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain.

Luthi-Carter R, Hanson SA, Strand AD, Bergstrom DA, Chun W, Peters NL, Woods AM, Chan EY, Kooperberg C, Krainc D, Young AB, Tapscott SJ, Olson JM

Hum Mol Genet. 2002 Aug; 11(17): 1911-1926.

https://doi.org/10.1093/hmg/11.17.1911

PMID: 12165554 ISSN: 0964-6906
Sp1 and TAFII130 transcriptional activity disrupted in early Huntington’s disease.

Dunah AW, Jeong H, Griffin A, Kim Y-M, Standaert DG, Hersch SM, Mouradian MM, Young AB, Tanese N, Krainc D

Science. 2002 Jun; 296(5576): 2238-2243.

https://doi.org/10.1126/science.1072613

PMID: 11988536
Targeted gene repair and its application to neurodegenerative disorders.

Parekh-Olmedo H, Krainc D, Kmiec EB

Neuron. 2002 Feb; 33(4): 495-498.

https://doi.org/10.1016/s0896-6273(02)00594-9

PMID: 11856524 ISSN: 0896-6273
Antiapoptotic role of the p38 mitogen-activated protein kinase-myocyte enhancer factor 2 transcription factor pathway during neuronal differentiation.

Okamoto S, Krainc D, Sherman K, Lipton SA

Proc Natl Acad Sci U S A. 2000 Jun; 97(13): 7561-7566.

https://doi.org/10.1073/pnas.130502697

PMID: 10852968 ISSN: 0027-8424
Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1.

Krainc D, Bai G, Okamoto S, Carles M, Kusiak JW, Brent RN, Lipton SA

J Biol Chem. 1998 Oct; 273(40): 26218-26224.

https://doi.org/10.1074/jbc.273.40.26218

PMID: 9748305 ISSN: 0021-9258
Use of a two-hybrid system to investigate molecular interactions of GAP-43.

Chao S, Benowitz LI, Krainc D, Irwin N

Brain Res Mol Brain Res. 1996 Sep; 40(2): 195-202.

https://doi.org/10.1016/0169-328x(96)00049-6

PMID: 8872303 ISSN: 0169-328X
Identification of ArgBP1, an Arg protein tyrosine kinase binding protein that is the human homologue of a CNS-specific Xenopus gene.

Wang B, Mysliwiec T, Krainc D, Jensen RA, Sonoda G, Testa JR, Golemis EA, Kruh GD

Oncogene. 1996 May; 12(9): 1921-1929.

PMID: 8649853 ISSN: 0950-9232
Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved.

Krainc D, Haas M, Ward DC, Lipton SA, Bruns G, Leifer D

Genomics. 1995 Oct; 29(3): 809-811.

https://doi.org/10.1006/geno.1995.9927

PMID: 8575784 ISSN: 0888-7543
Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures.

Bonfoco E, Krainc D, Ankarcrona M, Nicotera P, Lipton SA

Proc Natl Acad Sci U S A. 1995 Aug; 92(16): 7162-7166.

https://doi.org/10.1073/pnas.92.16.7162

PMID: 7638161 ISSN: 0027-8424
hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors.

McDermott JC, Cardoso MC, Yu YT, Andres V, Leifer D, Krainc D, Lipton SA, Nadal-Ginard B

Mol Cell Biol. 1993 Apr; 13(4): 2564-2577.

https://doi.org/10.1128/mcb.13.4.2564-2577.1993

PMID: 8455629 ISSN: 0270-7306
MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex.

Leifer D, Krainc D, Yu YT, McDermott J, Breitbart RE, Heng J, Neve RL, Kosofsky B, Nadal-Ginard B, Lipton SA

Proc Natl Acad Sci U S A. 1993 Feb; 90(4): 1546-1550.

https://doi.org/10.1073/pnas.90.4.1546

PMID: 7679508 ISSN: 0027-8424

Books and Book Chapters

Lysosomal Proteins as a Therapeutic Target in Neurodegeneration.

Mc Donald JM, Krainc D

2017 Jan; 68: 445-458.

https://doi.org/10.1146/annurev-med-050715-104432

PMID: 28099085
Transcriptional Abnormalities in Huntington’s Disease

Krainc D

Transcription Factors in the Nervous System: Development, Brain Function, and Diseases. 2006 May; 417-440.

https://doi.org/10.1002/3527608036.ch20

ISBN: 9783527312856

Elucidating Parkinson’s Disease
Recent advances from Northwestern investigators have powered a new, deeper understanding of Parkinson’s disease that could pave the way to a disease-modifying treatment.
2021 Year in Review
Feinberg experienced a year of exceptional growth, perseverance, and collaboration in 2021, from honors and awards to unprecedented research discoveries.
Wong Honored with NIH New Innovator Award
Yvette Wong, PhD, assistant professor in the Ken and Ruth Davee Department of Neurology, has received the NIH Director’s New Innovator Award, which supports early-career investigators conducting unconventional and innovative research projects in the biomedical, behavioral or social sciences.
Eminent Physician-Scientist Sachin Patel Named Chair of Psychiatry
Sachin Patel, MD, PhD, has been named chair and Lizzie Gilman Professor of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine, and psychiatrist-in-chief at Northwestern Memorial Hospital’s Norman and Ida Stone Institute of Psychiatry.
Krainc to receive $9 Million, 8-year NIH Grant
Dimitri Krainc, MD, PhD, has received a Research Program Award grant from the National Institute of Neurological Disorders and Stroke (NINDS).
Interaction of Mitochondria and Lysosomes Key in Parkinson’s Disease
Prolonged contact between the mitochondria and the lysosome causes aberrant distribution of mitochondria, contributing to neuronal dysfunction in Parkinson’s disease.
Northwestern Faculty Inducted into Prominent Medical Societies
Several Feinberg faculty members have been elected to the American Society for Clinical Investigation (ASCI) and the Association of American Physicians (AAP).
New Genetic Cause of Dystonia Revealed
Northwestern Medicine scientists discovered mutations in a scaffolding protein contributes to dystonia, an incurable movement disorder.
Astrocytes Play Unexpected Role in Parkinson’s Disease
Astrocytes may play a protective role in Parkinson’s disease, slowing alpha-synuclein accumulation in neurons, according to a study published in The Journal of Neuroscience.
Inter-Organelle Contact Drives Calcium Transfer
Inter-organelle contacts drive calcium transfer from lysosomes to mitochondria, findings that lay out a possible therapeutic blueprint for neurological disorders.