Department of Medical Biotechnology

Dr. hab. Agnieszka Fiszer, prof. IBCH PAS

Head of Department:

agnieszka.fiszer@ibch.poznan.pl
ext. 1450

Research activity

Research area

Research at the Department of Medical Biotechnology concerns the diversity of RNA functions and dysfunctions in the context of repeated tracts and neurodegenerative diseases.

Our research focuses on trinucleotide repeat sequences (mainly CAG) and their expansion related to polyglutamine (polyQ) diseases that include Huntington's disease (HD) and spinocerebellar ataxias (SCAs).

We aim to precisely describe new molecular pathogenic pathways for polyQ diseases, with particular emphasis on RNA-dependent pathways and changes in the level of various types of RNA. We investigate the functioning of mutant mRNA containing CAG repeat expansion, as it is a very promising target for oligonucleotide-based tools in therapeutic approaches. We are also interested in determining the function of repeat tracts in wild-type RNAs, including non-coding RNAs.

MAIN RESEARCH TOPICS

RNA and protein toxicity markers in polyQ diseases
Establishment and characteristics of new cellular and mouse models
Investigation of molecular interactions with trinucleotide repeat tracts in RNAs
Role of non-coding RNAs in the pathogenesis of polyQ diseases
Investigation of RAN translation and alternative polyadenylation events for transcripts with repeat expansions
Design and testing of oligonucleotide-based therapeutic strategies

Keywords

triplet repeat expansion diseases,
polyglutamine diseases pathogenesis,
RNA and protein toxicity,
therapeutic strategies,
RNA interference technology,
microRNAs, non-coding RNAs,
iPSC technology,
cellular models,
mouse models

Research Projects

Ongoing research projects:

Function and dysfunction of repeated tracts in non-coding and protein-coding transcripts (NCN OPUS, PI: A. Fiszer)
MyRIAD: (Micro)RNA and informatics approaches for diagnosis, prognosis and treatment of Alzheimer’s disease and Dementia (International project JPND, Consortium leader: K. Whysall-Goljanek, University of Galway; PI: A. Fiszer)
Development of a universal fast-response platform, based on RNA technology, ensuring the national drug and epidemiological safety (one of the teams involved from IBCH, ABM Project Call: Development of innovative therapeutic solutions with RNA technology, Consortium leader: Polfa S.A., PI: prof. M. Figlerowicz)

Selected publications

Joachimiak P, Ciesiolka A, Kozlowska E, Switonski PM, Figura G, Ciolak A, Adamek G, Surdyka M, Kalinowska-Poska Z, Figiel M, Caron NS, Hayden MR, Fiszer A.
Allele-specific quantitation of ATXN3 and HTT transcripts in polyQ disease models
BMC Biology 2023; 21:17
Fiszer A.
All roads lead to cure: Diversity of oligonucleotides in DM1 therapy
Mol Ther Nucleic Acids. 2023;32:898-899
Nowak B, Kozlowska E, Pawlik W, Fiszer A.
Atrophin-1 function and dysfunction in dentatorubral–pallidoluysian atrophy
Movement Disorders 2023 DOI: 10.1002/mds.29355
Piwecka M, Fiszer A, Rolle K, Olejniczak M.
RNA Regulation in Brain Function and Disease 2022 (NeuroRNA) - Conference Report
Frontiers in Molecular Neuroscience vol.16 2023 doi.org/10.3389/fnmol.2023.1133209
Joachimiak P, Ciesiolka A, Figura G, Fiszer A.
Implications of Poly(A) Tail Processing in Repeat Expansion Diseases.
Cells. 2022;11(4):677
Ciesiolka A, Stroynowska-Czerwinska A, Joachimiak P, Ciolak A, Kozlowska E, Michalak M, Dabrowska M, Olejniczak M, Raczynska KD, Zielinska D, Wozna-Wysocka M, Krzyzosiak WJ, Fiszer A.
Artificial miRNAs targeting CAG repeat expansion in ORFs cause rapid deadenylation and translation inhibition of mutant transcripts.
Cell Mol Life Sci. 2021;78(4):1577-1596.
Koscianska E, Kozlowska E, Fiszer A.
Regulatory Potential of Competing Endogenous RNAs in Myotonic Dystrophies.
Int J Mol Sci. 2021;22(11):6089.
Wozna-Wysocka M, Przybyl L, Jazurek-Ciesiolka M, Switonski PM, Suszynska-Zajczyk J, Sobieszczanska P, Wronka D, Misiorek JO, Figura G, Ciesiolka A, Krzyzosiak WJ, Figiel M, Fiszer A.
Novel HD mouse models enabling new pathogenic mechanisms discovery.
Journal of Neurology, Neurosurgery & Psychiatry, 2021, 92 (Suppl 1) A10 (conference abstract)
Przybyl L, Wozna-Wysocka M, Kozlowska E, Fiszer A.
What, When and How to Measure-Peripheral Biomarkers in Therapy of Huntington's Disease.
Int J Mol Sci. 2021;22(4):1561.
Tymoniuk B, Zmora P, Latowska J, Grabowska A, Ciesiolka A, Joachimiak P, Figura G, Borowiec M, Rolle K, Handschuh L, Fiszer A.
Genetic tests based on the RT-PCR reaction in the diagnostics of SARS-CoV-2 infection.
Przegl Epidemiol. 2021;75(1):14-26.
Jazurek-Ciesiolka M, Ciesiolka A, Komur AA, Urbanek-Trzeciak MO, Krzyzosiak WJ, Fiszer A.
RAN translation of the expanded CAG repeats in the SCA3 disease context.
J Mol Biol. 2020;432(24):166699
Ciolak A, Krzyzosiak WJ, Kozlowska E, Fiszer A.
Generation of human iPS cell line IBCHi002-A from spinocerebellar ataxia type 3/Machado-Joseph disease patient's fibroblasts.
Stem Cell Res. 2020 Apr 20;45:101796. doi: 10.1016/j.scr.2020.101796.
Dabrowska M, Ciolak A, Kozlowska E, Fiszer A, Olejniczak M.
Generation of New Isogenic Models of Huntington's Disease Using CRISPR-Cas9 Technology.
Int J Mol Sci. 2020 Mar 8;21(5). pii: E1854. doi: 10.3390/ijms21051854.
Krzyzosiak WJ, Olejniczak M, Galka-Marciniak P, Fiszer A.
Nucleic acid molecule, expression cassette, expression vector, eukaryotic host cell, induction method of RNA interference in eukaryotic host and use of the nucleic acid molecule in therapy of diseases induced by expansion of trinucleotide CAG repeats
US10329566B2 (international patent)

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