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AG Kye
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AG Kye

Group leader

Dr. rer. nat. Min Jeong Kye

Institute of Human Genetics
University Hospital of Cologne
Building 47, 9th floor
Kerpener Str. 34
50931 Cologne

Germany

 

Group members

 

Research focus

  • RNA biology in neurological disorders
  • Spatial regulation of gene expression
  • Cell to cell interaction in nervous system

 

Protein homeostasis is important for cellular survival and function, and protein synthesis and degradation are tightly regulated. In polarized cells like neurons, subcellular compartments contain different sets of proteins and their expressions are spatially segregated and transient. To explain this phenomenon, it has been suggested that proteins can be locally translated and degraded at subcellular compartments such as dendrites and axonal terminals. This can explain neuron specific phenomena such as axonal pathfinding and synaptic plasticity, which require spatial and temporal regulation of protein expression. Several mechanisms regulating specific protein translation have been suggested in neurons, including microRNA (miRNA) mediated translational repression and mTOR mediated translational activation. Importantly, multiple lines of evidence over the past decade have indicated critical roles for local protein homeostasis in association with neurological disorders as diverse as spinal muscular atrophy (SMA), autism spectrum disorders, and Alzheimer’s disease. However, the mechanistic underpinning of dysregulated protein homeostasis in neurological disorders remains elusive.

Major research interests in Kye’s group are understanding of:

1) The role of miRNA and RNA binding proteins in neurological disorders

2) Spatial regulation of gene expression in nervous system during development and synaptic plasticity with focus on miRNA and RNA binding protein mediated protein synthesis

3) Inter- and intra cellular mechanisms underlying neuronal connectivity between neurons, also neurons with none-neuronal cells.

 

Publications of the last five years

2017

O'Hern PJ, do Carmo G Gonçalves I, Brecht J, López Soto EJ, Simon J, Chapkis N, Lipscombe D, Kye MJ, Hart AC.
Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models.
Elife. 2017.

PubMed PMID: 28463115

Riessland M, Kaczmarek A, Schneider S, Swoboda KJ, Löhr H, Bradler C, Grysko V, Dimitriadi M, Hosseinibarkooie S, Torres-Benito L, Peters M, Upadhyay A, Biglari N, Kröber S, Hölker I, Garbes L, Gilissen C, Hoischen A, Nürnberg G, Nürnberg P, Walter M, Rigo F, Bennett CF, Kye MJ, Hart AC, Hammerschmidt M, Kloppenburg P, Wirth B.
Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis.
Am J Hum Genet. 2017;100(2):297-315.

PubMed PMID: 28132687

2016

G Golçalves ID, Rehorst WA, Kye MJ.
DYS-regulation of RNA mediated gene expression in motor neuron diseases.
CNS Neurol Disord Drug Targets. 2016;15:887-95.

PubMed PMID: 27577737

Hosseinibarkooie S, Peters M, Torres-Benito L, Rastetter RH, Hupperich K, Hoffmann A, Mendoza-Ferreira N, Kaczmarek A, Janzen E, Milbradt J, Lamkemeyer T, Rigo F, Bennett CF, Guschlbauer C, Büschges A, Hammerschmidt M, Riessland M, Kye MJ, Clemen CS, Wirth B.
The Power of Human Protective Modifiers: PLS3 and CORO1C Unravel Impaired Endocytosis in Spinal Muscular Atrophy and Rescue SMA Phenotype.
Am J Hum Genet. 2016 Sep 1;99(3):647-65.
PubMed PMID: 27499521

Highlight and FREE featured article AJHG

Heesen L, Peitz M, Torres-Benito L, Hölker I, Hupperich K, Dobrindt K, Jungverdorben J, Ritzenhofen S, Weykopf B, Eckert D, Hosseini-Barkooie SM, Storbeck M, Fusaki N, Lonigro R, Heller R, Kye MJ, Brüstle O, Wirth B.
Plastin 3 is upregulated in iPSC-derived motoneurons from asymptomatic SMN1-deleted individuals.
Cell Mol Life Sci. 2015

PubMed PMID: 26573968

2014

Kye MJ, Niederst ED, Wertz MH, Gonçalves ID, Akten B, Dover KZ, Peters M, Riessland M, Neveu P, Wirth B, Kosik KS, Sardi SP, Monani UR, Passini MA, Sahin M.
SMN regulates axonal local translation via miR-183/mTOR pathway.
Hum Mol Genet. 2014 Dec 1;23(23):6318-31

PubMed PMID: 25055867

Kye MJ and Gonçalves ID; The role of miRNA in motor neuron disease.
Front Cell Neurosci. 2014 Jan 30;8:15. eCollection 2014. Review.

PubMed PMID: 24523674

2013

Dimitriadi M, Kye MJ, Kalloo G, Yersak JM, Sahin M and Hart AC; The neuroprotective drug riluzole acts via small conductance Ca2+-activated K+ channels to ameliorate defects in Spinal Muscular Atrophy models.
J Neurosci. 2013 April 10; 33(15): 6557– 62

PubMed PMID: 2357853

2012

Weeraratne SD, Amani V, Teider N, Pierre-Francois J, Winter D, Kye MJ, Sengupta S, Archer T, Remke M, Bai AH, Warren P, Pfister SM, Steen JA, Pomeroy SL, Cho YJ; Pleotropic effects of miR-183~96~182 converge to regulate cell survival, proliferation and migration in medulloblastoma.
Acta Neuropathol. 2012 Apr; 123(4): 539-52

PubMed PMID: 22402744

2011

Akten B, Kye M, Hao LT, Wertz MH, Singh S, Nie D, Huang J, Merianda TT, Twiss JL, Beattie CE, Steen JAJ and Sahin M; Interaction of survival motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits.
Proc Natl Acad Sci USA. 2011 Jun 21; 108(25): 10337-42

PubMed PMID: 21652774

Kye M, Neveu P, Lee YS, Zhou M, Steen JJ, Sahin M, Kosik KS and Silva AJ; NMDA mediated contextual conditioning changes miRNA expression.
PLoS One, 2011; 6(9): e24682

PubMed PMID: 21931811