Harry G. Leitch

Reduced PDE4D expression and activity in Acrodysostosis Type 2 patient fibroblasts underlie disease pathology

This study shows reduced PDE4D expression and activity in ACRDYS2 patient fibroblasts, leading to altered cAMP/PKA signaling and compensatory changes in PDE4B.

A scalable and equitable framework for target and patient prioritisation in rare disease antisense therapeutics

The paper presents a framework for prioritizing targets and patients for antisense oligonucleotide therapies in rare diseases, focusing on equitable and systematic decision-making.

High resolution multi-scale profiling of embryonic germ cell-like cells derivation reveals pluripotent state transitions in humans

This paper establishes a defined feeder-free system to convert human PGC-like cells to pluripotent stem cells, tracking transcriptional and epigenomic transitions using multi-omic analysis.

Primordial germ cell DNA demethylation and development require DNA translesion synthesis.

The paper shows that DNA translesion synthesis is essential for primordial germ cell development and DNA demethylation in mammals, linking DDR to fertility.

The PREGCARE study: Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

The paper presents a method to assess recurrence risk of de novo mutations in families using deep-sequencing and haplotyping, finding that 59% of DNMs had reduced risk below 0.1%.

Global regulatory transitions at core promoters demarcate the mammalian germline cycle

The paper identifies global regulatory transitions at core promoters during mammalian germline development, showing a shift from somatic to maternal promoter codes in oogenesis.

SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA

SLIC-CAGE enables high-resolution transcription start site mapping using nanogram-level total RNA, significantly reducing the required input compared to existing CAGE methods.

Signalling pathways drive heterogeneity of ground state pluripotency

This study shows that 2i conditions increase transcriptional heterogeneity in pluripotent stem cells, driven by signaling pathways and negative feedback loss.