Guest lecture by Cristina Pina | The Role of KAT2A in transcriptional noise and stem cell face in the context of leukaemia

Medical Priority Anemia
Auditorium Sanquin
Plesmanlaan 125
1066 CX Amsterdam
The Netherlands

Guest lecture by Cristina Pina MD PhD (Brunel University London, UK) 

Title: The Role of KAT2A in transcriptional noise and stem cell face in the context of leukaemia

Host: Arthur Svendsen

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Abstract: In my talk, I will present an overview of my lab’s work focusing on the contributions of transcriptional noise to leukaemia initiation and maintenance. By ablating classical noise regulator KAT2A in pre-leukaemia and leukaemia cells, we have shown that transcriptional noise promotes cellular diversification in a manner agnostic to the nature of cell fate acquisition. In the context of leukaemia, noise facilitates pre-leukaemia transformation but disrupts leukaemia stem cell maintenance, with stage-specific consequence for disease evolution. Surprisingly, we found that loss of KAT2A enhances transcriptional noise in ribosomal biogenesis programmes, which can partly recapitulate KAT2A effects on leukaemia. I will discuss KAT2A contributions to noise and leukaemia in the context of its 2 complexes, SAGA and ATAC. I will end by reviewing the consequences of KAT2A loss and enhanced noise for ES cell pluripotency and differentiation, and discuss transcriptional noise in 3D gastruloid models of development and blood specification. 

Biosketch: Cristina Pina is a Senior Lecturer in Biomedical Sciences at Brunel University London. Her research group is interested in contributions of transcriptional noise to normal and malignant cell fate decisions, with a focus on the haematopoietic system.

Cristina trained in Medicine in Lisbon, Portugal, gained a DPhil in Clinical Medicine from the University of Oxford in 2008, and did post-doctoral work at UCL and the University of Cambridge. In her formative years she was mentored by Tariq Enver and Brian Huntly. During her PhD and post-doctoral work, Cristina pioneered the use of single-cell transcriptomics in the haematopoietic system to propose that cells take multiple alternative routes into lineage commitment, a work that crystalised her interest in transcriptional noise.

From 2015 to 2019, Cristina was a KKLF Intermediate Fellow and a Leuka John Goldman Fellow in the Departments of Haematology and Genetics at the University of Cambridge, where she started her independent work into stage-specific contributions of transcriptional noise to leukaemia evolution. Cristina joined Brunel University London in 2019, where she continues to research transcriptional noise and its epigenetic regulation, namely histone acetylation and chaperone complexes. More recently, she has developed a 3D gastruloid model of blood development, which she is using to dissect mechanisms of haematopoietic stem cell specification and leukaemia transformation in utero.