November 1, 2016

Dáša Doležalová Bohačiaková Team

Research Interests | Publications | Funding | Team Members | Collaboration | News | Open Positions

PI

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M.Sc. Dasa Bohaciakova (Dolezalova), PhD

email: bohaciakova@med.muni.cz
phone: +420 54949 6052

Address:
Kamenice 3/building A1
Department of Histology and Embryology
Faculty of Medicine, Masaryk University Brno
Czech Republic

ORC ID 0000-0002-9538-6668
Masaryk University,
ResearchGate,
Google Scholar

 

Research interests

  • CURRENT OBJECTIVE:

Our group studies the role of miRNA in differentiation of hESC into neural stem cells (NSCs). We hypothesize that differentiation-associated miRNA contribute to cell cycle regulation in NSCs and help to maintain their unlimited proliferative potential. Our preliminary results show upregulation of numerous miRNAs upon differentiation of hESCs into NSCs. Interestingly, deregulation of several of these has been associated with cancer. Thus studying their expression during normal development in vitro can help to unravel potential candidates for anti-cancer therapy.

  • AREAS OF INTEREST:

Human Embryonic Stem Cells, Differentiation, Neural Stem/Progenitor Cells, Cerebral organoids, microRNA, Cell Cycle, DNA damage, Alzheimer’s disease

 


Publications

Complete list of publications: click here

2017

  • Bohaciakova D*, Renzova T, Fedorova V, Barak M, Kunova Bosakova M, Hampl A, Cajanek L*. An efficient method for generation of Knock-out human embryonic stem cells using CRISPR/Cas9 system. Stem Cells Dev. 2017 Nov 1. https://doi.org/10.1089/scd.2017.0058; *Corresponding authors
  • Bagherpoor AJ, Dolezalova D*, Barta T, Kucirek M, Sani SA, Esner M, Bosakova MK, Vinarsky V, Peskova L, Hampl A, Stros M*. Properties of Human Embryonic Stem Cells and their Differentiated Derivatives Depend on Non-histone DNA-Binding HMGB1 and HMGB2 Proteins. Stem Cells Dev. 2017 Mar 1. PubMed PMID: 27863459; *Corresponding authors
  • Varun D, Srinivasan GR, Tsai YH, Kim HJ, Cutts J, Petty F, Merkley R, Stephanopoulos N, Dolezalova D, Marsala M, Brafman DA. A robust vitronectin-derived peptide for the scalable long-term expansion and neuronal differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs). Acta Biomaterialia. 2017 Jan 15. http://dx.doi.org/10.1016/j.actbio.2016.10.037

2015

  • Juhasova J, Juhas S, Hruska-Plochan M, Dolezalova D, Holubova M, Strnadel J, Marsala S, Motlik J, Marsala M. Time course of spinal doublecortin expression in developing rat and porcine spinal cord: implication in in vivo neural precursor grafting studies. Cellular and molecular neurobiology. 2015 Jan 1. doi:10.1007/s10571-014-0145-7

2014

  • Dolezalova D, Hruska-Plochan M, Bjarkam CR, Sørensen JC, Cunningham M, Weingarten D, Ciacci JD, Juhas S, Juhasova J, Motlik J, Hefferan MP, Hazel T, Johe K, Carromeu C, Muotri A, Bui J, Strnadel J, Marsala M. Pig models of neurodegenerative disorders: Utilization in cell replacement-based preclinical safety and efficacy studies. J Comp Neurol. 2014 Aug 15;522(12):2784-801. doi: 10.1002/cne.23575. Review. PubMed PMID: 24610493.

2013

  • Barta T, Dolezalova D, Holubcova Z, Hampl A. Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture. Exp Biol Med (Maywood). 2013 Mar;238(3):271-5. doi: 10.1177/1535370213480711. Review. PubMed PMID: 23598972.

2012

  • Dolezalova D, Mraz M, Barta T, Plevova K, Vinarsky V, Holubcova Z, Jaros J, Dvorak P, Pospisilova S, Hampl A. MicroRNAs regulate p21(Waf1/Cip1) protein expression and the DNA damage response in human embryonic stem cells. Stem Cells. 2012 Jul;30(7):1362-72. doi: 10.1002/stem.1108. PubMed PMID: 22511267.
  • Mraz M, Dolezalova D, Plevova K, Stano Kozubik K, Mayerova V, Cerna K, Musilova K, Tichy B, Pavlova S, Borsky M, Verner J, Doubek M, Brychtova Y, Trbusek M, Hampl A, Mayer J, Pospisilova S. MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia. Blood. 2012 Mar 1;119(9):2110-3. doi: 10.1182/blood-2011-11-394874. PubMed PMID: 22234685.

2011

  • Holubcová Z, Matula P, Sedláčková M, Vinarský V, Doležalová D, Bárta T, Dvořák P, Hampl A. Human embryonic stem cells suffer from centrosomal amplification. Stem Cells. 2011 Jan;29(1):46-56. doi: 10.1002/stem.549. PubMed PMID: 20960514.

2010

  • Bárta T, Vinarský V, Holubcová Z, Dolezalová D, Verner J, Pospísilová S, Dvorák P, Hampl A. Human embryonic stem cells are capable of executing G1/S checkpoint activation. Stem Cells. 2010 Jul;28(7):1143-52. doi: 10.1002/stem.451. PubMed PMID: 20518019.
  • Borghese L, Dolezalova D, Opitz T, Haupt S, Leinhaas A, Steinfarz B, Koch P, Edenhofer F, Hampl A, Brüstle O. Inhibition of notch signaling in human embryonic stem cell-derived neural stem cells delays G1/S phase transition and accelerates neuronal differentiation in vitro and in vivo. Stem Cells. 2010 May;28(5):955-64. doi: 10.1002/stem.408. PubMed PMID: 20235098.

 


Funding

03/2018 – 2020

  • Title: Transformative stem cell-based model of Alzheimer’s disease and advanced analytics to study the role of membrane lipids in the pathogenesis

Principal Investigator: Zdenek Spacil, PhD
Co-PI: Dasa Bohaciakova, PhD
Institutions: Research Centre for Toxic Compounds in the Environment (RECETOX) / Masaryk University, Brno, Czech Republic

Funding agency: Grant Agency of Masaryk University (GAMU)
Grant Number: MUNI/G/1131/2017
Status: OPEN

2018 – 2020

  • Title:  Functional studies of miRNAs and protein-coding genes involved in stem cell specification during neural development. 

Principal Investigator: Dasa Bohaciakova, PhD
Institution: Masaryk University, Brno, Czech Republic

Funding agency: Grant Agency of the Czech Republic (GACR)
Grant Number: 18-25429Y
Status: OPEN

 

2018/01 – 2019/06

  • Title: Klinicky-využitelné neurální kmenové buňky a studium řízení jejich buněčného dělení.

Principal Investigator: Dasa Bohaciakova, PhD
Institution: Masaryk University, Brno, Czech Republic

Funding agency: Fond Neuron na podporu vedy – Neuron Impuls
Status: OPEN

 

2017

  • Title: In vitro modelování patologie Alzheimerovy choroby pomocí cerebrálních organoidů

Institutional support by Faculty of Medicne MU for junior researchers (2017, PI)

Status: Closed

 

2015 – 2017

  • Title: The role of microRNA in cell cycle regulation and differentiation of human embryonic stem cell-derived neural stem cells.

Principal Investigator: Dasa Dolezalova, PhD
Institution: Masaryk University, Brno, Czech Republic

Funding agency: Grant Agency of the Czech Republic (GACR)
Grant Number: GJ15-18316Y
Status: Closed

 

2016

  • Title: The role of microRNAs in the biology of human embryonic stem cells

Institutional support by Faculty of Medicne MU for junior researchers (2016, PI)

Status: Closed

 

2009 – 2010

  • Title: The role of microRNAs and protein coding genes in human embryonic stem cell response to DNA damage.

Principal Investigator: M.Sc. Dasa Dolezalova
Institution: Masaryk University, Brno, Czech Republic

Funding agency: Grant Agency of Masaryk University (GAMU)
Grant Number: MUNI/G/0132/2009
Status: Closed

 

2007 – 2009

  • Title: Analysis of Effects of Inhibition of Cyclin Dependent Kinases on Differentiation of Human Embryonic Stem Cells.

Principal Investigator: Bc. Dasa Dolezalova
Institution: Masaryk University, Brno, Czech Republic

Funding agency: Grant Agency of Masaryk University (GAMU)
Grant Number: MUNI/31/A0001/2007
Status: Closed

 


Team members

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Bc. Veronika Fedorova – Master thesis student

Project topic: Cell Cycle Regulation in Human Embryonic Stem Cells and Their Differentiated Derivatives

Team member since: September 2015

 

 

 

 

 

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Martin Barak – Medical student working on independent research project as part of the P-Pool study program

Project topic: In vitro Neural Differentiation and Cerebral Organoids

Team member since: July 2016

 

 

 

 

 

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Lina El Rifaie – Medical student working on independent research project

Project topic: Role of p53 in Neural Differentiation and Cerebral Organoid Development

Team member since: July 2017

 

 

 

 

 

 

Alumni:

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M.Sc. Miroslava Peterkova – Diploma thesis Student

Project topic: MicroRNA in Neural Stem Cell Biology

Team member: October 2015 – May 2016

 


Collaboration

 

Neural Differentiation:

  • University of California San Diego, CA, USA – Martin Marsala, MD Department of Anesthesiology
  • Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic (IAPG AS CR) in Libechov, Czech Republic

RNA work:

Alzheimer’s disease:

  • Loschmidt Laboratories – Jiri Damborsky group
  • RECETOX – Zdenek Spacil group
  • ICRC – Katerina Sheardova, Head od the Memory Center by ICRC/FNUSA Brno

 


News

2018

2016

  • 2016/12 – We became part of newly forming Alzheimer’s disease consortium. We will be establishing 3D cerebral organoids for the in vitro AD modeling.

 


Open Positions

Updated: January 2018

Deadline for Registration: April 30 2018

We are currently looking for PhD Students!

Two positions are available on the following projects:

  • Topic 1: Molecular mechanisms of neuronal development in vitro

Title: Role of miRNAs and protein-coding genes involved in stem cell-specification during neural development in vitro.

During the past decade, small non-coding RNAs (miRNAs) were identified as crucial post-transcriptional regulators of gene expression. They were also directly linked with human embryonic stem cell (hESC) physiology and maintenance of key stem cell properties: self-renewal and pluripotency. Importantly, their expression is directly regulated by main stem cell transcription factors – Oct4, Nanog, and Sox2. These pathways are therefore being extensively studied in undifferentiated hESCs. However which molecular mechanisms are employed during the onset of differentiation of hESCs is less well described. Therefore, we aim to study how miRNAs and protein-coding genes function together to maintain neural stem cell-specific properties – i.e. the ability to self-renew and to differentiate. Since deregulation of these processes is a hallmark of cancer and/or neural degeneration, we believe that studying cell-specific transcription factors and/or miRNAs in these two processes will contribute to the gain of knowledge with potential relevance to patients’ treatment in the future.

  • Topic 2: Modeling of Alzheimer’s disease using cerebral organoids and other 2D and 3D in vitro model systems

Title: Using human pluripotent stem cell-based model to study the Alzheimer’s disease pathogenesis in vitro.

Alzheimer’s disease is the most common cause of dementia in elderly population worldwide. The current body of research supports the concept that protein aggregation initiates the onset of Alzheimer’s disease. However, in spite of the large number of available literature and studies, a mechanism of pathogenesis and potential treatment for Alzheimer’s disease remains elusive. Our laboratory has recently implemented a method for derivation of cerebral organoids from human embryonic stem cells. Using this model, as well as other relevant differentiation strategies, we aim to test hypothetical mechanisms of Alzheimer’s disease pathogenesis using patient’s derived pluripotent stem cells. In collaboration with other partners from Masaryk University, we will test several hypotheses of the onset of Alzheimer’s disease. We believe that proposed strategy will bring a new perspective the field of Alzheimer’s disease research.

 

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