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Carlos Villaescusa

Senior researcher

Visiting address : Karolinska Universitetssjukhuset, Solna, Cmm (L8:00) 171 76 Stockholm, Sweden
Delivery address : Karolinska Universitetssjukhuset, Solna, Cmm (L8:00) 171 76 Stockholm, Sweden

About me

I am a molecular biologist backed by many years of work in the areas of developmental biology, neuroscience and stem cells. After finishing my degree in Barcelona, I moved to Milan, Italy, to the laboratory of Dr. Francesco Blasi to start a PhD in Biochemistry and Molecular Biology and co-supervised by Dr. Riaz Farookhi, at McGill University in Montreal, Canada, in the area of ​​developmental biology. In 2007, I moved to the Karolinska Institutet to work on stem cell research, in the laboratory of Professor Ernest Arenas, who was devoted to stem cell research for cell replacement therapies for the treatment of Parkinson's disease. Over the last years, I have moved into a new and fascinating area of ​​research to model psychiatric disorders such as bipolar disorder, schizophrenia and depression with patient-derived stem cells in the Center for Molecular Medicine (Karolinska University Hospital and Karolinska Institutet). My team, the Psychiatric Stem Cell Group, is part of the Neurogenetics Unit (Professor Martin Schalling). We have also started a scientific platform – OrganoidCellStem – for the generation of human organoids.

Education

Bachelor Degree in Biochemistry by the Universitat Autonoma of Barcelona.

PhD in Biochemistry and Molecular Biology under the supervision of Dr. Francesco Blasi (IFOM Institute, Milan, Italy) and Dr. Riaz Farookhi (McGill University, Montreal, Canada).

FEBS postdoctoral fellow in the group of Dr. Ernest Arenas (MBB Department, Karolinska Institutet).

Research description

Our main focus is to develop cellular models to study psychiatric disorders with patient-derived stem cells and organoids.

 

PSYCHIATRIC STEM CELL GROUP

Our multidisciplinary team together with our collaborators has a solid background in neurobiology, psychiatric disorders, human embryonic stem cells and patient-derived stem cells (iPSC), and cell replacement therapies for neuroregeneration.

It is quite challenging to obtain live neurons from patients affected by psychiatric disorders. Our group is using human cell-based models to generate nearly limitless quantities of live patient-derived mature neurons to identify cellular and molecular changes associated to psychiatric disorders. The patient-derived iPSCs and subsequently in vitro differentiation into neurons provide the opportunity to study enough patient-derived materials to identify neuronal alterations and to develop novel therapeutic approaches.

Bipolar Disorder is characterized by recurrent episodes of depression and mania that causes unusual shifts in mood and results in damaged social relationships and poor job performance. Unfortunately, suicide is a leading cause of death in patient with bipolar disorder. Our group is developing a translational project merging clinical and basic research and disease modeling by patient-derived iPSCs to identify novel biomarkers to predict the success of pharmacological treatments for bipolar disorder. The molecular mechanism related to lithium response is one of our main focuses.

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common childhood disorders. Symptoms include difficulty staying focused and paying attention, difficulty controlling behavior, and hyperactivity. Our group is developing cellular models to identify cellular and molecular phenotypes to understand the origin and progression of ADHD, and to study the brain-gut axis.

 

CMM-OrganoidCellStem

The Center for Molecular Medicine Stem Cell & Organoid Core Facility (CMM-OrganoidCellStem) is located at CMM, Karolinska University Hospital, with the aim to accelerate research in the clinical applications of human stem cells by facilitating the generation and distribution of human pluripotent stem cells (hPSC), derived cells and organoids.

Our facility offers the possibility of differentiate hPSC into different types of derived cells of the mesoderm, ectoderm and endoderm lineages. Our main focus is the production of organoids to advances translational research. Organoid models include three dimensional cell culture systems that closely resemble the in vivo organ or tissue. Organoids reproduce the complex spatial morphology of a tissue including relevant cell-cell and cell-matrix interactions. This is in contrast to traditional two dimensional cell culture models.

 

GROUP MEMBERS:

Karol Kaiser (PhD student)

Vincent Millischer (PhD student)

Parvin Kumar (PhD student)

Paschalis Efstathopoulos (Postdoc)

 

collaborators:

Dr. Martin Schalling, CMM, Karolinska Institute, Stockholm, Sweden.

Dr. Roger Barker, CBR Institute, University of Cambridge, UK. 

Dr. Licia Celery, Cornell University, New York, USA.

Dr. David Hicks, the Department of Neurobiology of Rhythms, için, Strasbourg, France.

Dr. Elizabeth Villela, Psychiatric Hospital Pere Mata, Rovira i Virgili University, Reus, Spain.

Dr. Anna Falk, Neuroscience Department, Karolinska Institute, Stockholm, Sweden.

Dr. Tibor Harkany, Center for Brain Research, Medical University of Vienna, Austria.

 

Links

Publications

A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease
Villaescusa Jc, Li B, Toledo Em, Rivetti Di Val Cervo P, Yang S, Stott Sr, et al
The EMBO journal 2016;35(18):1963-78

Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression
Wei Yb, Liu Jj, Villaescusa Jc, Åberg E, Brené S, Wegener G, et al
Translational psychiatry 2016;6():e869-

MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro
Wei Yb, Melas Pa, Villaescusa Jc, Liu Jj, Xu N, Christiansen Sh, et al
The international journal of neuropsychopharmacology 2016;19(12):-

Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells
La Manno G, Gyllborg D, Codeluppi S, Nishimura K, Salto C, Zeisel A, et al
Cell 2016;167(2):566-580.e19

How to make a midbrain dopaminergic neuron
Arenas E, Denham M, Villaescusa Jc
Development (Cambridge, England) 2015;142(11):1918-36

WNT signaling in midbrain dopaminergic neuron development and cell replacement therapies for Parkinson's disease
Arenas E, Saltó C, Villaescusa C
SpringerPlus 2015;4(Suppl 1):L49-

Cxcl12/Cxcr4 signaling controls the migration and process orientation of A9-A10 dopaminergic neurons
Yang S, Edman Lc, Sánchez-alcañiz Ja, Fritz N, Bonilla S, Hecht J, et al
Development (Cambridge, England) 2013;140(22):4554-64

Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells
Andersson Er, Saltó C, Villaescusa Jc, Cajanek L, Yang S, Bryjova L, et al
Proceedings of the National Academy of Sciences of the United States of America 2013;110(7):E602-10

Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct aspects of microglia proinflammatory transformation
Halleskog C, Dijksterhuis Jp, Kilander Mb, Becerril-ortega J, Villaescusa Jc, Lindgren E, et al
Journal of neuroinflammation 2012;9():111-

Positional differences of axon growth rates between sensory neurons encoded by Runx3
Lallemend F, Sterzenbach U, Hadjab-lallemend S, Aquino Jb, Castelo-branco G, Sinha I, et al
The EMBO journal 2012;31(18):3718-29

SFRP1 and SFRP2 Dose-Dependently Regulate Midbrain Dopamine Neuron Development In Vivo and in Embryonic Stem Cells
Kele J, Andersson Er, Villaescusa Jc, Cajanek L, Parish Cl, Bonilla S, et al
STEM CELLS 2012;30(5):865-75

Interactions of Wnt/beta-Catenin Signaling and Sonic Hedgehog Regulate the Neurogenesis of Ventral Midbrain Dopamine Neurons
Tang Mz, Villaescusa Jc, Luo Sx, Guitarte C, Lei S, Miyamoto Y, et al
JOURNAL OF NEUROSCIENCE 2010;30(27):9280-91

Transplantable midbrain dopamine neurons: A moving target
Villaescusa Jc, Arenas E
EXPERIMENTAL NEUROLOGY 2010;222(2):173-8

Wnt2 Regulates Progenitor Proliferation in the Developing Ventral Midbrain
Sousa Km, Villaescusa Jc, Cajanek L, Ondr Jk, Castelo-branco G, Hofstra W, et al
JOURNAL OF BIOLOGICAL CHEMISTRY 2010;285(10):7246-53

Cytoplasmic Prep1 Interacts with 4EHP Inhibiting Hoxb4 Translation
Villaescusa Jc, Buratti C, Penkov D, Mathiasen L, Planaguma J, Ferretti E, et al
PLOS ONE 2009;4(4):e5213-

The homeodomain transcription factor Prep1 (pKnox1) is required for hematopoletic stem and progenitor cell activity
Di Rosa P, Villaescusa Jc, Longobardi E, Iotti G, Ferretti E, Diaz Vm, et al
DEVELOPMENTAL BIOLOGY 2007;311(2):324-34

Clast4, the murine homologue of human eIF4E-Transporter, is highly expressed in developing oocytes and post-translationally modified at meiotic maturation
Villaescusa Jc, Allard P, Carminati E, Kontogiannea M, Talarico D, Blasi F, et al
GENE 2006;:101-9

Hypomorphic mutation of the TALE gene Prep1 (pKnox1) causes a major reduction of Pbx and Meis proteins and a pleiotropic embryonic phenotype
Ferretti E, Villaescusa Jc, Di Rosa P, Fernandez-diaz Lc, Longobardi E, Mazzieri R, et al
MOLECULAR AND CELLULAR BIOLOGY 2006;26(15):5650-62

Cup is a nucleocytoplasmic shuttling protein that interacts with the eukaryotic translation initiation factor 4E to modulate Drosophila ovary development
Zappavigna V, Piccioni F, Villaescusa Jc, Verrotti Ac
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2004;101(41):14800-5

Expression of Hox cofactor genes during mouse ovarian follicular development and oocyte maturation
Villaescusa Jc, Verrotti Ac, Ferretti E, Farookhi R, Blasi F
GENE 2004;:1-7

New splicing variants for human Tyrosine Hydroxylase gene with possible implications for the detection of minimal residual disease in patients with neuroblastoma
Parareda A, Villaescusa Jc, De Toledo Js, Gallego S
NEUROSCIENCE LETTERS 2003;336(1):29-32

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