14.00-14.15  Laura Mara Mueller, Max Delbrück Center for Molecular Medicine, Berlin, Germany
“Study of novel molecular defects in human pancreas dysfunction”

Unelucidated forms of monogenic diabetes, arising from rare mutations in one single gene, represent invaluable models for identifying new targets of pancreatic β-cell development and function. My PhD project focuses on putative disease-causing mutations identified by next-generation sequencing of a large cohort of patients with puberty-onset diabetes. By combining directed human induced pluripotent stem cell (iPSC)differentiation with gene editing, I generated a platform to investigate the role of the gene candidates and mutations in pancreatic cell fate decisions and cell function.

14.15-14.30  Rebecca Lea, The Francis Crick Institute, London, UK
“Identifying novel regulators of human pluripotency and embryogenesis” 

The mode of specifying pluripotent human epiblast (hEPI)is unclear and may differ from the mouse. Recent advances in single-cell techniques have allowed investigation of gene and transcriptional networks in human pre-implantation development. Numerous transcription factors (TFs), including KLF17, VENTX and ARGFX, are enriched in hEPI, upregulated in “naïve” hESCs, but absent in mouse blastocysts. I am investigating the role of theseTFs in pluripotency in hESCsthrough both loss- and gain-of-function studies, aiming to define human-specific pluripotency regulators acting in vitro and in vivo.

14.30-14.45  Ralitsa Madsen, University of Cambridge, UK
“Dosage-dependent effects of class IA phosphatidylinositol 3-kinase (PI3K) activation in human pluripotent stem cells”

Activating mutations in PIK3CA (catalytic class IA PI3K subunit) are frequent in cancer, and in isolation cause developmental overgrowth disorders. To understand the effects of PIK3CA mutations in a developmental context, we used CRISPR to knockin the strongly activating PIK3CA variant H1047Rinto one or both PIK3CA alleles ofhuman induced pluripotent stem cells.Collectively, we describe the first human developmental models of graded, endogenous PIK3CA activation, and reveal previously unappreciated dose-dependent effects on stemness.


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