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Determining Genetic Bases of Differential Response to Antipsychotics Using Patie...

Determining Genetic Bases of Differential Response to Antipsychotics Using Patient-Derived Neurons Schizophrenia (SCZ) affects 20 million people worldwide and antipsychotics remain the only effective pharmacological intervention. However, one-third of people with SCZ do not respond to first-line antipsychotic drugs. In the abse... ver más

31/12/2025

HVL

308K€

Presupuesto del proyecto: 308K€

Líder del proyecto

HOGSKULEN PA VESTLANDET No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-12-07

HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2021 ExpectedOutcome:

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No hay información privada compartida para este proyecto. Habla con el coordinador.

3 Participantes

HVL

307.94K€ | Lider

YALE UNIVERSITY

N.D. | Participante

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Duración del proyecto: 36 meses Fecha Inicio: 2022-12-07
Fecha Fin: 2025-12-31

Líder del proyecto

HOGSKULEN PA VESTLANDET No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 308K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Schizophrenia (SCZ) affects 20 million people worldwide and antipsychotics remain the only effective pharmacological intervention. However, one-third of people with SCZ do not respond to first-line antipsychotic drugs. In the absence of clinical biomarkers to stratify SCZ subtypes, all individuals receive the same initial intervention, and it takes >4 years on average before people with resistant forms of the condition receive suitable treatment. My overall aim is to unravel the pre-symptomatic cell-type-specific genetic circuits contributing to differential treatment response in SCZ. To achieve my aim I will use an interdisciplinary approach that improves my technical and soft skills and further extends my international network through a two-year stay at Yale University, and three months secondment at Harvard Medical School. During the return phase, I will establish myself as an independent researcher and a suitable candidate for leadership of a to-be-established stem cell lab at the host institute. Objectives are (O1) to identify cell-type-specific neuronal pathways associated with distinct neurotransmission imbalances in each SCZ subgroup using a human-based neurodevelopmental model. (O2) To determine the functional link between SCZ-associated risk variants and response to antipsychotics. Method: I will couple advanced stem cell models (region-specific brain organoids) with single-cell RNA sequencing to generate cell-type-specific transcriptomic profiles of patient-derived brain organoids from treatment-responsive and treatment-resistant forms of SCZ. I will integrate the potential risk variants from SCZ-GWAS and use published functional genomics data to determine the genetic pathways and associated regulators implicated in the etiopathophysiology of differential response to antipsychotics. Impact: identify distinct genetic makeup for each SCZ subgroup to serve as potential predictive biomarkers and points of therapeutic intervention.

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