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Natalia Pinello: RNA 5-hydroxymethylation in Haemopoiesis and Leukaemia

RESEARCH TYPE
T1,T2
PROGRAM
Flagship 3 Scholarships & Awards
TAGS
STATUS
In Progress

My project will characterise the role of RNA modifications in normal bone marrow development and acute myeloid leukaemia, focusing on understanding how epigenetic drugs work and exploring new targets.

The proposed project aims to advance the current understanding of the role of RNA modifications (epitranscriptomics) in normal biology and leukaemia. To date, azacytidine (5-AZA) is the only drug with proven survival benefit in myelodysplastic syndrome, the premalignant precursor to AML. Although it is known that 80 to 90% of 5-AZA is incorporated into RNA, the vast majority of studies are focused on its consequences on DNA, and therefore the therapeutic implications of the effect of 5-AZA on RNA have not been addresed. Through cutting-edge techniques such as sequencing of RNA in which these modifications are enriched, genes and pathways regulated by RNA modifications will be studied. This will reveal new insights into the therapeutic action of a drug already widely used in treatment of haematological malignancies. This project inhabits the T1T2 space, aiming to take basic science research and apply it in the clinic. The use of relevant in vitro models of human disease, our valuable pre- and post-treatment patient samples, and focus on a clinically approved drug (5-AZA), all in the context of our strong basic science RNA biology Program and our diverse clinical collaborations, provides a multipronged approach that will enable rapid translation of our findings.

 

Scholarship Awarded:

  • Name: Natalia Pinello
  • Member Group: Centenary Institute
  • Year and Duration: 2019 for 3 years
  • Amount: Full Award $78,864

 

5 Minutes with Natalia

 

Natalia Pinello  | 

Why did you decide to undertake a PhD in this area?

In the last 2 years, our lab (the Epigenetics and RNA Biology Program at Centenary Institute) became fascinated with RNA modifications and their role in the regulation of gene expression. This emerging field (epitransriptomics) builds on foundational work done on DNA and histone modifications (epigenetics), which led to the discovery of several epigenome-targeting drugs that are currently approved, or are in clinical trials, for cancer treatment. I decided to do a PhD in epitranscriptomics when I realised that understanding the molecular mechanisms that regulate RNA modifications would be pioneering work with great potential to open new therapeutic avenues for treatment of human diseases. My PhD research will focus on developing our understanding of the role of RNA modifications, specifically RNA 5-hydroxymethylation, in haemopoiesis and leukaemia.

 

 

Why is your research important in the context of Sydney Catalyst and translational cancer research? 

By improving our understanding of the role that RNA modifications play in normal and malignant haemopoiesis, my research has the potential to reveal the underlying therapeutic mechanisms for existing epigenetic therapies, as well as identifying novel potential targets. This would have immediate implications on current treatments, aligning with Sydney Catalyst's mission to improve the outcomes of those affected by cancer.

 

How do your family and friends feel about your PhD? Do they understand what you do?

My family and friends are all very happy and proud of me after hearing I was granted a Sydney Catalyst Full Scholar Award that will allow me to realise my dream of pursuing a PhD. They understand the value and essential role of research in unlocking the mechanisms of disease for identifying cures and improving quality of life. I am often sked how things are going in the lab and what exciting projects I am working on, and I love to tell them all about how my cells are going!

 

What are your plans once you graduate?

Epitranscriptomics is a novel and promising field, after completing my PhD I would like to pursue  post-doctoral position in a lab where I continue learning and progressing my research in this area. My ultimate goal is to become and independent group leader and be able to drive my own program and inspire other researchers. 

 

If you could be anywhere in the world right now, where would you be?

I would be in Aguas Dulces ("Sweet Water"), a small seaside village on the eastern coast of Uruguay.

 

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