VHIO Presents 10 Research Proposals for Incoming ”la Caixa” Doctoral INPhINIT Fellowships
Ten early-stage researchers have the opportunity of starting a top scientific career @ VHIO, Severo Ochoa Centre, under ”laCaixa” Doctoral INPhINIT Incoming Fellowship programme, and boost their careers.
Decide which VHIO INPHINIT PhD Project fits better your research interests and APPLY through "la Caixa" application portal
In addition to financial support, the programme offers a 3-year employment contract and additional funding for conferences, courses, research stays, consumables, equipment, charges for the use of intellectual property, etc ; the fellowship includes a training programme in transversal skills such as entrepreneurship, technology transfer, intellectual property, leadership, creativity, communication, teamwork, personal development, planning, assertiveness and networking.
The final results will be published on the ”la Caixa” Foundation website on June 8, 2023.
More Information and Application:
Programme rules – Doctorate INPhINIT Incoming (PDF)
Retaining ”la Caixa” Doctoral INPhINIT Fellowships
This frame is addressed to any discipline and any university or research center in Spain or Portugal. Candidates must have resided or carried out their main activity (work, studies, etc.) in Spain for more than 12 months in the 3 years immediately prior to the call deadline. All the VHIO labs are open to host candidates through the Retaining frame. APPLY HERE
Deadline for submitting applications 16 February, 2023.
Characterizing the role of GDF15 in breast cancer therapeutics | Josep Villanueva, PhD
The characterization of the molecular mechanisms adopted by tumor cells to communicate with their microenvironment during therapeutic treatment is essential to understanding tumor response and resistance to cancer drugs. Our laboratory has specialized in investigating the cancer secretome by quantitative proteomics and, we have developed experimental and data analysis methodology for the high-throughput study of the secretome of tumor cells. We have also applied the secretome framework to different cancer-related projects, including the development of candidate pharmacodynamic biomarkers for the response of cancer drugs, and the characterization of a new signaling pathway in Triple-Negative Breast Cancer (TNBC) associated to tumor invasion and metastasis. During the course of a recent project aimed at the identification of biomarkers linked to the action of a new chemotherapeutic agent in breast cancer, we identified Growth Differentiation factor 15 (GDF15) as being over-secreted in tumor cells responding to the drug. GDF15 belongs to the TGFβ family, and plays a key role in the establishment and maintenance of cachexia in advanced cancer patients. Our results demonstrate that GDF15 is also over-secreted in a metastable cell population, known as drug-tolerant persister (DTP), which initially survives the action of chemotherapy and enters into quiescence. Despite its biomarker potential for chemotherapy response, our results show that GDF15 is also paradoxically required for survival of DTP cells. The project offered here is aimed at characterizing the role of GDF15 in TNBC therapeutics, and to study the molecular mechanisms used by DTP cells to become fully resistant to cytotoxic cancer drugs.
JOB POSITION DESCRIPTION
The ideal candidate would be a highly motivated, ambitious student with a strong background in molecular biology and/or biochemistry. A keen interest in protein biochemistry and cancer therapeutics would be desirable. Laboratory experience, especially with the standard molecular and cellular biology techniques would also be greatly valued. The successful candidate is expected to work closely with other team members, have excellent communication skills, organizational and time-management skills, and an inquisitive mind.
Dissecting the interaction between tumor and immune cells after treatment with PARP inhibitors and platinum drugs in breast cancer | Violeta Serra, PhD
The group of Experimental Therapeutics led by Dr. Serra has a unique expertise of conducting hypothesis-based targeted therapy research in breast cancer. This group uses a multidisciplinary strategy by working with oncologists and bioinformaticians, among others, and develops novel approaches to better understand the mode of action of novel therapies as well as identify new response biomarkers. Dr. Serra’s lab is embedded in VHIO, which has long history of cutting-edge research in cancer therapy and guarantees access to multiple molecular, genetic and biochemical technologies. Noteworthy, in VHIO there is an already established pipeline that allows to apply translational research to in-vivo and ex-vivo studies by using patient material from VHUH. This lab is currently composed of a principal investigator, an associate researcher, a pathologist (part-time), five PhD students, two technicians and one visiting student.Among other achievements, Dr. Serra’s group developed an assay to predict response to treatment in patients harboring BRCA1/2-mutated tumors and ultimately, guide the optimal sequential therapies. Despite the success of platinum-based drugs or poly (ADP-ribose)-polymerase inhibitors (PARPi) in eradicating BRCA1/2- deficient cells, 40% of metastatic breast tumors display intrinsic resistance and a major fraction of the sensitive ones eventually progress. Hitherto, the most well described mechanism that frequently drives intrinsic and acquired resistance in BRCA1/2-deficient tumors is through the restoration of error-free Homologous Recombination Repair (HRR). The test developed by this research group is based on the detection of RAD51 nuclear foci formation, which captures HRR functionality in a dynamic manner. Unlike tumor sequencing tests or genomic scars currently used in the clinical practice, the RAD51 test has proven to be highly discriminative of PARPi sensitivity versus resistance in both BRCA1/2-mutant PDX models and patient samples.
JOB POSITION DESCRIPTION
This PhD position consists in integrating genetic/genomic, molecular and immune biomarkers to better understand the mechanism of action and resistance to DNA-damaging drugs, including PARPi. Tumors with defective DNA repair by the HRR pathway harbor chromosomal instability resulting from unrepaired DNA damage and leading to activation of the cyclic GMP–AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, which stimulates the anti-tumor immune response via the Type 1 Interferon (IFN-I) axis. STING pathway suppression has been suggested as an immune escape mechanism; thus, STING agonists (STINGa) have been developed to enhance anti-cancer effects. Dr. Serra’s group is studying the impact of STING pathway activation in PARPi antitumor response using patient-derived tumor xenograft (PDX) models. Follow up studies embedded in this PhD project will help dissect the innate vs. adaptive immune responses involved in the PARPi response.The main tasks will include the design and execution of experiments, management and analysis of mouse models and patient samples to study the immune response after treatment with DNA-damage related drugs, including FACS, single-cell sequencing, immunoblotting or immunohistochemistry. To carry out these tasks will require a broad literature research, enrolling to courses offered by the PhD program and attending lectures and webinars from renowned scientists in the field of immune-oncology. VHIO supports continuing education including language courses and the Course in Training Research Staff Users of Animals for Experimentation, which is essential to work with mice. In addition, this job position will also demand high communication and writing skills to present the data in scientific seminars, workshops or conferences, and to establish solid collaborations both national and international, as well as to publish the data on high impact factor scientific journals.
Microbiota composition as risk predictor in cancer patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) | Paolo Nuciforo, MD, PhD
The estimated billions of bacteria and other microorganisms that inhabit the human body, collectively called the microbiota, establish an ambivalent relationship with the host that, in physiological situations, provides benefits such as a proper functioning of the immune system. Microbiota from different compartments (mainly the gut) appears in a state of dysbiosis that can promote an increase in the individual’s vulnerability to external factors such as viral infections. Recent studies carried out in patients with different types of cancer infected by COVID-19 suggest that cancer patients have a higher risk of contracting the virus and a more unfavorable clinical course compared to the general population. Preliminary evidence suggests that imbalances in gut microbiome composition could be associated with COVID-19 severity and persistence in non-cancer patients. However, there is no published research regarding COVID-19 disease and the study of the microbiota in cancer patients. The main hypothesis of our study is that, in cancer patients, the pre-existing dysbiotic state induced by the tumor and/or specific treatments could favor COVID-19 infection and a worse prognosis through the induction and/or maintenance of an immunosuppressive state. Our study’s main objective is to investigate the composition of the microbiota in cancer patients with COVID-19 through DNA sequencing in stool and saliva samples collected at different times during the evolution of the infection. The results obtained will be compared with those derived from cohorts of cancer patients without COVID-19 infection in order to establish whether there is a direct relationship between COVID-19 infection, and how this interrelation affects the clinical course of the cancer patient. Furthermore, our results could allow the identification of microorganisms or microbial profiles that are predictive of complications and actionable, and provide more data on the behavior of COVID-19 in cancer patients.
JOB POSITION DESCRIPTION
We are looking for a highly motivated and talented PhD candidate with a clear dedication to research impacting patient care. The candidate will take an active role in the research project, designing, planning and performing the research in the Molecular Oncology Group under the supervision of the team leader Paolo Nuciforo. The candidate will work in a multidisciplinary team of oncologists, pathologists, molecular biologists, research nurses, epidemiologists, and bioinformaticians. Research project tasks will include (but not limited to) study data and sample acquisition, sample processing (DNA extraction for 16S RNA gene sequencing, aliquoting for storage, …), perform molecular tests (PCR, ISH, …), data analysis, interpretation and presentation both to internal and international meetings, maintain knowledge on research topic (through bibliography search). The applicant should be able to work independently, but also to be a team player and be willing to contribute to the team’s success. Excellent English writing and oral skills are required.
Mining the molecular determinants of the personalized antitumor T-cell response in cancer patients to develop more effective immunotherapies | Alena Gros, PhD
Cancer immunotherapy attempts to mobilize the immune system to recognize and kill cancer cells. T lymphocytes play an important role in the efficacy of this therapeutic approach. Tumor-specific TCR and pMHC ligand discovery are essential for understanding and manipulating immune responses to tumors. However, the high diversity and private nature of the TCR repertoire challenge our ability to monitor and exploit tumor-specific T cells in cancer patients. Identification of antitumor lymphocytes in blood has tremendous therapeutic potential, but it is further complicated by their lower prevalence. On the other hand, unique antigens presented by unique HLA alleles expressed by tumor cells defy the discovery of new targets for immunotherapy.
Given the Tumor Immunology and Immunotherapy group’s interest in understanding existing immunotherapies and developing novel T-cell based therapies, the PhD candidate will be involved in:
Objective 1: Characterizing the transcriptomic, phenotypic and TCR clonotype landscape of circulating lymphocytes at the single cell level in peripheral blood of cancer patients.
Objective 2: Identifying the personalized tumor antigens recognized by T cells via a high throughput genetic-based immunological screening platform.
Overall, we aim provide a better understanding of the dynamics of anti-tumor T-cell responses in patients treated with immunotherapy and the personalized antigens driving effective antitumor responses. More importantly, together with our clinical collaborators at VHIO, we are committed to translating the findings derived from this work into new therapies.
JOB POSITION DESCRIPTION
The Tumor Immunology and Immunotherapy Group of the Vall d’Hebron Institute of Oncology (VHIO) is seeking a highly motivated and team-oriented individual. The candidate will become part of an international team of scientists working in close collaboration with clinicians and dedicated to the development of personalized immunotherapies. The selected candidate will be involved in a project studying the personalized antitumor T-cell response in cancer patients using single cell multi-omics. Strong background in the tumor immunology and immunotherapy field with prior experience working with T-cell cultures and using multicolor flow cytometry as well as single cell transcriptomic analysis and interpretation is preferred. She/he should know how to work independently and have strong analytical skills, in addition to creativity, curiosity, enthusiasm, excellent communication skills and ability to work in a team. Fluency in spoken and written English is required.
Multi-omics liquid biopsy for monitoring tumor evolution and drug resistance in prostate cancer | Joaquín Mateo, MD, PhD
Molecular profiling of tumors is central to the development of personalized cancer medicine. Liquid biopsies allow for non-invasive monitoring tumor genomic and transcriptomics evolution. Our group is developing novel approaches for integrating multi-omics data from ctDNA, tumor extracellular vesicles (tEV) and circulating tumor cells (CTC) that can be found in the blood from patients with advanced prostate cancer. We want to further study how these analytes change with tumor evolution. In this project, we will leverage a collection of patient-derived xenografts (PDX) derived by our team from metastatic prostate cancer biopsies – we will expose this PDX to systemic anticancer therapy and study the kinetics of ctDNA, tEV and CTC in plasma, pursuing also genomics and transcriptomics assays, and studying CTCs as response biomarkers and drivers of drug resistance. We aim to further understand the distinct features of these analytes and their complementarity as clinical biomarkers. We will develop integrative multi-omics signatures to be validated in plasma samples from metastatic prostate cancer patients treated in clinical research studies at our center. Available tumor genomics and transcriptomics data for these same patients will allow for correlative liquid-tissue biopsy analysis.
The Prostate Cancer Lab at VHIO is a multidisciplinary research group encompassing expertise in clinical research, molecular biology, genomics and computational oncology. Our research follows a bench-to-bedside-and-back model; we interrogate preclinical models, patient-derived models, and patient samples for a comprehensive development of new therapeutics and biomarkers that can accelerate precision medicine strategies for prostate cancer patients. In the last years, we have set up a biobank with longitudinal plasma sample from prostate cancer patients, with clinical and treatment data for correlative analysis, as well as a platform of PDX derived from biopsies of the same patients.
JOB POSITION DESCRIPTION
We are looking for a motivated PhD candidate with a background either in biomedical sciences, biotechnology and/or computational biology who wants to work in a multidisciplinary team and with a clear bench-to-bedside-and-back philosophy, aiming for our research to impact patient care. The project can be adapted for a candidate with wet-lab, computational or mixed interests/skills. The candidate is expected to work in close collaboration with clinical, translational and basic researchers to gain a comprehensive view of cancer research. The fellowship is to be carried out at the Vall d’Hebron Institute of Oncology (VHIO). VHIO is a leading comprehensive cancer research center integrated in the Vall d’Hebron University Hospital Campus in Barcelona. The call is for a full-time position; the project and laboratory training will be complemented with a comprehensive educational program of internal and external courses and conferences aiming for the candidate to become a future leader in cancer translational researcher. The program will be developed together with the fellow and the VHIO Academy Office, to suit their specific career development needs.
In this proposal, the applicant will be expected to complete a PhD and submit a thesis by the end of the fellowship. The thesis will be co-directed by Joaquin Mateo (team leader) and Irene Casanova (senior postdoc), who will combine their complimentary expertise to supervise and support the applicant during their PhD. The candidate will be supported by our bioinformatics core and other investigators in the group. Beyond their thesis, we expect the candidate to publish their research in scientific journals and present their results at international conferences during the the fellowship.
VHIO adheres to the EU Commission Human Resources Strategy for Researchers (HRS4R) code to ensure the highest standards in recruitment and development of research careers.
PhD position at the Experimental Hematology lab to study immunopathogenesis in blood cancers | Francesc Bosch, MD, PhD
The Experimental Hematology group, directed by Dr. Francesc Bosch, head of the Hematology Department at Vall d’Hebron University Hospital, focuses on the study of the mechanisms of pathogenesis and progression of hematologic malignancies. We are a highly multidisciplinary group where both clinicians and basic scientists are involved in the design and execution of the research projects. Our main purpose is to translate preclinical findings into clinical benefit through the development of early phase clinical trials and defining new prognostic and predictive factors.
Main research lines currently are:
Deciphering the mechanisms involved in pathogenesis and progression of hematological neoplasias.
The preclinical study of new therapeutic regimens in experimental models that mimic the tumoral immune microenvironment.
Defining new biomarkers for a more rational and precise treatment of patients.
JOB POSITION DESCRIPTION
We are looking for an enthusiastic predoctoral research scientist with a background in biomedicine and immunology to join our group. The research project to be developed is aimed at the study of the role of the immune system in lymphoid malignancies ex vivo and in vivo models that include patient-derived xenografts.
Study of the Immunosuppressive Tumor Microenvironment in Brain Cancer | Joan Seoane, PhD
Some cancer patients respond to immunotherapy with robust and durable responses. However, not all patients benefit from immunotherapy and the determinants of response to this type of treatments are still not known. Brain metastasis and glioblastoma are devastating diseases that share the same niche, the brain parenchyma. Importantly, melanoma and lung brain metastasis exhibit a worse response to immunotherapies than the corresponding extracranial lesions. Moreover, recent immunomodulatory approaches to tackle glioblastoma have been hampered by the immunosuppressive environment of these tumors. Our proposal aims at studying the brain tumor microenvironment in order to understand its impact on immunotherapy. We expect to identify biomarkers of response to immunotherapy and discover immunomodulatory factors that could be novel therapeutic targets. We will also assess if the characterization of the cerebrospinal fluid can be used to obtain information of the immune cell infiltrates in the brain tumor sparing invasive surgical procedures. Our specific objectives are: 1- Molecular characterization of brain metastases from lung and melanoma tumors, and glioblastoma. 2- Molecular characterization of cerebrospinal fluid samples. 3- Identification of potential therapeutic targets involved in the resistance to immunotherapy. 4- Functional validation of the therapeutic candidates through patient-derived models. We will use patient-derived models to develop our objectives in order to get as close as possible to the reality of the patient. We expect to identify novel therapeutic targets that could lead to efficacious therapies to tackle brain cancer and improve the life of brain cancer patients.
JOB POSITION DESCRIPTION
We are looking for highly motivated, talented, science-passionate PhD student candidates that want to work in a multidisciplinary team with a bench-to-bedside-and-back philosophy, aiming to impact patient care. The PhD student will take an active role in the research project both intellectually and experimentally, designing, planning and developing the project with the help of the supervisor or lab colleagues. The candidate will be able to learn a large number of techniques from in vitro biochemical methods to physiological in vivo studies including the study of the molecular mechanisms of action of therapeutic compounds through the analysis of samples from patients in clinical trials. Most of the research will be performed using patient-derived models in close collaboration with clinicians.The applicant should be able to work independently, but, most importantly, also be a team player willing to contribute to the team’s success.The project will be complemented with a comprehensive educational program of courses and conferences aiming for the candidate to become a future leader in translational research. PhD students are expected to present their work in English both within the research group and in international meetings. Excellent English writing and oral skills are required.
Transcriptional rewiring in KIT/PDGFRA oncogenic program for resistance to targeted agents. | César Serrano, MD, PhD
We aim to understand cancer evolution after targeted selective pressure of key drivers of cancer. Oncogenic programs are thought to be critically conserved throughout the entire course of the disease giving their biological relevance for tumor cell survival. However, scape mechanisms do exist, particularly in poorly understood populations such as heavily pre-treated patients, in which re-wiring of driver’s transcriptional programs emerges as a novel concept of drug resistance. To do so, we use gastrointestinal stromal tumor (GIST) – a paradigmatic model of oncogene addiction in solid tumors – and other tumor sharing similar biological principles. Our group has performed WES and RNAseq studies identifying such patients. This project will aim to undertake: 1) bioinformatics analysis to dissect the rewiring of KIT transcriptional network and uncover novel main players; 2) generation of CRISPR and patient-derived cellular and mice models (some of them already generated) to functionally study the relevance of this transcriptional rewiring; 3) identify novel drugs and therapeutic strategies to be translated into the clinic. We are a translational group devoted to the study of the biology of sarcoma with a big emphasis in translational oncology. The head of the group is César Serrano MD PhD, who has the dual role as Group Leader and Medical Oncology. Seven other people compose a multidisciplinary research group, which includes one postdoc, one bioinformatician, 3 PhD students, one student and one senior technician. Withing this team and research field, our investigation ranges broad fields of biology, being currently more focused tumor microenvironment, chromosome instability and protein degradation. Regardless, most of our projects are clearly patient-oriented and, for instance, two clinical trials have been started in the past five years thanks to the research performed in our laboratory.
JOB POSITION DESCRIPTION
We aim to incorporate a brilliant PhD student who will aim to advance the abovementioned research line in our laboratory. We also expect from him/her to engage in the scientific discussions that we commonly have, as the science that we do are not independent projects, but rather they focus on different aspects of the biology within a common interplay. Therefore, the PhD student will be certainly exposed during the PhD to a wide range of techniques and fields of knowledge, which ranges from molecular and cell biology, to bioinformatics, preclinical validations and engaging clinical discussions. Last but not least, the atmosphere of the lab is cool and we expect to maintain it or even improve it (if possible!).
When targeted therapies meet the immunotherapies | Teresa Macarulla, MD, PhD
Noncolorectal Gastrointestinal cancers (GI cancers) are a significant public health problem. Current conventional therapeutic options, such as surgery, chemotherapy, radiotherapy, and targeted therapies, are not always highly effective in noncolorectal GI cancer patients, and the overall mortality remains a major issue. Our group, led by Dr Teresa Macarulla (M.D. Ph.D.), is interested in seeking novel therapeutic strategies and associated predictive factors of noncolorectal GI cancers. One of our approaches is to combine biomarker discoveries and drug efficacy studies to better stratify noncolorectal GI cancer patients for personalized treatment. Our clinical team has actively participated in developing molecular therapies targeting altered signaling pathways of pancreatic, gastric, and bile duct cancers (cholangiocarcinoma), among others. We have contributed to multiple phases I-III clinical trials examining novel anti-cancer strategies against noncolorectal GI cancers. Notably, the U.S Food and Drug Administration and the European Medicines Agency have approved several tested molecules for clinical use. Moreover, using cancer patient-derived in vivo and ex vivo models, our preclinical team led by Dr Tian Tian (M.D. Ph.D.) is also studying the epigenetic and transcriptional features that can be used in gastric, pancreatic, and bile duct cancer diagnosis and treatment.
JOB POSITION DESCRIPTION
Ph.D. fellow will work on a project aiming to understand the diversity of cholangiocarcinoma (CCA) tumor microenvironment and design the next-generation of immunotherapy. Cholangiocarcinoma (CCA) is the second-most common hepatobiliary malignancy (accounting for ~15% of all primary liver cancers) and remains incurable (5-year survival rate, 7–20%). CCA is a highly heterogeneous tumor, and its complex cellular composition could explain its resistance to treatment and poor prognosis. How do CCA cells relate to the immune microenvironment? Does this relationship contribute to the previously reported low success rate of CCA immunotherapy? These questions need to be urgently addressed. Somatic mutations are frequently found in CCA patients. However, the functional impacts of these mutations on the CCA tumor microenvironment are still unknown. In this project, we will use state-of-the-art multiplexing techniques and high-throughput multimodal sing-cell technologies to study the tumor microenvironment in CCA patient samples. Moreover, we will also perform functional studies using patient-derived in vivo and ex vivo models.
Whole genome sequencing as a first-tier test to improve hereditary breast/ovarian genetic diagnosis | Judith Balmaña, MD, PhD & Sara Gutierrez-Enríquez
Despite advances in DNA sequencing technology enabling a multigene panel testing, no pathogenic variants in common breast/ovarian cancer susceptibility genes are identified in most screened individuals at risk. Whole genome sequencing (WGS) is an alternative test that would increase the diagnostic yield by detecting pathogenic variants in usually unscreened intronic regions as well as structural variants that may be underestimated with multigene targeted exon panels. We seek to demonstrate the WGS utility for identifying pathogenic variants in individuals with clinically defined hereditary breast/ovarian cancer syndrome. To achieve this goal, we will do: (i) a comparison of the diagnosis yield between WGS and standard-of-care genetic screening based on gene exon targeted panel in a prospective cohort of 250 cases; (ii) an accurate detection of spliceogenic deep intronic variants with an optimized in silico algorithm integrating and visualizing computational predictions; and (iii) an economical evaluation of the cost-effectiveness of introducing WGS into the clinical practice. The results will have direct and immediate application in the diagnosis and genetic counselling of patients and their families increasing the number of individuals that can benefit of personalized cancer treatments and cancer surveillance or prevention programs. The Hereditary Cancer Genetics Group is interested in unravelling the challenges of implementing the advances in genetic diagnosis of hereditary cancer susceptibility to clinical practice, through clinical and laboratory related research. Currently, the laboratory group includes one senior investigator, one associate investigator, a post-doc fellow and two predoc fellows. The clinical group has two medical oncologists, two genetic counsellors, one nurse, and one project manager.
JOB POSITION DESCRIPTION
The tasks of the predoctoral investigator will be:
-Setting informed consent preparation and approval.
-DNA collection, whole genome sequencing and variant prioritization
-Development and optimization of the web tool to prioritize deep intronic variant
-Yield comparison: standard testing vs whole genome sequencing
-Variant interpretation, classification, and confirmation with orthogonal approaches.