# Center for Lupus Research > **NIH NIH P50** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $1,720,325 ## Abstract The Cooperative Center of Research Translation entitled “Center for Lupus Research” (CLR) and based at Weill Cornell Medicine and JAX/GM aims i) to advance the knowledge of pathways that contribute to the establishment and amplification of Systemic Lupus Erythematosus (SLE), ii) to identify molecular mechanisms responsible for failure to respond to standard of care (SOC) therapies, and iii) to develop assays and tools to monitor these dysfunctional pathways and stratify patients towards personalized therapies. Understanding major disease pathogenic drivers and identifying biomarkers to follow them in the clinical setting are highly significant goals to advance clinical trial design and ultimately personalized patient care. The proposed studies stem from our previous CORT cycle and build on our work uncovering both molecular heterogeneity and basic mechanisms contributing to the generation of immunostimulatory nucleic acids (NAs) in this disease. We now provide data supporting that erythroid cells are a novel source of mitochondrial NAs giving rise to myeloid cell activation and pro-inflammatory loops in children with SLE. In Project 1, we will dissect the basic mechanisms, pathogenic role and biomarker potential of this novel pathway. In Project 2, we will capitalize on the groundwork that we have developed over the past 4 years of this CORT cycle using next generation single cell (sc) transcriptional and epigenetic profiling as well as on our discoveries of novel gene splice variants expressed in SLE patient immune cells. Both projects will incorporate cutting- edge technologies and build upon our established expertise in immune profiling. The projects will be critically supported by collaborations with Clinicians, Molecular and Cellular Biologists, Computer Scientists and experts in Systems Immunology. The Administrative Core will organize and operate the Center, and assure communication and interactions among all members and collaborators. The Clinical Core will oversee patient enrollment and clinical assessment, clinical data collection and sample storage and distribution. Samples obtained via the Clinical Core will enable the Center scientists to work together and the CLR will ensure integration of clinical and laboratory data associated with samples across Institutions. The specific aims of the projects are i) to identify the upstream mechanisms leading to retention of mitochondria in SLE Red Blood Cells (RBCs); ii) to follow the presence of Mito+ RBCs and their upstream dysfunctional pathways in pediatric and adult SLE patients during flares and remissions to establish their value as biomarkers and a stratification tool; iii) to dissect the contribution of erythroid-derived mitochondrial NAs to SLE inflammatory loops; iv) to identify transcriptional markers of SOC resistance pathways at the single-cell level and to identify isoforms associated with disease severity and response to treatment; v) to define epigenomic signatures of SLE Diseas... ## Key facts - **NIH application ID:** 10404359 - **Project number:** 2P50AR070594-06 - **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV - **Principal Investigator:** Maria Virginia Pascual - **Activity code:** P50 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $1,720,325 - **Award type:** 2 - **Project period:** 2016-09-21 → 2027-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10404359 ## Citation > US National Institutes of Health, RePORTER application 10404359, Center for Lupus Research (2P50AR070594-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10404359. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*