Developing a spatiotemporal gene atlas in iMCD lymph node tissue to identify diagnostic biomarkers and therapeutic targets

Awardee: David Fajgenbaum

Institution: University of Pennsylvania

Grant Amount: $60,570.00

Funding Period: February 1, 2023 - January 31, 2024


Summary:

Human Herpesvirus (HHV)-8-negative, idiopathic multicentric Castleman disease (iMCD) is a deadly hematologic illness with an unknown etiology that affects individuals of all ages. Although the causes, key immune cell types, signaling pathways, and cytokines involved are poorly understood, a key hallmark of iMCD includes characteristic lymph node features that are used for diagnosis. Despite importance of these lymph node features as diagnostic criteria, the underlying biological mechanisms driving them are not well understood. In the proposed LOI, we will develop a single cell RNAseq/spatial gene expression atlas in iMCD lymph nodes to characterize cell subpopulations, identify cell-type compositional changes, infer intercellular communication networks, and interrogate dysregulated cell types/cell locations within disease tissue. By completing the proposed specific aims we will gain important insights into lymph node biology in iMCD and the thorough characterization of the inflamed tissue will help identify new biomarkers and uncover dysregulated cell types that may be contributing to disease pathogenesis and pathology.

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