Jump to top menu Jump to main menu Jump to content
Research group/lab  |  PI. Vincenzo Bonifati, MD, PhD

Molecular Mechanisms of Movement Disorders

We focus on finding genes involved in Parkinson’s disease and related neurodegenerative disorders (PD-dementia, Dementia with Lewy bodies) and other movement disorders.

About our research group/lab

Our research

Molecular mechanisms of movement disorders

We are searching for genes involved in Parkinson’s disease (PD) and other movement disorders. The search may provide clues for understanding of the disease mechanisms and identifying novel targets for therapies to stop and prevent these diseases. PD is a common degenerative disease of the brain with progressive loss of dopaminergic neurons and the formation of neuronal inclusions (Lewy bodies) in the surviving neurons. Much of the pathogenesis of PD is unknown. Yet, a growing list of gene defects identified in some inherited forms offers unprecedented, exciting opportunities to disentangle the complex molecular pathways leading to PD.

Gene finding

My group uses a number of unbiased strategies to identify novel genes causing or predisposing to PD and other movement disorders, such as dystonias, paroxysmal dyskinesias, and restless legs syndrome. Our experimental approaches include family-based linkage mapping, homozygosity mapping, positional cloning, next-generation sequencing technologies (exome sequencing and whole genome sequencing), and tools for in-silico analysis of DNA and protein sequence data.

gene finding

Functional studies

Each of the Mendelian forms of disease might provide important clues for understanding of the pathogenesis; also in the more common, complex forms of the disease.

molecular mechanism
 
In 2018, we reported in the Lancet Neurology the identification of LRP10 gene variants associated with familial PD and Dementia with Lewy bodies. To investigate the function of LRP10 in synucleinopathies, we use iPS-derived neuronal and glial cell cultures and brain organoids from LRP10 patients and controls, unbiased brain and single-cell transcriptomic and proteomic strategies.

Key Publications

LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study.Quadri M, Mandemakers W, Grochowska MM, Masius R, Geut H, Fabrizio E, Breedveld GJ, Kuipers D, Minneboo M, Vergouw LJM, Carreras Mascaro A, Yonova-Doing E, Simons E, Zhao T, Di Fonzo AB, Chang HC, Parchi P, Melis M, Correia Guedes L, Criscuolo C, Thomas A, Brouwer RWW, Heijsman D, Ingrassia AMT, Calandra Buonaura G, Rood JP, Capellari S, Rozemuller AJ, Sarchioto M, Fen Chien H, Vanacore N, Olgiati S, Wu-Chou YH, Yeh TH, Boon AJW, Hoogers SE, Ghazvini M, IJpma AS, van IJcken WFJ, Onofrj M, Barone P, Nicholl DJ, Puschmann A, De Mari M, Kievit AJ, Barbosa E, De Michele G, Majoor-Krakauer D, van Swieten JC, de Jong FJ, Ferreira JJ, Cossu G, Lu CS, Meco G, Cortelli P, van de Berg WDJ, Bonifati V; International Parkinsonism Genetics Network. (2018). Lancet Neurol. 2018 Jul;17(7):597-608.


PTRHD1 Loss-of-function mutation in an african family with juvenile-onset Parkinsonism and intellectual disability.
Kuipers DJS, Carr J, Bardien S, Thomas P, Sebate B, Breedveld GJ, van Minkelen R, Brouwer RWW, van Ijcken WFJ, van Slegtenhorst MA, Bonifati V, Quadri M. (2018). Mov Disord. 2018 Nov;33(11):1814-1819.

ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia.Christian G. Bouwkamp, Zaid Afawi, Aviva Fattal-Valevski, Inge E. Krabbendam, Stefano Rivetti, Rafik Masalha, Marialuisa Quadri, Guido J. Breedveld, Hanna Mandel, Muhammad Abu Tailakh, H. Berna Beverloo, Giovanni Stevanin, Alexis Brice, Wilfred F.J. van IJcken, Meike W. Vernooij, Amalia M. Dolga, Femke M.S. de Vrij, Vincenzo Bonifati, Steven A. Kushner. (2018). First published March 21, 2018, DOI: https://doi.org/10.1212/NXG.0000000000000223.

Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia.De Vrij FM, Bouwkamp CG, Gunhanlar N, Shpak G, Lendemeijer B, Baghdadi M, Gopalakrishna S, Ghazvini M, Li TM, Quadri M, Olgiati S, Breedveld GJ, Coesmans M, Mientjes E, de Wit T, Verheijen FW, Beverloo HB, Cohen D, Kok RM, Bakker PR, Nijburg A, Spijker AT, Haffmans PMJ, Hoencamp E, Bergink V; GROUP Study Consortium, Vorstman JA, Wu T, Olde Loohuis LM, Amin N, Langen CD, Hofman A, Hoogendijk WJ, van Duijn CM1, Ikram MA, Vernooij MW, Tiemeier H, Uitterlinden AG, Elgersma Y, Distel B, Gribnau J, White T, Bonifati V, Kushner SA. (2019). Mol Psychiatry. 2019 May;24(5):757-771.

An update on the genetics of dementia with Lewy bodies.
Vergouw LJM, van Steenoven I, van de Berg WDJ, Teunissen CE, van Swieten JC, Bonifati V, Lemstra AW, de Jong FJ. (2017). Parkinsonism Relat Disord. 2017 Oct;43:1-8.

Collaborations

Collaboration outside of Erasmus MC

Our laboratory research relies on the dedication and the excellent investigations performed by a network of collaborators (mostly neurologists) operating in the Netherlands, Italy, Portugal, Spain, Brazil, Taiwan, and other countries, to study large families with Mendelian neurodegenerative disease, other movement disorders, as well as case-control series, and genetically isolated populations. We are also conducting a research program on the genetics of PD in Sardinia, a Mediterranean genetic isolate.

Funding & Grants

  • 2016 EU Joint Programme - Neurodegenerative Disease Research (JPND) (site-PI, Consortium grant)
    Advanced modeling of Parkinson's disease with three-dimensional human midbrain organoids.
  • 2016 Stichting Parkinson Fonds Grant (PI)
    Exome sequencing in Parkinson’s disease.
  • 2018 Stichting Parkinson Fonds Grant (PI)
    Role of LRP10 in the pathogenesis of Parkinson’s disease.

Our team

Principal Investigator

  • Vincenzo Bonifati, MD, PhD, Group Head
    contact

Research team members

  • Wim Mandemakers, PhD, Staff scientist
  • Guido Breedveld, BSc, Senior Research Technician
  • Ana Carreras Mascaró, PhD Student
  • Martyna Grochowska, PhD Student
  • Christina Fevga, PhD student
  • Demy Kuipers, BSc, Research Technician
  • Federico Ferraro, MSc, Visiting Research Fellow
  • Rocco Calandro, MSc student
  • Domenico Natale, MSc student

Any questions or comments?

Please contact our office.

Contact form