Awarded Grants

Awarded Grants

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Spatial profiling of scRNAseq signatures in human parathyroid glands

Julie Ann Sosa

University of California at San Francisco

$50,000

Awardee: Julie Ann Sosa

Institution: University of California at San Francisco

Grant Amount: $50,000

Funding Period: April 1, 2021 - March 31, 2022

The objectives of this project were to: (1) utilize transcriptomic methods to define individual cell types within the human parathyroid, and (2) employ digital spatial profiling to visualize the localization of these cell types within the native parathyroid gland architecture. The developmental pilot phase work supported by the grant enabled us to establish a solid foundation of procedural optimization and proof of concept data for scaling our single cell sequencing efforts to a larger, more broadly representative cohort of donor parathyroid glands. 

 

The scientific objectives completed during the one-year project period are essential for comprehensive mapping of the human parathyroid gland.  The specific landmarks achieved include: demonstration that our live organ procurement work flow preserves tissue viability and maintains intact biochemical function; validation of recovery efficiency, parathyroid marker expression and cellular integrity in suspension; comparative assessment of whole cell vs nuclear isolation for downstream molecular analysis; validation of a novel split-pool sequencing approach that greatly improves capture efficiency, reduces selective recovery bias, and eliminates library construction batch effect concerns; digital spatial profiling of archived normal parathyroid gland sections to demonstrate the capture and whole transcriptome interrogation of specific cellular subsets demarcated by marker gene expression; and the molecular data from these studies showing that the cellular composition and transcriptional profiles of parathyroid gland tissue are dynamic rather than static.  This last finding reveals that the cellular content and biochemical activity of the parathyroid gland may be physiologically conditional, suggesting that functional reconstitution of the parathyroid gland is not a fixed target, but instead requires complementation of adaptive capacity in addition to terminally differentiated cellular phenotypes.  These key data will inform future and ongoing studies to reconstitute native parathyroid gland function.

Publication:

Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency

Chia-Ling Tu, Wenhan Chang, Julie A Sosa, James Koh

PNAS Nexus, Volume 2, Issue 3, March 2023, pgad073

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Nucleic acid binding by ZC4H2

Daniel Dominguez, PhD

UNC at Chapel Hill

$50,000

Awardee: Daniel Dominguez, PhD

Institution: UNC at Chapel Hill

Award Amount: $50,000

Funding Period: January 1, 2021 - December 31, 2021

Summary:

Mutations or genetic rearrangements in the protein, ZC4H2, cause a group of X-linked neurodevelopmental disorders for which there are no treatments. While the importance of this protein is clear, the specific function of ZC4H2 is still unknown. ZC4H2 is predicted to be a zinc-finger protein. We hypothesize that like many other zinc-finger proteins, ZC4H2 directly binds DNA or RNA, and functions to regulate gene expression programs required for normal development. Our goal is to determine if ZC4H2 interacts with nucleic acids and to identify specific genes and/or gene expression pathways that become dysfunctional when ZC4H2 is mutated. Patients suffering from ZC4H2-associated rare disorders have little recourse; understanding the biological function of this protein is a critical and necessary first step to uncover potential therapeutic approaches. 

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