Final Report Summary - INCOMED (INCOMING FELLOWSHIPS BIOMEDICINE INSTITUT DE RECERCA VALL D’HEBRON)
The INCOMED is an incoming mobility programme that promotes training and career development that complies with the concept of individual trans-national mobility. It is addressed to experienced researchers capable of developing a competitive research project and based on the merit of the candidates. INCOMED promotes 10 postdoctoral fellowships in all areas of biomedicine and clinical medicine at the Research Institute Vall d‘Hebron (IR-HUVH).
INCOMED published three calls offering a total of 10 fellowships. Each fellowship had a duration of maximum two years. Eligible candidates were invited for interviews and freely decided the research topic, destination and research group.
Following an accurate selection process a total of 8 incoming fellowships have been granted. The research areas covered gather identification of biomarkers in inflammatory diseases, Molecular Oncology, Advanced therapies for heart repair, Molecular mechanisms involved in brain tumors, Neuroprotection: Animal Models of Brain Ischemia, Apoptosis in nervous system, Molecular mechanisms in the pathogenesis of traumatic brain injury, Renal damage and regeneration, Myocardial protection against ischemic injury from cells to patients, Work-related diseases, asthma and fibrosis and HER2-driven metastasis in breast cancer.
a) Fellow 1. Prostate cancer is the most common cancer in men and the second leading cause of death for cancer in western countries. The current therapy for metastatic prostate cancer is based on chemotherapy. Though initially effective, most (over 90%) patients develop resistance and relapse.
During this project, was found a strong repressor of the tumor representing a good target for therapy of aggressive prostate cancer. If the project results are confirmed and validated in a significant cohort of patients, they might lead to the development of alternative therapeutic treatments, potentially more efficient and specific than actual ones. Thus, the results may impact on the high rate of mortality and the economic cost of our Health System.
b) Fellow 2. The incidence of ulcerative colitis (UC) in Spain has increased by ten-fold in 20 years. Dysbiosis in UC patients causes dis-regulation of the immune system, currently controlled with expensive immunosuppressive drugs. Patients with UC are characterized by an altered gut microbiome. The project isolated and sequenced bacterial DNA from UC patients and healthy donors to identify relevant bacteria necessary to build the cocktail. The results obtained during this fellowship allowed to develop all the tools (bacterial analysis, bacterial collection, animal and ex vivo human model) necessary to the success of the bacterial cocktail.
c) Fellow 3. Edometrial cancer (EC) is the most common gynaecological cancer in the western countries and the second most common gynaecological malignancy worldwide. Radical hysterectomy is the cornerstone therapy for EC. However, in high risk tumors, adjuvant chemotherapy, radiotherapy or a combination of both therapies is recommended. Currently, adjuvant treatments show limited response in patients with advanced disease, presenting also high toxicity. The main clinical challenge in EC research is to find biomarkers able to predict those patients that will recur and select a suitable treatment for them.
In this study were found evidences suggesting that the biomarker ANAX2 could be involved in the invasion ability of EC cells and in the ability of these cells to adhere to the ECM, altogether contribution to the progression and dissemination of EC. Less clear is the role of ANAX2 in the resistance of EC cells to chemotherapy.
d) Fellow 4. Breast cancer is the most frequently diagnosed neoplasm in women and a leading cause of cancer death. Breast adenocarcionomas show a wide spectrum of genetic and epigenetic alterations.
The principal aim of this project was the characterization of KLHDC7B protein function and its expression in metastatic breast cancer, which its alteration has been associated with cancer metastasis. The results derived from this project, propose KLHDC7B as a new marker of breast cancer, especially in metastasis stage and MDA-MB231 as a good cell line to study tumor heterogeneity and clonal cooperation.
e) Fellow 5. The use and misuse of antibiotics has accelerated the emergence of multi-resistant pathogenic strains in the last decades. Therefore, it is critical to investigate new types of antibiotics capable of halting the progression of resistant microorganisms.
In this project, experimental and theoretical fields were combined to develop an automated pipeline, written in R language. These results shed light on new therapeutic avenues to control the proliferation of antimicrobial resistance. In addition, they have the potential to identify new targets for drug action and to develop new molecules as antimicrobials. Both results are likely to be patented.
f) Fellow 6. The current project was focused on the acquisition of resistance in a small population of stem-like cells, known as cancer stem cells (CSCs). This population is thought to be responsible for tumor formation. Accordingly, relapse of cancer patients is due to the propagation and expansion of CSCs which are resistant or become resistant to conventional chemo- and radiotherapeutic treatments. As a result, more than 99% of death in cancer patients is due to acquisition of resistance by the tumoral cells, specifically the CSCs.
During this project were determined some mechanisms by which CSCs become resistant to chemotherapeutic treatments which include metabolic reprogramming and autophagy. For that part, was proposed that treatment with bactericidal antibiotics might represent a novel approach to target CSC as well as chemoresistant cancer cells. Therefore, one of the potential impacts of the project is to provide recommendation to the clinics as part of the appropriate trials.
g) Fellow 7. Aortic aneurysm (AA) is a frequent cardiovascular disease consisting in a pathological dilation of the wall of the aorta. AA leading to dissections or rupture are major diseases affecting the aorta and a common cause of premature deaths, ranking as high as the 15th cause of death in developed countries.
The aim of the present project was to investigate all these interrelated aspect through the use of 4D-flow MRI, an innovative magnetic resonance (MR) technique.
The results provided by this project are likely to be resonated in clinical guideline.
h) Fellow 8. During this fellowship was evaluated the incidence and etiology of bacterial, viral and fungal infection in lung allograft donors and the donor-to-host transmission of these infections. It was also, documented transmission of multidrug resistance bacteria and based on that if is necessary change antimicrobial prophylaxis. A results of this study showed that an appropriate prophylactic antimicrobial regime and modification according to the microorganisms isolated in donor and recipient cultures is key to avoid complications in lung transplant recipient.
This study promotes and enforces a rational use of antibiotics in immunosuppressed patients to avoid multidrug resistance.
INCOMED impact in the European Research Area as implementing a tool that allows experienced researchers to obtain professional training and career development in biomedicine and clinical medicine in a leading European University Hospital and Research Centre.
http://www.vhir.org/larecerca/INCOMED/INCOMED_presentacio.asp?mv1=2&mv2=7&mh1=2&mh2=7&mh3=4&cont=1&Idioma=ca(se abrirá en una nueva ventana)
INCOMED published three calls offering a total of 10 fellowships. Each fellowship had a duration of maximum two years. Eligible candidates were invited for interviews and freely decided the research topic, destination and research group.
Following an accurate selection process a total of 8 incoming fellowships have been granted. The research areas covered gather identification of biomarkers in inflammatory diseases, Molecular Oncology, Advanced therapies for heart repair, Molecular mechanisms involved in brain tumors, Neuroprotection: Animal Models of Brain Ischemia, Apoptosis in nervous system, Molecular mechanisms in the pathogenesis of traumatic brain injury, Renal damage and regeneration, Myocardial protection against ischemic injury from cells to patients, Work-related diseases, asthma and fibrosis and HER2-driven metastasis in breast cancer.
a) Fellow 1. Prostate cancer is the most common cancer in men and the second leading cause of death for cancer in western countries. The current therapy for metastatic prostate cancer is based on chemotherapy. Though initially effective, most (over 90%) patients develop resistance and relapse.
During this project, was found a strong repressor of the tumor representing a good target for therapy of aggressive prostate cancer. If the project results are confirmed and validated in a significant cohort of patients, they might lead to the development of alternative therapeutic treatments, potentially more efficient and specific than actual ones. Thus, the results may impact on the high rate of mortality and the economic cost of our Health System.
b) Fellow 2. The incidence of ulcerative colitis (UC) in Spain has increased by ten-fold in 20 years. Dysbiosis in UC patients causes dis-regulation of the immune system, currently controlled with expensive immunosuppressive drugs. Patients with UC are characterized by an altered gut microbiome. The project isolated and sequenced bacterial DNA from UC patients and healthy donors to identify relevant bacteria necessary to build the cocktail. The results obtained during this fellowship allowed to develop all the tools (bacterial analysis, bacterial collection, animal and ex vivo human model) necessary to the success of the bacterial cocktail.
c) Fellow 3. Edometrial cancer (EC) is the most common gynaecological cancer in the western countries and the second most common gynaecological malignancy worldwide. Radical hysterectomy is the cornerstone therapy for EC. However, in high risk tumors, adjuvant chemotherapy, radiotherapy or a combination of both therapies is recommended. Currently, adjuvant treatments show limited response in patients with advanced disease, presenting also high toxicity. The main clinical challenge in EC research is to find biomarkers able to predict those patients that will recur and select a suitable treatment for them.
In this study were found evidences suggesting that the biomarker ANAX2 could be involved in the invasion ability of EC cells and in the ability of these cells to adhere to the ECM, altogether contribution to the progression and dissemination of EC. Less clear is the role of ANAX2 in the resistance of EC cells to chemotherapy.
d) Fellow 4. Breast cancer is the most frequently diagnosed neoplasm in women and a leading cause of cancer death. Breast adenocarcionomas show a wide spectrum of genetic and epigenetic alterations.
The principal aim of this project was the characterization of KLHDC7B protein function and its expression in metastatic breast cancer, which its alteration has been associated with cancer metastasis. The results derived from this project, propose KLHDC7B as a new marker of breast cancer, especially in metastasis stage and MDA-MB231 as a good cell line to study tumor heterogeneity and clonal cooperation.
e) Fellow 5. The use and misuse of antibiotics has accelerated the emergence of multi-resistant pathogenic strains in the last decades. Therefore, it is critical to investigate new types of antibiotics capable of halting the progression of resistant microorganisms.
In this project, experimental and theoretical fields were combined to develop an automated pipeline, written in R language. These results shed light on new therapeutic avenues to control the proliferation of antimicrobial resistance. In addition, they have the potential to identify new targets for drug action and to develop new molecules as antimicrobials. Both results are likely to be patented.
f) Fellow 6. The current project was focused on the acquisition of resistance in a small population of stem-like cells, known as cancer stem cells (CSCs). This population is thought to be responsible for tumor formation. Accordingly, relapse of cancer patients is due to the propagation and expansion of CSCs which are resistant or become resistant to conventional chemo- and radiotherapeutic treatments. As a result, more than 99% of death in cancer patients is due to acquisition of resistance by the tumoral cells, specifically the CSCs.
During this project were determined some mechanisms by which CSCs become resistant to chemotherapeutic treatments which include metabolic reprogramming and autophagy. For that part, was proposed that treatment with bactericidal antibiotics might represent a novel approach to target CSC as well as chemoresistant cancer cells. Therefore, one of the potential impacts of the project is to provide recommendation to the clinics as part of the appropriate trials.
g) Fellow 7. Aortic aneurysm (AA) is a frequent cardiovascular disease consisting in a pathological dilation of the wall of the aorta. AA leading to dissections or rupture are major diseases affecting the aorta and a common cause of premature deaths, ranking as high as the 15th cause of death in developed countries.
The aim of the present project was to investigate all these interrelated aspect through the use of 4D-flow MRI, an innovative magnetic resonance (MR) technique.
The results provided by this project are likely to be resonated in clinical guideline.
h) Fellow 8. During this fellowship was evaluated the incidence and etiology of bacterial, viral and fungal infection in lung allograft donors and the donor-to-host transmission of these infections. It was also, documented transmission of multidrug resistance bacteria and based on that if is necessary change antimicrobial prophylaxis. A results of this study showed that an appropriate prophylactic antimicrobial regime and modification according to the microorganisms isolated in donor and recipient cultures is key to avoid complications in lung transplant recipient.
This study promotes and enforces a rational use of antibiotics in immunosuppressed patients to avoid multidrug resistance.
INCOMED impact in the European Research Area as implementing a tool that allows experienced researchers to obtain professional training and career development in biomedicine and clinical medicine in a leading European University Hospital and Research Centre.
http://www.vhir.org/larecerca/INCOMED/INCOMED_presentacio.asp?mv1=2&mv2=7&mh1=2&mh2=7&mh3=4&cont=1&Idioma=ca(se abrirá en una nueva ventana)