Skip to Content
Exit Menu
Dr Cristina Pina

Dr Cristina Pina
Lecturer in Biomedical Sciences

Research area(s)

EPIGENETIC AND TRANSCRIPTIONAL MECHANISMS OF CANCER EVOLUTION

Research Interests

I am a clinically-trained research scientist working in the field of cancer epigenetics. I am fascinated by the mechanisms through which cells diversify their molecular composition1-2, and consequently vary their morphology and their function, to make organs, regenerate tissues, and produce tumours. While some of those diversification mechanisms rely on genetic mutations, others explore the way in which cells read their genes to produce the RNA and proteins that underlie cell function. The latter are referred to as epigenetic mechanisms.

My research is focused on understanding and manipulating epigenetic mechanisms to alter cell identity, and in particular, it aims to probe their role in cancer evolution in an attempt to unveil new therapies

In my lab, we study Acute Myeloid Leukaemia (AML), which is the most common acute leukaemia in adults. It has a dismal prognosis (<30% 5-year survival), particularly in elderly patients (<10%), who are most affected by the disease3. AML relies on epigenetic mechanisms for initiation and progression, and there is suggestive evidence that diversification of epigenetic mechanisms and molecular composition of AML cells can affect disease evolution in a manner akin to, but independent from, genetic mutations4.

We explore: (1) how individual epigenetic regulators modify activation of gene loci and their RNA production; (2) how their activity promotes or hinders molecular diversification, and (3) how this diversification modifies AML initiation, progression and response to therapy. We use a combination of genetic mouse models, human patient samples and next-generation sequencing, and perform functional assays and transcriptional analysis at the single-cell level, to track and manipulate AML cell diversification.

We have recently shown that Kat2a, a histone acetyl-transferase that activates transcription, controls frequency of locus activation and limits molecular diversification to maintain AML stem-like cells5, as well as pluripotent embryonic stem cells6, and may constitute a novel therapeutic target in AML7. We are currently extending these studies to other malignancies and different stages of disease progression, as well as probing the effect of molecular diversification control on cell identity and cell function through remodelling of gene-to-gene interactions in regulatory networks8-9.

In other lines of research:

(1) We investigate the cross-talk between DNA and histone modifications and the underlying metabolic pathways, and their contribution to leukaemogenesis and transcriptional activity.

(2) We model infant AML to understand the distinct mutational composition of AML that develops before and after the 1st year of life, and how this is influenced by intrinsic (epigenetic), as well as extrinsic (e.g. signalling) mechanisms.

1 Moris, Pina & Arias, Nat Rev Genet 2016 doi: 10.1038/nrg.2016.98; 2 Pina et al, Nat Cell Biol 2012 doi: 10.1038/ncb2442; 3 Liesveld, Leuk Res 2012 doi: 10.1016/j.leukres.2012.08.006; 4 Li et al, Nat Med 2016 doi: 10.1038/nm.4125; 5 Domingues et al, eLife 2020 doi: 10.7554/eLife.51754; 6 Moris et al, Stem Cells 2018 doi: 10.1002/stem.2919; 7 Tzelepis et al, Cell Rep 2016 doi: 10.1016/j.celrep.2016.09.079; 8 Pina et al, Cell Rep 2015 doi: 10.1016/j.celrep.2015.05.016; 9 Teles et al, PLoS Comput Biol 2013 doi: 10.1371/journal.pcbi.1003197

Research grants and projects

Grants

Combinatorial Effects of Histone and DNA Methylation in Acute Myeloid Leukaemia
Funder: British Society for Haematology
Duration: March 2020 - February 2021

Early Stage Research Set-Up Grant

The Role of Genetic, Epigenetic and Transcriptional Heterogeneities in Pre-leukaemia to Leukaemia Progression in AML
Funder: Lady Tata Memorial Trust
Duration: October 2017 - September 2020

PhD Studentship to Shikha Gupta (University of Cambridge)

Mechanistic Investigation of Histone Acetyl-transferase KAT2A in Acute Myeloid Leukaemia
Funder: Rosetrees Trust
Duration: April 2017 - March 2020

PhD studentship to Liliana Jesus Arede (University of Cambridge)