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Nicolás Miguel Fissolo

I am biochemist and PhD in human biology. Since 2008 I work as a researcher at the clinical neuroimmunology - Multiple Sclerosis Center of Catalonia (Cemcat) research group. My activity is based on the study of multiple sclerosis, mainly in the identification of molecular biomarkers associated to different aspects of the disease.

Institutions of which they are part

Postdoctoral researcher
Clinical Neuroimmunology
Vall Hebron Institut de Recerca
Investigador/a postdoctoral
Multiple Sclerosis Centre of Catalonia
I graduated as a biochemist in 1999 from the University of Córdoba (Argentina). In 2005 I obtained a PhD in human biology from the University of Ulm (Germany) for my work in the DNA vaccine field. Afterwards, I carried out a 3-year postdoctoral stay at the Hertie Institut for Brain Research at the University of Tübingen (Germany) focused on the study of antigenic presentation in multiple sclerosis. In 2008 I joined the research group of the clinical neuroimmunology - Cemcat directed by Dr. Xavier Montalban where I have been working until now.

Since 2010 I have been working as principal investigator of several projects focused on the identification of new molecular biomarkers that allow the characterization of the different aspects of the disease, among which are included prognostic biomarkers in the initial phases of the disease, biomarkers of response to treatment, and biomarkers of disease activity.

Research lines

Research for therapeutic targets and/or therapeutic approaches

5.1 Bone morphogenetic proteins (BMP) antagonism as a target to enhance neuroregeneration in multiple sclerosis Lead scientist: Carmen Espejo Because MS therapies are mainly conducted to modulate the immune response, in the last years new research lines have been established in order to better understand the mechanisms that regulate and/or mediate the neurodegenerative and neuroregenerative processes. Although neuroregeneration occurs in the adult central nervous system (CNS), several negative signals impede the restore of the damaged CNS. Some of these signals could be mediated by BMPs, since these proteins have a key role in the developing CNS and in the adult CNS neurogenesis. BMPs also have a prominent role in the development of the thymus as well as in the differentiation of T-cells. We aim to characterize the expression of BMPs, receptors and antagonists in MS lesions, quantify them in the CSF of MS patients and evaluate its prognostic value. We also aim to test the therapeutic potential of the administration of BMP4 and an antagonist of BMPs, noggin, in experimental autoimmune encephalomyelitis (EAE), an experimental model of MS. 5.2. Role of semaphorins 3A and 7A in neuroregeneration and immune regulation in EAE model Lead scientist: Carmen Espejo As BMPs, Semaphorins could also be involved in neurodegeneration in MS, as negative signals impeding the restoration of the damaged CNS. This project aims to study the role of semaphorin 3A (sema3A) and sema7A, two axonal guidance molecules also involved in the regulation of immune responses, in EAE pathogenesis as well as their therapeutic implications. 5.3 Microbiota as a therapeutic target in multiple sclerosis: preclinical trial of two probiotics and butyrate in two experimental models of multiple sclerosis Lead scientist: Carmen Espejo A series of recent studies reveal that gut microbiome can influence immune responses distant from mucosal surfaces. Immunological dysregulation is the cause of numerous human disorders such as autoimmune diseases. Aberrant central nervous system (CNS) autoimmunity arises as a consequence of the lost of the normal immune tolerance to CNS self-antigens. Commensal microbiota affects the autoreactivity of peripheral immune cells to the CNS. The main objective of this project is to test whether the administration of two probiotics and butyrate has a beneficial effect in MS experimental model. 5.4. Tolerance induction in experimental autoimmune encephalomyelitis using gene therapy Lead scientists: Jordi Barquinero / Carmen Espejo Previous collaboration works with the group of Gene and Cell Therapy of our institution resulted in the development of a therapeutic strategy in which bone marrow cells were genetically modified to express a self-antigen with the aim to induce antigen-specific tolerance. We could see a therapeutic effect even in the absence of myeloablation, thus suggesting that a concrete population of cells generated in the cell culture, but not cells with a repopulating capacity, were responsible for the therapeutic effect seen in these mice. We have identified a candidate population, called myeloid derived suppressor cells that might be mediating the antigen-specific effect. 5.5. Genomic signature-based small molecule screening of neural stem cells to identify novel compounds to enhance oligodendrogenesis Lead scientist: Carme Costa Genomic signatures will be defined in the different stages of differentiation from neural stem cells to mature oligodendrocyte. The signatures will be used to identify new drugs that could induce oligodendrogenesis. In vitro validation will be performed to confirm that the addition of these compounds to cells under different stages of lineage commitment produces the desired gene expression signature. The selected compounds will be finally tested in vivo, in an experimental autoimmune encephalomyelitis mouse model. 5.6. Neurodegeneration and neuroregeneration in multiple sclerosis: search of biomarkers and potential new therapies Lead scientist: Nicolás Fissolo MS is a disease with two components: an inflammatory component that prevails in the initial stages (relapsing-remitting), and a neurodegenerative component that is more prominent in the advanced stages of the disease (progressive). Currently, therapeutic strategies in MS are highly effective to reduce or even suppress the inflammatory component of the disease; however, current treatments have proven to be totally ineffective in those patients in whom the neurodegenerative component predominates. Despite numerous studies in this field, the mechanisms of neurodegeneration that take place during the course of the disease are not well understood. We aim to identify biomarkers and potential therapeutic targets in the neurodegeneracion and neuroregeneration events taking place during the course of the EAE, the animal model of MS. 5.7 Targeting astrocytes to prevent neurodegeneration in patients with multiple sclerosis Lead scientist: Manuel Comabella The main objective of this proposal is a pharmacological modulation of astrocyte function in order to influence and modify neurodegeneration in MS patients.

IP: Nicolás Miguel Fissolo , Carmen Espejo Ruiz, Herena Eixarch Ahufinger

MRI measures of neurodegeneration in Multiple Sclerosis - Clinical implications

Lead scientist: Jaume Sastre-Garriga / Deborah Pareto Brain volumetry is about to take a central role in the management of patients with MS. Recent evidence suggests that the neurodegenerative process can be reliably estimated in vivo with the help of MRI and appropriate software tools, and that such measurements are clinically relevant both for prognosis as well as in monitoring of treatment response. In the Clinical Neuroimmunology Group, brain volumetry estimates have been already obtained using well-tested methodologies in selected cohorts and its clinical relevance has been confirmed. New, more sophisticated software tools to obtain in-depth measuring of brain and spinal cord areas are now being tested for clinical relevance. This has been achieved through collaboration with the MRI Unit at the Institut de Diagnòstic per la Imatge.

IP: Manuel Comabella Lopez, Carmen Espejo Ruiz, Jordi Barquinero Mañez, Nicolás Miguel Fissolo

Projects

Search of immune signatures associated with multiple sclerosis disease phenotypes

IP: Nicolás Miguel Fissolo
Collaborators: Clara Matute Blanch, Merce Bonastre Garcia, Luciana Midaglia Fernandez, Breogan Rodriguez Acevedo
Funding agency: Instituto de Salud Carlos III
Funding: 169400
Reference: PI20/00276
Duration: 01/01/2021 - 31/12/2023

Identificación de proteínas relacionadas con el envejecimiento en pacientes con esclerosis múltiple progresiva y estudio de su potencial efecto neuroreparador en modelos animales.

IP: Nicolás Miguel Fissolo
Collaborators: Clara Matute Blanch, Luciana Midaglia Fernandez
Funding agency: Instituto de Salud Carlos III
Funding: 102850
Reference: PI17/00596
Duration: 01/01/2018 - 30/06/2022

Neurodegeneración y neuroregeneración en esclerosis múltiple: búsqueda de biomarcadores y posibles nuevos tratamientos

IP: Nicolás Miguel Fissolo
Collaborators: Angela Vidal Jordana
Funding agency: Instituto de Salud Carlos III
Funding: 69575
Reference: PI13/00401
Duration: 01/01/2014 - 30/06/2018

Immunogenicity: assesing the clinical relevance and risk minimization of antibodies to biopharmaceuticals. IMI Grant Agreement nº 115303

IP: Manuel Comabella Lopez
Collaborators: Carmen Tur Gomez, Xavier Montalban Gairín, Nicolás Miguel Fissolo
Funding agency: The Innovative Medicines Initiative
Funding: 464328
Reference: ABIRISK_IMI2010
Duration: 01/03/2012 - 27/02/2018

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