{"id":95498,"date":"2026-03-26T17:01:49","date_gmt":"2026-03-26T15:01:49","guid":{"rendered":"https:\/\/umfcluj.ro\/?post_type=crct&p=95498"},"modified":"2026-04-16T16:31:33","modified_gmt":"2026-04-16T13:31:33","slug":"deciphering-the-genetic-and-genomic-architecture-of-systemic-lupus-erythematosus","status":"publish","type":"crct","link":"https:\/\/umfcluj.ro\/en\/research\/research-projects\/pnrr-projects\/deciphering-genetic-genomic-architecture-systemic-lupus-erythematosus\/","title":{"rendered":"Deciphering the Genetic and Genomic Architecture of Systemic Lupus Erythematosus"},"content":{"rendered":"

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Project\u00a0title:\u00a0Deciphering the Genetic and Genomic Architecture of Systemic Lupus Erythematosus<\/strong><\/p>\n

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Contract no: 760280\/26.03.2024<\/strong><\/p>\n

Code: 199\/31.07.2023<\/strong><\/p>\n

Total budget:<\/strong> 6.131.326,45 RON, of which the amount of PNNR financing is 5.600.000 RON and the related VAT is 531.326,45 RON.<\/p>\n

Duration of project:<\/strong> 28 months (between 26.03.2024-30.06.2026)<\/p>\n

Project Director: <\/strong>Prof. dr . George Bertsias, University of Crete School of Medicine, Department of Rheumatology and Clinical Immunology, Crete, Greece.<\/p>\n

Postdoctoral researcher (UMF project manager):<\/strong> Asst. Univ. Dr. Pamfil Cristina, e-mail: cristinapamfil.umfcluj@gmail.com<\/a><\/p>\n

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The implementation place<\/strong>: University of Medicine and Pharmacy “Iuliu Ha\u021bieganu” Cluj- Napoca – Rheumatology Clinic Cluj-Napoca, Clinicilor street no. 2-4 and the Department of Medical Genetics, Pasteur street no. 6, Cluj-Napoca, Romania.<\/p>\n

Summary: <\/strong>Systemic Lupus Erythematosus (SLE) is a prototype autoimmune disorder that affects multiple organs. Despite advances in the disease understanding, there are numerous scientific and clinical unmet needs and patients experience substantial morbidity and reduced quality of life. Genetic contribution plays an important role in SLE with currently identified variants explaining <20% of heritability. Moreover, although SLE is characterized by augmented type I interferon (IFN) expression and\/or bioactivity, central to disease initiation and progression, the genetic drivers for this perturbation and inter-patient variability remain elusive. Notably, the IFN signature correlates with enhanced efficacy of biological treatments but the underlying molecular explanation is missing. Herein, and capitalizing on our experience with the clinical, genetic, and transcriptomic characterization of SLE, we will gain additional insights first, by integrating genotypes, genome-wide mRNA and alternatively spliced transcriptomes focusing on the IFN pathway, from our existing cohorts of >500 SLE and >300 healthy individuals. Next, we will purify plasmacytoid dendritic cells (main IFN producer) from SLE and healthy subjects, to undergo genotyping and transcriptome analysis at steady state and following activation, thus enabling to call cell-specific expression quantitative trait loci (eQTLs) contributing to IFN deregulation in SLE. Finally, we will analyse our cohort of >100 SLE patients under treatment with the biological agent belimumab (anti-BAFF mAb), in order to characterise in vivo eQTL interactions with the IFN status and BAFF blockade. Our top prioritized results from the aforementioned studies will be functionally confirmed with gene silencing\/editing assays in relevant primary immune cells. Collectively, our research will shed light on the genetic causality and aberrant IFN production in SLE, with implications for the molecular and clinical stratification of the disease.<\/p>\n

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General Aim<\/strong>: Our objective is to gain novel insights into the genetic basis of SLE by integrating genome variation with expression.<\/p>\n

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Specific Objectives: <\/strong><\/p>\n