Experiments at the laboratory are aimed at understanding the role of microRNAs and hormones in the generation of new neurons in the hippocampus. In doing so, we focus our work in utilizing RNA interference (RNAi) as a tool to study and treating neurologic diseases, such as epilepsy, depression and others, that may be related to chronic alterations in hippocampal neurogenesis

In the laboratory, we use a wide range of RNAi effectors from synthetic siRNAs to short hairpin RNAs and artificial microRNAs. In combination with viruses engineered and optimized to deliver RNAi effectors to stem cells and newborn neurons in the hippocampus in vivo, our experimental approach provides and excellent opportunity to contribute substantially to a currently booming scientific field.

Within this line of research, we are particularly interested in studying the interplay between microRNAs and hormone receptors in the regulation of neural stem cells in vitro and in vivo.

Neural stem cells in vitro give rise
to neurons (red) and glial cells (green)
DNA in the nucleus of all cells is shown in blue

A central interest of the lab is the role of hormone receptors and microRNAs in the regulation of synaptic connectivity at the level of dendritic spines. With this aim we use state-of-the-art confocal microscopy techniques.

A second part of the group’s research focuses on understanding the molecular mechanisms involved in crosstalk between GPCRs and between GPCRs and nuclear receptors for hormones

Past and ongoing collaborations :

• Ron de Kloet, Erno Vreugdenhil and Onno Meijer. Medical Pharmacology Department, LACDR, Leiden.
• Paul Lucassen, Harm Krugers, SILS Center for Neurosciences, University of Amsterdam
• Marian Joels, Rudolf Magnus lab Utrecht and SILS, University of Amsterdam
• Davide de Petri-Tonelli, Department of Neuroscience and Brain Technologies,
  Italian Institute of Technology, Genoa, Italy.
• Federico Monczor, Laboratory of Receptor Pharmacology, Department of Medicinal Chemistry, Faculty of Biochemistry and Pharmacy, University of Buenos Aires, Argentina.
• Dennis Steindler, Department of Neuroscience, The McKnight Brain Institute,
  University of Florida College of Medicine.
• Connie Jimenez, OncoProteomics Laboratory, Dept. Medical Oncology, VUMC-Cancer Center Amsterdam
• Fons Verbeek, Section Imaging & BioInformatics, Leiden Institute of Advanced Computer Science

Carlos P. Fitzsimons, Ph.D, Group Leader

Dr. Fitzsimons studied Biochemistry and Pharmacy and received his M.S. and Ph.D from the University of Buenos Aires, Argentina. He moved to Holland to begin a postdoctoral position at the Leiden/Amsterdam Center for Drug Research, Vrije Universiteit Amsterdam, where he studied the role of G protein coupled receptors (GPCRs) in herpes virus infection.
During a postdoctoral fellowship at the Leiden/Amsterdam Center for Drug Research, University of Leiden, he studied the effects of stress hormones on stems cells of the brain, their maturation and incorporation into the hippocampus circuitry.
Dr Fitzsimons joined the Center for Neurosciences, SILS, UvA as Assistant professor in 2010, within Dr. Lucassen’s group. Dr Fitzsimons laboratory is financed by a VIDI subsidy from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO). His laboratory studies the regulation of neural stem cells by hormones and microRNAs, associated with acute and chronic stress and epilepsy in animal models.

People in the group  

• Carlos Fitzsimons, Assistant Professor
• Robert Eendebak, PhD student
• Gideon Meerhoff, technician

Selected publications

• Expression of a G protein-coupled receptor (GPCR) leads to attenuation of signaling by other GPCRs: experimental evidence for a spontaneous GPCR constitutive inactive form. Tubio MR, Fernandez N, Fitzsimons CP, Copsel S, Santiago S, Shayo C, Davio C, Monczor F.
  J Biol Chem. 2010 May 14;285(20):14990-8. abstract

• Lentivirus-mediated transgene delivery to the hippocampus reveals sub-field specific differences in expression
  van Hooijdonk LW, Ichwan M, Dijkmans TF, Schouten TG, de Backer MW, Adan RA, Verbeek FJ, Vreugdenhil E, Fitzsimons CP
  BMC Neurosci. 2009 Jan 13;10:2      abstract

• MicroRNA 18 and 124a down-regulate the glucocorticoid receptor :
  implications for glucocorticoid responsiveness in the brain.
  Vreugdenhil E, Verissimo CS, Mariman R, Kamphorst JT, Barbosa JS, Zweers T, Champagne DL, Schouten T, Meijer OC, de Kloet ER, Fitzsimons CP. Endocrinology. 2009 May;150(5):2220-8.      abstract

• The microtubule-associated protein doublecortin-like regulates the transport
  of the glucocorticoid receptor in neuronal progenitor cells
  Fitzsimons CP, Ahmed S, Wittevrongel CF, Schouten TG, Dijkmans TF,
  Scheenen WJ, Schaaf MJ, de Kloet ER, Vreugdenhil E.
  Mol Endocrinol. 2008 Feb;22(2):248-62      abstract

• Mepyramine, a histamine H1 receptor inverse agonist, binds preferentially to a G protein-coupled form of the receptor and sequesters G protein
  Fitzsimons CP, Monczor F, Fernández N, Shayo C, Davio C.
  J Biol Chem. 2004 Aug 13;279(33):34431-9      abstract