What prompts two medical doctors, after six years of training and five years of specialisation, to pursue a PhD? It’s simple: translational medicine.
Research has always been a great passion for Csaba Fehér (b. Budapest, Hungary, 1979). Fehér became an internist at the Hospital Clínic in Barcelona in 2013. While working as a doctor on call for a hospital in Barcelona, he collaborated in clinical research at IDIBAPS on Clostridium difficile, a bacteria that can cause diarrhoea when the gut flora is disrupted by antibiotic therapy. “While studying papers on this bacteria and on microbiota, I realised I could not critically assess them, because I lacked the proper knowledge of statistical analysis and analysis of large data sets,” Fehér says. “I had to believe the authors’ conclusions, but that was not satisfactory to me.”
Hepatologist Elisa Pose (b. Santiago, 1987) also specialised at the Hospital Clínic.
She wanted to get involved in research to understand diseases better. “The lab offers you very helpful tools to do,” she says. At IDIBAPS, before joining IRB Barcelona, she worked on liver models based on biopsy samples from patients with acute-on-chronic liver failure, a serious deterioration of liver function in patients with cirrhosis, associated with failure of other organs and with a very poor prognosis. Now she wants to study RNA expression in patients with alcohol-related cirrhosis, analysing biopsies before and after years of abstinence. “We want to compare expression patterns to highlight those characteristic of the cirrhosis that disappear after alcohol withdrawal with those that do not.” To do this, they selected a group of patients and performed RNA sequencing on their biopsies to evaluate gene expression. But, to complete the job, she needs training in bioinformatics. “I want to understand which and how many genes are expressed and what function they have,” she explains, “and, most importantly, learn how to interpret all the data.”
Fehér and Pose have embarked on their PhD studies thanks to PhD4MD, a programme that aims to train a new generation of physician scientists to translate biomedical discoveries to patient treatments. PhD4MD is supported by two research centres, IRB Barcelona and CRG, and two hospitals, IDIBAPS and VHIR. Fehér and Pose, awardees in the programme’s second year in 2016, join Juan Miguel Cejalvo, the first PhD4MD fellow to join IRB Barcelona in 2015. The third call of the PhD4MD programme closed on 6 April.
Both Fehér and Pose now work in Patrick Aloy’s Structural Bioinformatics and Network Biology Lab at IRB Barcelona and split their time between the Institute and IDIBAPS.
Fehér is working on an ambitious project that he hopes will contribute to the development of an effective therapeutic vaccine for HIV. “People affected by HIV today have a comparable life expectancy to anyone else, but the price for this is a life-long obligation to take combined antiretroviral therapy daily, with all the toxicity, adherence difficulty, and costs that it entails,” he explains. “The idea is to find a way to ‘re-teach’ the immune system to fight the virus and control the viral load. This is difficult because the immune system’s CD4 cells themselves are the target of the virus.”
In the most successful clinical trial for such a vaccine so far, scientists at IDIBAPS used dendritic cells, key cells responsible for the immune system response, and autologous inactivated virus as the active ingredient of the vaccine. Unfortunately, the vaccine worked on only some patients, and it is not yet clear why. “In other diseases,” Fehér explains, “vaccination efficacy has been shown to be related to different transcriptomic factors.”
Fehér believes it’s worth examining whether this relationship is true for HIV, too. In a collaboration between IRB Barcelona, IDIBAPS, and the Erasmus Medical Center in Rotterdam, he is combining clinical, immunological and transcriptomics data sets to create a predictive model that can differentiate at an early stage individuals who will respond to the vaccination from those who will not. “This would allow us to identify patients who can safely stop antiretroviral treatment after vaccination and those who cannot,” he explains. “Patrick's lab was an excellent choice for this project because his group has huge experience in this kind of analysis.”
The research itself is not the only challenging part of the PhD process for Pose and Fehér. “First of all, time management is complicated,” says Pose. “I am in the hospital, in my lab at IDIBAPS and in my lab with Patrick: it’s not easy to combine all of this.” Fehér felt frustrated at the beginning because his fellow students mastered basic concepts that he had never seen in his academic career. “Beginning from scratch is difficult. We only had biology in our first year of university, and now we are all of a sudden among people who are experts in the field,” he says.
However, they have valuable assets that other PhD students do not. “We have a broader vision of other aspects that our colleagues here are less versed on,” Pose says. “For example, we know which scientific questions really matter for the clinic, and what doctors need.”
Both perspectives are key to the success of translational medicine. “Biomedical researchers and clinical researchers speak a different language,” notes Fehér, “but we need to learn how to communicate with each other if we really want to make a difference in biomedicine.” Pose agrees: “Breakthrough in biomedicine can only come from an alliance between labs and hospitals.”