Dr Daniela Robles-Espinoza recently joined the Sanger Institute as an International Fellow. We spoke about her work into acral melanoma, a deadly form of skin cancer affecting people in Latin America.
Dr Daniela Robles-Espinoza was interviewed by Alison Cranage, Science Writer at the Wellcome Sanger Institute.
Milking a scorpion for its venom, to research anti-venoms, was one of the projects in Daniela’s undergraduate degree. Another was studying the genetic changes in cancer cells. She continued with the cancer research rather than the scorpions and now leads the Cancer Genetics and Bioinformatics Laboratory at the International Laboratory for Human Genome Research, National Autonomous University of Mexico, where she studies a deadly form of skin cancer. Daniela was also recently appointed as an International Fellow at the Wellcome Sanger Institute. We spoke to her about her current research on acral melanoma, a type of skin cancer that is very rare in Europe, but the most common in several countries in Latin America, Africa and Asia1.
Image: Dr Daniela Robles-Espionza, Credit: Wellcome Sanger Institute
Tell us about acral melanoma
Its name means that it occurs in extremities. It is a skin cancer that appears on the soles of the feet, the palms of the hands and under fingernails. It’s the most common type of melanoma in Mexico, as well as other countries in Latin America, Asia and Africa – but world-wide, it’s very rare. In Europe and Australia, cutaneous melanoma, caused by exposure to UV light, is much more common. We don’t know what causes acral melanoma, but it’s not UV light.
Why are you studying it?
We’ve got two main aims: to find out the cause, and to find out how to treat it. It’s not a type of cancer that has been studied deeply. The best treatment is immunotherapy, but even that isn’t as effective as it is on cutaneous melanoma. Plus, immunotherapy is expensive; it’s neither accessible nor affordable in Mexico. Most patients have chemotherapy, but less than one per cent of patients respond to that if they’re treated at a later stage – it just doesn’t work. Living here, you see it, and we can’t treat it. I want to change that.
How are you studying it?
All cancers are caused by changes, or mutations, in a cell’s DNA. Cancer mutations result in a cell dividing and growing uncontrollably. Researchers can uncover the specific mutations responsible for a cancer by comparing the genes or genomes of cancer patients.
Melanoma skin cancer is the 5th most common cancer in the UK, with about 16,200 new cases a year. Most of these are cutaneous melanoma, caused by exposure to UV light which damages skin cells DNA.2
Bob Marley died from acral melanoma in 1981.
We want to investigate this cancer’s genome to find out what causes it. We are looking at everything we can find in the genome and transcriptome, including which genes are active in the cells. We are looking at the genetic information together with characteristics of the cells – for example, if the tumour is ulcerated or not, or whether it has spread from the primary site. Currently, we’ve sequenced exomes – the parts of the genomes that code for proteins – and we’re planning to do whole genomes.
We’ve identified some candidate genes that might be associated with the cancer’s ability to metastasize, so the next step is to test this in the lab. We’re planning to use CRISPR technology to activate each candidate gene in cells – to see if it increases their metastatic potential. For this and other projects, we are working with Dr Patricia Possik at the National Cancer Institute in Brazil. We are able to send her patient tumour samples and these are inoculated into mouse skin. Then we can study the evolution of these tumours as they grow. We can also test potential therapeutics. We are also hoping to start these experiments shortly at our own institute.
Maybe it’s a dream, but I want to find out if there are other vulnerabilities in these types of cancer cells that mean we could cheapen the costs of current treatments, or that may translate into patients having another treatment option.
How did your research career start?
After my undergraduate degree in genomics at the National Autonomous University of Mexico, I moved to the UK to start a PhD at the Sanger Institute with Dr David Adams in the Cancer, Ageing and Somatic Mutations Programme. Working in the lab was not my strong point – I broke so many things – so I stuck with bioinformatics. That was when I started studying melanoma.
With Prof Julia Newton Bishop and Prof Tim Bishop, collaborators from the University of Leeds, I worked on a project to investigate the genomes of about 200 people affected by skin cancer without a known cause. We hypothesised that their cancers were likely to be genetic – because each person had a family history of the disease, but we didn’t know the precise mutations involved. Our analysis uncovered a gene, POT1, that was responsible. Now POT1 is included on diagnostic gene panels that test patients for the disease, so I hope that’s making a difference to a few families.
I stayed at Sanger and took up a post-doctoral research position, working with Dr Nicola Roberts. We used data from The Cancer Genome Atlas, focussing on the genomic changes in tumours that occur as cells grow, rather than those that are inherited from birth. We studied the MC1R gene, which is involved in producing the melanin pigment responsible for skin and hair colour. People with variants in this gene produce a more red-yellow melanin as opposed to black or brown. These variants result in melanin that is less good at absorbing UV light, and it also produces more ‘reactive oxygen species’, so cells are more at risk of DNA damage. We found that people with variants in this gene have more mutations in their skin cells, helping us to understand the mechanisms by which these tumours grow and their potential causes.
Tell us about setting up your research group
I’d kept in touch with the director, Dr Rafael Palacios, from my undergraduate degree. He was visiting London a few years ago and so we met to catch up. At the time he was founding an institute in Mexico and offered me a position to start a new research group in cancer genetics. It was a great opportunity. The University is world-class, and Querétaro City is beautiful. I didn’t take much convincing!
It hasn’t been easy. The main challenges are in logistics – I’ve set everything up from scratch to get skin samples from patients, then they are processed in various labs, then we sequence the genomes and then analyse the data. We’re getting samples from patients in several different hospitals – there is a lot of paperwork. But whenever I’m fighting a form that I need to fill in, I remember it’s for the greater good. It’s worth it.
Who inspires you?
Rafael Palacios – he’s really a driving force here. He’s done a lot for science in the country. He’s founded the institute here and created successful courses. He’s really visionary and inspiring to work with.
In the UK, David Adams at the Sanger Institute, plus Julia Newton Bishop and Tim Bishop at the University of Leeds.
It’s great to be able to continue my work and collaborations with both the Sanger and Leeds. Everyone is very supportive, and the melanoma research community is very welcoming. People share knowledge and resources. My fellowship at Sanger means that, once travel restrictions lift, I’ll be able to spend time in the UK to continue to learn from those people and build collaborations.
What are your plans for the future?
I would like to stay here and do my best to investigate the genomic profile and potential treatment options of types of cancer that are important in Mexico and Latin America, I think this is an area that is severely understudied. I am really happy to be part of the DERMATLAS project, as it will help substantially to support my research into the causes of acral lentiginous melanoma. I am also working with a team to investigate other types of cancer such as hepatocellular carcinoma, another important cause of death from cancer in Mexico. I definitely hope to be able to continue collaborating with researchers at the Sanger, it really makes all the difference in the world!
Find out more
2 – Statistics from Cancer Research UK, https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/melanoma-skin-cancer#heading-Three accessed on 09/03/21.