Laboratory of Preclinical Testing of Higher Standard

Head: Urszula Wojda

Staff: Anna Mietelska-Porowska, Mikołaj Zdioruk, Anna Piotrowska, Katarzyna Laskowska-Kaszub (PhD student), Joanna Wojsiat (PhD student), Chiara Prandelli (PhD student)

Research profile:
Currently organized competence centre/core-facility with its own research program.

The laboratory mission as a competence centre is translation of discoveries from basic neuroscience to clinical trials. The lab offers expertise in designing, performing and analyzing preclinical tests involving pharmacodynamic, pharmacokinetic, and toxicology assays of potential novel biologically active compounds and therapeutic strategies against human diseases, mainly neurodegenerative disorders. Studies are performed according to higher standard and Good Laboratory Practice rules, using cellular and animal disease models. The offer is directed to other research groups and biotech companies in Poland and abroad (collaboration or contracts).

The laboratory own research program concentrates on molecular mechanisms of Alzheimer’s disease (AD) with a special emphasis on the role of aberrant cell cycle regulation and calcium signaling impairment. These processes are being studied at the genomic, proteomic, and cellular levels. We also investigate systemic changes in AD, mainly in blood lymphocytes. These studies aim at identification of early disease markers and design of new therapeutic strategies in AD. Moreover, as lack of human neuronal models has so far limited preclinical drug testing, we develop and evaluate novel models employing human induced Pluripotent Stem Cells (iPSC).

Methods:
• assays of drug safety in mice/rat
• cellular cultures incl. primary neurons and iPSC
• molecular biology methods (qPCR, transfections, RNAi)
• microscopy (immunocytochemistry, immunofluorescence)
• biochemical assays (protein-protein interactions)

Current research activities:
• analyses of patient-specific neurons derived from iPSC as new tools for studying molecular mechanisms of AD and for drug testing
• the role of aberrant cell cycle regulation and apoptosis in neuronal progenitors, mature neurons and lymphocytes in AD pathogenesis; involvement of p53-p21 signaling
• the functions of calcium signaling calmyrin (CaMy) proteins in neuronal physiology and neurodegeneration
• commonalities and differences of molecular mechanisms in sporadic and familial AD

UE Horizon 2020 FETOPEN grant at the Nencki Institute

 

Prof. Urszula Wojda is a member of an international consortium that has received a EU Horizon 2020 grant in the FETOPEN: Research & Innovation Action, Novel Ideas for Radically New Technologies competition. The aim of the consortium’s research is to develop new strategies for the treatment and diagnosis of Alzheimer's disease based on studies of glycobiological alterations in AD. The “ArrestAD” project received the highest possible evaluation of reviewers (15/15).

The consortium of the "ArrestAD" project includes the following entities:

Consortium leader: University of Paris Est Créteil FR

  • THE UNIVERSITY OF LIVERPOOL UK
  • STICHTING KATHOLIEKE UNIVERSITEIT NL
  • INSTYTUT BIOLOGII DOSWIADCZALNEJ IM. M. NENCKIEGO POLSKIEJ AKADEMII NAUK PL
  • FUNDACION DE INVESTIGACION DEL CANCER DE LA UNIVERSIDAD DE SALAMANCA ES
  • ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS FR
  • UNIVERSITAT AUTONOMA DE BARCELONA ES 
  • SCREENCELL Company


Prof. Urszula Wojda with her group from the Laboratory of Preclinical Studies of Higher Standard of the Neurobiology Centre at the Nencki Institute examines the relationships between genetic and proteomic factors of AD and changes of glycosaminoglycans in blood cells, as a basis for developing new strategies for the early diagnosis of AD. Blood samples for the research are provided by Prof. Thomas Gabryelewicz’s team from the Alzheimer’s Ward of the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw.

 

http://cordis.europa.eu/project/rcn/207479_en.html

 

 

Selected publications:

Wojda U., Kuźnicki J. (2013) Alzheimer’s disease modeling: ups, downs, and perspectives for human induced pluripotent stem cells. Journal of Alzheimer’s Disease, 34(3): 563-588.

Esteras N., Alquézar C., Bermejo-Pareja F., Białopiotrowicz E., Wojda U, .Martín-Requero A. (2013) Downregulation of extra- cellular signal-regulated kinase 1/2 activity by calmodulin KII modulates p21Cip1 levels and survival of immortalized lymphocytes from Alzheimer’s disease patients. Neurobiology of Aging, 34(4): 1090-1100.

Białopiotrowicz E., Szybińska A., Kuźniewska B., Buizza L., Uberti D., Kuźnicki J., Wojda U. (2012) Highly pathogenic Alzheim- er’s disease presenilin 1 P117R mutation causes a specific increase in p53 and p21 protein levels and cell cycle dysregulation in human lymphocytes. Journal of Alzheimer’s Disease, 32: 397-415.

Białopiotrowicz E., Kuźniewska B., Kachamakova-Trojanowska N., Barcikowska M.,Kuźnicki J., Wojda U. (2011) Cell cycle regulation distinguishes lymphocytes from sporadic and familial AD patients. Neurobiology of Aging, 32: 2319.e13-26.

Sobczak A., Dębowska K., Błażejczyk M., Kreutz M.R., Kuźnicki J., Wojda U. (2011) Calmyrin1 binds to SCG10 protein (stathmin2) to modulate neurite outgrowth. Biochimica et Biophysica Acta, 1813: 1025-