VHIR is seeking a researcher to join the Research Group in Cardiovascular Diseases, to work on a project recently funded by the Spanish Science and Innovation Ministry (Ayudas a Proyectos en Líneas Estratégicas). More information about our group can be found at: .
Education and qualifications:
Required:
1. Degree in Biology, Biochemistry, Pharmacy, Biomedicine, Veterinary Medicine or a related discipline
2. Master’s degree
3. Accredited for animal handling
4. High academic marks (degree and master) are a must
5. Good communication skills and fluency in spoken and written English
Desired:
1. Strong sense of responsibility, initiative, self-motivation and social skills as key personal abilities
2. Ability to work independently
3. Previous publications
4. Research stages abroad
Experience and knowledge:
Required:
1. Good knowledge of animal physiology, especially in the cardiovascular system, will be positively valued
2. Good molecular biology background and experience in molecular biology techniques (Western Blot, PCR, immunofluorescence, etc.) will be positively valued
Desired:
1. Previous experience in research
Main responsibilities and duties:
1. To develop his/her own translational research project to solve an unmet clinical issue in cardiology. This includes conducting the appropriate experiments (both in vivo and in vitro animal models), data measurement and interpretation, and statistical analyses.
2. To join the research team and collaborate and support other research members in the development of their projects.
3. To generate a fruitful discussion within the group.
Labour conditions:
1. Full-time position: 40h/week
2. Contract length: 10 months, associated to a project funded by the Spanish Science and Innovation Ministry (Ayudas a Proyectos en Líneas Estratégicas)
3. Starting date: Immediate
4. Gross annual salary: 22.823,22€
5. Contract: Temporary
6. Project title: NC-p38i - Novel drug candidates to ameliorate cardiac injury induced by ischemia-reperfusion and by anthracycline.
Project Summary:
NC-p38i aims to deliver new compounds to ameliorate cardiac injury induced by ischemia-reperfusion and to protect cancer patients against the cardiotoxicity induced by chemotherapy, through a common mechanism. Cardiovascular diseases are the leading cause of death globally and entail one of the major economic challenges of public healthcare worldwide. Among them, ischemic heart disease is the most prevalent cardiovascular disorder and the most common cause of debilitating disease and death for the population over 65 years old in western cultures. The incidence rate of this particular disease increases significantly with age, and current therapies do not efficiently manage and reduce the damage associated with this condition. In this context, NC-p38i intends to explore the therapeutic potential of inhibiting specific functions of p38 MAPK in cardiomyocytes, which can lead to a variety of cardiovascular diseases, such as heart failure.
Cardiac muscle cell death is a common feature of both ischemia-reperfusion injury and chemotherapy-associated cardiotoxicity. These pathologies involve both oxidative stress processes and a specific mechanism of p38 MAPK activation that implies autophosphorylation. This alternative p38 MAPK activation pathway occurs mainly in cardiomyocytes, and inhibitors of p38 MAPK have been reported to reduce cardiomyocyte death both in vitro and in vivo. Despite the therapeutic potential associated with p38 MAPK inhibition, none of the developed inhibitors has progressed beyond phase II clinical trials due to low efficacy and undesirable effects. Most of the compounds that failed in clinical trials are ATP competitors, which suppress kinase activity, whereas targeting the alternative activation mechanism of p38 MAPK for therapeutic purposes has barely been explored.
Our previous work in this field allowed us to identify in silico and validate in biochemical assays several hits specifically targeting this alternative mechanism of p38 MAPK activation with high selectivity and good potency. Preliminary results using rat and human cardiomyocytes in culture suggest that these compounds reduce cell death induced by simulated ischemia-reperfusion and may display a cardioprotective role on doxorubicin-induced toxicity. However, these compounds showed some undesired toxicity in vivo. To address this issue, several new compounds were designed in silico and synthesized including modifications that maintain the ability to inhibit p38 MAPK autophosphorylation but did not show side effects in animals. In consequence, the present project intends to progress and finish the lead optimization phase. We will focus on the in vivo characterization of this new series of compounds that have the desired biochemical activity and display reduced toxicity in animals, using ex-vivo and in vivo models of cardiac diseases, including aged animals. In addition, further analogues will be designed, synthesized and tested to improve the potency and drug-like properties of the compounds. We aim at advancing the derisking of these new compounds having in mind its transfer to market, thus answering both unmet medical needs: ischemia-reperfusion injury and chemotherapy-induced cardiotoxicity.
What can we offer?
1. Incorporation to Vall d’Hebron Research Institute (VHIR), a public sector institution that promotes and develops biomedical research, innovation and teaching at Vall d'Hebron University Hospital (HUVH), the biggest hospital of Barcelona and the largest of Catalan Institute of Health (ICS).
2. A scientific environment of excellence, highly dynamic, where high-end biomedical projects are continuously developed.
3. Continuous learning and a wide range of responsibilities within a stimulating work environment.
4. Individual training opportunities.
5. Flexible working hours.
6. 23 days of holidays + 9 personal days.
7. Flexible Remuneration Program (including dining checks, health insurance, transportation and more).
8. Corporate Benefits platform through which you can obtain significant discounts on travel, culture, technology, gastronomy, sports, among many others.
9. Healthy Offering: choose from a variety of wellbeing focused activities to be the healthiest you.
Deadline to apply: 27/02/2025
VHIR embraces Equality and Diversity. As reflected in our values, we work toward ensuring inclusion and equal opportunity in recruitment, hiring, training, and management for all staff within the organization, regardless of gender, civil status, family status, sexual orientation, gender identity and expression, religion, age, functional diversity or ethnicity.
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