Dr Neil Rodrigues
" A key component of a cancer stem cell is its ability to self-renew and therefore drive tumour growth."
Who are you?
I trained at Harvard and Oxford Universities and I was recently recruited as a Reader to Cardiff University from my lab in Boston, USA. Historically my research has focused on normal adult stem cell biology, with a particular interest in blood forming stem cells, also known as haematopoietic stem cells. More recently my work has focused on how normal biology is disrupted in the context of cancer and the development of cancer stem cells which drive tumour growth.
Tell me about your research
My lab is interested in a transcription factor called GATA2. Transcription factors are involved in activating gene expression in cells and are therefore a central regulatory component of cell behaviour. GATA2 regulates hematopoietic stem cell behaviour and is also a very important regulator of some mature blood compartments, for example myeloid progenitor cells.
Dysregulation of GATA2 expression in blood stem cells can corrupt blood cell production. To this end, GATA2 has become implicated in the pathogenesis of two blood disorders/cancers: the pre-malignant condition myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). We know GATA2 is highly expressed in these settings, which confers poor prognosis for patients, but we don't know how this occurs mechanistically, what particular cell types in the bone marrow are involved or if we can target it therapeutically to improve treatment. So those are the questions that we want to answer.
How are you going to apply your work?
We want to very specifically compare pathways that GATA2 regulates in normal blood stem cells versus those that it regulates in cancer stem cells and see if we can identify and therapeutically target just those in cancer stem cells. We think we have a reasonable chance of doing this because GATA2 has different functions in different cell types so we should be able to identify some novel genes that are specific to cancer stem cell function.
What do you think cancer stem cells are?
For the two blood disorders that I work on, MDS and AML, the definition is quite clear cut. I think a cancer stem cell is a cell type that needs to able to self-renew so that it can drive tumour growth. Others characteristics such as their rarity and dormant status are more controversial.
Why do you think they're interesting?
It's very simple actually. They're the cells which drive tumour growth. So if you can therapeutically target the root cause of the tumour you can get rid of the tumour.
What are you up to today?
Well, I've got a meeting with my PhD student, who's just started in the New Year. He's funded by the Welsh Government as part of the Sêr Cymru National Research Network, working on novel therapeutic compounds to target cancer stem cells and improve stem cell based therapy. Other than that, it's looking through grants and general admin work today.
What can you gain from working here at the Institute?
It's a very rich scientific environment. There's a nice interactive network of investigators working on lots of different cancer types, which means you get different perspectives on what each other thinks about cancer stem cells.
There is a difference between solid cancers and liquid (blood) cancers, which I work on. But there are some commonalities and here I get the chance to apply findings of my colleagues to my work and vice versa.
(Interviewer: Sophie Hopkins, final year Biosciences undergraduate student)