Genetics, Gene Therapy & Genetic Disease
- Genetic reprogramming with stem cells regenerates glomerular epithelial podocytes in Alport syndrome
Podocytes are the rate-limiting glomerular cells for type IV collagen production, and horizontal gene transfer or cell fusion with stem cells regenerates the renal parenchyma in Alport syndrome.
- Altered myocardial lipid regulation in junctophilin-2–associated familial cardiomyopathies
Our studies revealed, for the first time, unique alterations in the cardiac lipid composition—including distinct increases in neutral lipids and decreases in polar membrane lipids—in mice with HCM and DCM were caused by distinct JPH2 variants.
- A comparative study of structural variant calling in WGS from Alzheimer’s disease families
We developed a flexible protocol to generate a high-quality deletion call set and a truth set of Sanger sequencing–validated deletions with precise breakpoints between 1 and 17,000 bp from whole-genome sequencing data in multiplex families with Alzheimer’s disease.
- Single variant, yet “double trouble”: TSC and KBG syndrome because of a large de novo inversion
Short-read genome sequencing identified an 87-Mb inversion in a patient with atypical Tuberous sclerosis. The inversion disrupts TSC2 and ANKRD11, resulting in dual diagnosis of TSC/KBG syndromes.
- Reduced myeloid commitment and increased uptake by macrophages of stem cell–derived HPS2 neutrophils
Our current work uses iPSC-derived neutrophils to unveil novel reasons for the neutropenia found in HPS2 patients. HPS2 iPSC-derived neutrophils have lower myeloid commitment, and are actively phagocytosed by macrophages present in the iPSC cultures or healthy donor macrophages.
- CLN3 deficiency leads to neurological and metabolic perturbations during early development
Cln3 CRISPR mutant zebrafish larvae display BMP depletion and accumulation of glycerophosphodiesters and cholesteryl esters at very early developmental stages, recapitulating key features of human CLN3 disease.
- USP27X variants underlying X-linked intellectual disability disrupt protein function via distinct mechanisms
This study uncovers mechanisms by which X-linked intellectual disability disorder 105 (#300984; OMIM) variants alter USP27X biology and function.
- Analysis of the indispensable RAD51 cofactor BRCA2 in Naganishia liquefaciens, a Basidiomycota yeast
Identification of the BRCA2 homolog in the Basidiomycota yeast Naganishia liquefaciens reveals the general attributes of fungal BRCA2 and its essential role in Rad51-mediated homologous recombination.
- Intrinsic deletion at 10q23.31, including the PTEN gene locus, is aggravated upon CRISPR-Cas9–mediated genome engineering in HAP1 cells mimicking cancer profiles
The unintended 10q23.31 deletion frequency rises in HAP1 cells stressed during CRISPR-Cas9 engineering, leading to aberrant molecular and cellular changes resembling common cancer patient deletions.
- DOCK1 insufficiency disrupts trophoblast function and pregnancy outcomes via DUSP4-ERK pathway
This study reveals that decreased DOCK1 in placental villi affects trophoblast function via the DUSP4-ERK pathway, providing insights into adverse pregnancy outcomes.