Subarea 4: Cell Dynamics and Molecular Damages in Aging

The research focus of Subarea 4 is on studying damages of macromolecules (proteins, nucleic acids) and determining the structure-function relationship of biomolecules relevant to damage and damage repair processes and responses to molecular damage that might lead to aging and aging-associated pathologies.

The studies are focused on the following research areas: DNA replication, DNA damage responses (DDR), stress responses, metabolic stresses, protein trafficking and protein damages.

The research is defined by four focus areas:

  • DNA damage response in tissue homeostasis and neuropathies,
  • Quality control in the endoplasmic reticulum for secretory pathway in aging processes,
  • Intrinsic and extrinsic factors implicated in cellular decline during aging, and
  • DNA replication and genomic integrity preventing premature aging and diseases.

Research focus of Subarea 4.

The accumulation of damaged macromolecules or subcellular organelles is associated with dysfunction of a cell, which contributes to tissue & organ failure. DNA damage, genomic instability, protein misfolding or defects in toxic protein degradation can compromise cell functionality. Alterations of mitochondrial DNA and protein complexes affect cellular metabolism, which will have a general impact on cell integrity.

Publications

(since 2016)

2020

  • Bi-allelic HPDL Variants Cause a Neurodegenerative Disease Ranging from Neonatal Encephalopathy to Adolescent-Onset Spastic Paraplegia.
    Husain RA, Grimmel M, Wagner M, Hennings JC, Marx C, Feichtinger RG, Saadi A, Rostásy K, Radelfahr F, Bevot A, Döbler-Neumann M, Hartmann H, Colleaux L, Cordts I, Kobeleva X, Darvish H, Bakhtiari S, Kruer MC, Besse A, Ng ACH, Chiang D, Bolduc F, Tafakhori A, Mane S, Ghasemi Firouzabadi S, Huebner AK, Buchert R, Beck-Woedl S, Müller AJ, Laugwitz L, Nägele T, Wang ZQ, Strom TM, Sturm M, Meitinger T, Klockgether T, Riess O, Klopstock T, Brandl U, Hübner CA, Deschauer M, Mayr JA, Bonnen PE, Krägeloh-Mann I, Wortmann SB, Haack TB
    Am J Hum Genet 2020 (epub ahead of print)
  • Cell Metabolic Alterations due to Mcph1 Mutation in Microcephaly.
    Journiac N, Gilabert-Juan J, Cipriani S, Benit P, Liu X, Jacquier S, Faivre V, Delahaye-Duriez A, Csaba Z, Hourcade T, Melinte E, Lebon S, Violle-Poirsier C, Oury JF, Adle-Biassette H, Wang ZQ, Mani S, Rustin P, Gressens P, Nardelli J
    Cell Rep 2020, 31(2), 107506
  • A Caenorhabditis elegans ortholog of human selenium-binding protein 1 is a pro-aging factor protecting against selenite toxicity.
    Köhnlein* K, Urban* N, Guerrero-Gómez D, Steinbrenner H, Urbánek P, Priebs J, Koch P, Kaether C, Miranda-Vizuete A, Klotz LO
    Redox Biol 2020, 28, 101323 * equal contribution
  • Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells.
    Marx-Blümel L, Marx C, Weise F, Frey J, Perner B, Schlingloff G, Lindig N, Hampl J, Sonnemann J, Brauer D, Voigt A, Singh S, Beck B, Jäger UM, Wang ZQ, Beck JF, Schober A
    PLoS One 2020, 15(6), e0234638
  • Growth inhibitory role of the p53 activator SCH 529074 in non‑small cell lung cancer cells expressing mutant p53.
    Nenkov M, Ma Y, Haase D, Zhou Z, Li Y, Petersen I, Lu G, Chen Y
    Oncol Rep 2020, 43(2), 2073-82

2019

  • C/EBPβ-LIP induces cancer-type metabolic reprogramming by regulating the let-7 /LIN28B circuit in mice.
    Ackermann T, Hartleben* G, Müller* C, Mastrobuoni G, Groth M, Sterken BA, Zaini MA, Youssef SA, Zuidhof HR, Krauss SR, Kortman G, de Haan G, de Bruin A, Wang ZQ, Platzer M, Kempa S, Calkhoven CF
    Commun Biol 2019, 2, 208 * equal contribution
  • In vivo Study of Human DHX9 Helicase Functions
    Aly YSH
    Dissertation 2019, Jena, Germany
  • A disease causing ATLASTIN 3 mutation affects multiple endoplasmic reticulum-related pathways.
    Behrendt L, Kurth I, Kaether C
    Cell Mol Life Sci 2019, 76(7), 1433-45
  • BRCA1 mislocalization leads to aberrant DNA damage response in heterozygous ABRAXAS1 mutation carrier cells.
    Bose M, Sachsenweger J, Laurila N, Parplys AC, Willmann J, Jungwirth J, Groth M, Rapakko K, Nieminen P, Friedl TWP, Heiserich L, Meyer F, Tuppurainen H, Peltoketo H, Nevanlinna H, Pylkäs K, Borgmann K, Wiesmüller L, Winqvist** R, Pospiech** H
    Hum Mol Genet 2019, 28(24), 4148-60 ** co-corresponding authors
  • Early-life Pb exposure as a potential risk factor for Alzheimer's disease: are there hazards for the Mexican population?
    Chin-Chan M, Cobos-Puc L, Alvarado-Cruz I, Bayar M, Ermolaeva M
    J Biol Inorg Chem 2019, 24(8), 1285-303