Getting to know Dr. Maria Joao

  • Dra. Maria Joao Baptista

Dr Maria Joao Baptista

She’s a researcher from the Josep Carrreras Leukaemia Research Institute (Campus ICO-GTiP)

Age: 41

Place of birth: Porto (Portugal)

Mini curriculum

I studied pharmacy in Porto and I was an Erasmus student in Madrid, the first Spanish city I lived in. I went back to Porto and did a Master’s degree in oncology and started working in the field of hematology. Having finished my dissertation I did a doctoral course in Salamanca under the supervision of Prof. Alberto Orfao. I moved to Barcelona in October 2005 to write my doctoral thesis under the supervision of Prof. Emili Montserrat and Dr. Francesc Bosch at the Hospital Clínic. At that time I devoted my full attention to research into B-cell lymphoproliferative syndromes.

It was just when the practical part of my thesis was drawing to an end that I started working at the Josep Carreras Leukaemia Research Institute. It was difficult to start off with because I was writing my thesis and, at the same time, I had embarked on this great IJC project. I was one of the first researchers at the Institute and that is something I’m very pleased about. I very much appreciate the IJC’s confidence in me and I very much hope to be able to fulfil expectations!

4 words to define you:

Persistent, methodical, demanding, creative. 

– You have recently published a scientific paper entitled, “Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics”. What is it about?

The paper is about a study of the role of the NKX2-3 protein in the development of lymphomas. It all started upon the observation that some patients with marginal zone lymphoma express NKX2-3 in an augmented way. Transgenic mice are produced that express NKX2-3 and it can be observed that these mice develop tumours similar to those of patients with marginal zone lymphoma. It is therefore thought that the overexpression of the NKX2-3 protein might play an important role in the appearance of these lymphomas. To reveal the role of the NKX2-3 protein in the development of these lymphomas various experiments have been undertaken, from which it can be concluded that NKX2-3 induces B-cell receptor pathway signalling, and they have also made it possible to identify the various proteins involved in the process and their respective effects on survival, proliferation and migration. 

– Could you tell us, in terms a layman can understand, about the research you are doing at the IJC?

There are a number of projects underway in our group and almost all of them are focused on aggressive lymphomas in patients with HIV. These patients present a greater incidence of lymphomas than the rest of the population on account of HIV depressing the immune system. From the hematological point of view it is possible, at the present time, to treat these patients in the same way as patients who are not infected with HIV and the responses to treatment for the lymphoma are identical. However, as occurs with patients who are not infected with HIV, there are some who do not respond to standard treatments, and others whose response is short-lived. Furthermore, lymphomas in patients with HIV tend to be more aggressive and, at the biological level, the tumour cells are exposed to other factors. In the lymphoid neoplasia group we are looking for markers that will enable us to identify patients that might not respond to standard treatments, or have only short-lived responses. We are also trying to understand the differences there are between patients who are infected with HIV and those who are not.

– Why did you focus on the study of lymphomas?

I suppose I could say it happened by chance. The first research work I did, when I was doing my Master’s in oncology, was the study of T lymphocyte and NK cells. When I was in Salamanca I started studying lymphoproliferative syndromes, and lymphomas are in this group of hematological diseases. From there, my doctoral thesis and my work at the IJC have continued along those lines.

– Let us assume that a 41-year-old-woman is diagnosed as having diffuse large B-cell non-Hodgkin lymphoma and that she is also infected with HIV. What is the difference between her being diagnosed today in comparison with what would have been the diagnosis 25 years ago?

The HIV virus was only discovered 33 years ago (1983) so 25 years ago the treatments available for HIV were not very effective and patients with HIV did not have a very long life expectancy. At that time attention was focused on combating HIV rather than on the lymphoma. HIV was a devastating disease and when a lymphoma was diagnosed in such patients their general condition was a very delicate one. When possible, chemotherapy was applied for the lymphoma but the associated complications were very frequent and this led to the dosage being reduced and long pauses between cycles of treatment. The results obtained were correspondingly disappointing. In this regard we must applaud the progress that has been made in research into HIV, thanks to which, these days, patients infected with HIV are treated in the same way as patients who are not infected. 

  • Maria Joao José Tomás Navarro

Dr. Maria Joao with Dr. Tomás Navarro, lead researcher at the IJC lymphoid neoplasms research group.

– How would you describe a research centre like the IJC? Why is it interesting?

The IJC is a centre specifically for research into leukaemia. As such, it is quite unique in the world. There are great advantages in bringing different researchers together, all of them devoted to the study of different kinds of leukaemia and other malignant blood diseases, because it facilitates the exchange of information and experience. The IJC has other interesting aspects, the fact, for example, that it is spread over three campuses, each of which is near a major hospital.

– What is your working day like?

I think I spend my days like most of my colleagues. There isn’t much time for activities outside the world of work. Basically I spend my time in the laboratory.

– What do you most and least like about your work?

What I most like about my work is being able to study and to be constantly learning. Every day is a challenge and there is something new all the time. Routine is something that does not exist in the life of a researcher.

What I least like is the way in which research is funded and the way it is regarded by society. Everyone recognises the effort involved, but the life of a researcher is a precarious one. Society comforts itself by thinking our work is a vocation. Yes, it is a vocation, like many others, but that does not mean that we have to do our work, develop our projects and eke a living on the basis of grants.

I spend a great deal of my time in summarising projects for calls to tender for grants, filling in forms, ticking boxes. There is a great deal of bureaucracy involved in the whole process and it is a difficult process because the percentage of projects that are awarded funding is a small one. 

Annual Activity Report 2015

Here you can read the Annual Acivity Report. 

Find out about who we are -our mission, vision and values and who are part of our Unstoppable team-, our lines of work and who has helped us to make our work possible in 2015.

You can read it online:

You can also dowload it HERE.

Dr. Norma Gutiérrez, expert in multiple myeloma, visits the Josep Carreras Leukaemia Research Institute

  • Dra Norma Gutiérrez

The Josep Carreras Leukaemia Research Institute (IJC) recently had the pleasure of receiving a visit from Dr. Norma Gutiérrez at the Catalan Institute for Oncology/Germans Trias i Pujol Campus. Dr. Norma Gutiérrez is associate doctor in hematology at Salamanca hospital and lead researcher in the Multiple Myeloma Group at the Biomedical Research Institute of Salamanca (IBSAL).

Her main area of research is focused on understanding the genetic basis and pathogenesis of multiple myeloma and other monoclonal gammopathies using high-performance genomic technologies and functional trials. She also coordinates the cytogenetics studies of the Spanish Myeloma Group. She has published more than 140 original articles in international journals.

In her spare time Dr. Gutiérrez likes reading and walking.

Dr. Gutiérrez gave a paper at our campus entitled, Genomics in Multiple Myeloma.

We wanted to ask Dr. Gutiérrez to tell us more about the current challenges in multiple myeloma.

● Dr. Gutiérrez, what does it mean to be diagnosed with multiple myeloma?

Multiple myeloma (MM) is a hematological cancer that affects plasma cells located mainly in the bone marrow. These cells are the ones that produce immunoglobulins or antibodies. In multiple myeloma the tumorous plasma cells produce large numbers of the same monoclonal antibody and these can be quantified in the blood and sometimes in the urine. The accumulation of tumorous plasma cells and the excessive production of monoclonal antibodies causes damage to various organs such as the bones and kidney leading to the symptoms that characterise this cancer.

Myeloma must be distinguished from a benign process called monoclonal gammopathy of undetermined significance (MGUS), which occurs in approximately 1% of the general population and in 3% of healthy people over the age of 70. Although monoclonal antibodies and abnormal plasma cells are detected in MGUS, they do not cause any damage to the organism and consequently require no treatment. Nevertheless, it requires constant monitoring because with the passage of time there is a risk of it turning into myeloma.

● What treatments currently exist for patients diagnosed as having multiple myeloma?

Until recently treatment for multiple myeloma has been based on combinations of chemotherapy, which almost always includes melphalan and steroids. At the present time there are new drugs with mechanisms of action that are different from those of chemotherapy and these have improved response levels and prolonged patients’ lives. The most notable of these are the proteasome inhibitors such as bortezomib and immunomodulatory drugs such as lenalidomide. The initial treatment is generally based on the combination of three drugs depending on the age of the patient given that with patients under the age of 65 high doses of chemotherapy are indicated followed by a transplant of hematopoietic progenitors. 

  • Cèl·lules mieloma múltiple

● Over the last 10-15 years biological therapies have made great progress and have lengthened the periods in which multiple myeloma patients can be free of the disease. How do you think current therapies can be improved even more?

Exactly, there has been a significant increase in the number of options for treatment over the last 10 years. Such advances are key in a cancer such as myeloma, the natural course of which is characterised by successive relapses. There are a number of drugs, from new generations of proteasome inhibitors and immunomodulatory agents to monoclonal antibodies against the blood cells’ own antigens which enable relapses to be successfully treated and periods free of the disease lengthened.

But we are still far from using the therapeutic arsenal at our disposal appropriately. We have known for a long time that the evolution of patients with myeloma is very uneven, probably due to the fact that the biological characteristics of the cancerous plasma cells vary greatly from patient to patient. It can be assumed that the efficacy of drugs will be different depending on whether the cellular processes they modify are critical or not for a particular myeloma. So I think one way forward in rationalising the way drugs are currently used is to design trials, involving biological studies of cancerous plasma cells, that are far more ambitious than those we are accustomed to in order to determine what characteristics differentiate the myelomas that respond from those that do not.

● Your area of specialisation is focused on understanding the disease’s genetic basis. What do you think is the most important discovery made by your team with regard to the study of myeloma?

Given that the knowledge about the genomic basis of multiple myeloma that we have contributed is of modest proportions the most outstanding thing is probably to have observed, using advanced genomic techniques, that the clonal plasma cells of pre-malign entities such as monoclonal gammopathy of undetermined significance have the same genomic alterations as multiple myeloma. Why, from the genomic point of view, some apparently similar cells are capable of provoking multiple myeloma in some cases yet remain in an asymptomaticprocess in others is still an enigma in this pathology.

● How can the study of genetics help in improving current treatments for multiple myeloma?

It is true that therapeutic developments sometimes follow very different paths from those of advances in knowledge about the disease’s biology, specifically, genomic alterations. In fact, the mechanisms of action often become apparent much after having demonstrated the efficacy of the therapeutic agent. Having said that, it is undoubtedly true that the more we know about the genomic characteristics of the myeloma cell the more progress we can make in curing this disease.

Thanks to unstoppable technological development we have methodologies available that enable us to study the flow of genomic information from the DNA to the RNA virus and the protein using very small samples. This was unthinkable only a few years ago. We have the tools, now we only need to be audacious enough to know how to use them to get into the inner workings of the cancerous plasma cells while avoiding the risk of sailing on the surface of a sea of disconnected genomic data.

● The Josep Carreras Foundation has established a research centre specifically for leukaemia and other malignant blood diseases, the IJC. What do you think the repercussions of this will be in the field of science and for society in general?

Not nearly enough is invested in research. I believe that with a research centre devoted entirely to malignant blood diseases it is possible to optimise resources and focus them towards more exhaustive studies of the biology of these diseases. I also think it makes it easier for researchers working at different levels to concentrate their efforts on resolving more specific and better defined problems, thereby avoiding dispersion, at least in part. I have had the opportunity to get to know the Institute and I think that the projects underway are really attractive. In time this Institute could become an international beacon in the field of hematology.

The effects on society are more difficult to evaluate. When people are healthy, initiatives such as this often go unnoticed. But when these diseases knock at their door their commitment to research is much stronger. I think progress has been made in this too and that most people appreciate and support investment in cancer research because they know that one way or another it has an effect on their health. 

Un millar de pacientes de leucemia de toda España sale a la calle para apoyar un proyecto pionero

• En nuestra campaña anual con motivo de la Semana contra la Leucemia (21-28 de junio), desde la Fundación Josep Carreras estamos intentando recaudar 150.000€ para un programa de investigación pionero en España. Ya llevamos recaudados más de 60.000€.

• 654 pacientes y sus familias se han unido hoy para hacer concentraciones en 48 provincias españolas y llamar a la solidaridad de los españoles.

• Los primeros resultados de esta técnica basada en inmunoterapia en Estados Unidos son muy prometedores. Un 85% de pacientes enfermos de leucemia linfoblástica aguda que no respondían a ningún tratamiento, están en remisión de la enfermedad.

• La Fundación ha invertido desde su creación más de 200 millones de euros en proyectos de investigación. En 2010 creó el Instituto de Investigación contra la Leucemia Josep Carreras (IJC) de la mano de la Generalitat de Catalunya. Es el primero de Europa en hacer investigación exclusiva sobre leucemia y otras enfermedades malignas de la sangre.

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La fábrica de células imparables: un proyecto pionero en nuestro país

  • En nuestra campaña anual con motivo de la Semana contra la Leucemia (21-28 de junio), desde la Fundación Josep Carreras intentaremos recaudar 150.000€ para un programa de investigación que todavía no se ha llevado a cabo en España.

  • Los primeros resultados de esta técnica basada en inmunoterapia en Estados Unidos son muy prometedores. Un 85% de pacientes enfermos de leucemia linfoblástica aguda que no respondían a ningún tratamiento, están en remisión de la enfermedad.

  • La Fundación ha invertido desde su creación más de 200 millones de euros en proyectos de investigación. En 2010 creó el Instituto de Investigación contra la Leucemia Josep Carreras (IJC) de la mano de la Generalitat de Catalunya. Es el primero de Europa en hacer investigación exclusiva sobre leucemia y otras enfermedades malignas de la sangre.

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Extraordinary doctoral prize for the thesis, “Clinico-biological characterisation of myelodysplastic syndromes with 5q deletion”

  • Mar Mallo

The Autonomous University of Barcelona doctoral programme has awarded the extraordinary doctoral prize for the thesis Clinico-biological characterisation of myelodysplastic syndromes with 5q deletion presented in June 2013 by Dr. Mar Mallo, from the Catalan Institute for Oncology/Germans Trias i Pujol Campus of the Josep Carreras Leukaemia Research Institute.

The doctoral thesis, entitled, Clinico-biological characterisation of myelodysplastic syndromes with 5q deletion is based on a compilation of three works published in prestigious international journals in the field of oncohematology. The main purpose of the thesis is to delve deeper into the genetic and clinical aspects of those myelodysplastic syndromes (MDS) which have as a cytogenetic alteration the deletion of the long arm of the chromosome 5 (5q‐). Various techniques in molecular cytogenetics are used to tackle this pathology.

The first of the papers was a study of more than 600 patients diagnosed as having MDS without 5q deletion through fluorescence in situ hybridisation (FISH) techniques. 5q deletion was observed in 6% of cases. These results are important because highly effective treatments exist for patients who present this cytogenetic alteration. 

  • Mar Mallo 2

The second paper is based on the study of the natural history of MDS with 5q deletion. The clinical and biological data of more than 500 patients were collated, making it possible to determine that the presence of a cytogenetic anomaly accompanied by 5q deletion does not have a significant effect on global survival rates but does have an impact on the progress of the disease into acute myeloid leukaemia.

The third paper was a genetic study of this disease by means of genome microarray studies and direct sequencing. The study was able to establish how the presence of an accompanying cytogenetic alteration is associated with non-response to treatment. Furthermore, the presence of mutations in the TP53 gene show a tendency to predict such a non-response to treatment.

This thesis has deepened our clinical, biological and genetic knowledge of MDS with 5q deletion and has helped the scientific community to understand the natural history of the disease a somewhat better. 

Anti-leukaemia immunotherapy

Immunotherapy works by strengthening the body’s own immune system so that it can eliminate cancerous cells naturally. The aim is for the immune system to attack the cancerous cells in the desired manner and to detect them if they come back and continue to act. 

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